MXPA00010374A - Pyrrolidines as inhibitors of neuraminidases - Google Patents

Abstract

Disclosed are compounds of formula (I) which are useful for inhibiting neuraminidases from disease-causing microorganisms, especially, influenza neuraminidase. Also disclosed are compositions and methods for preventing and treating diseases caused by microorganisms having a neuraminidase, processes for preparing the compounds and synthetic intermediates used in these processes.

Description

PYRROLIDINAS AS INHIBITORS OF NEURAM INIDASAS Technical field The present invention relates to novel compounds, compositions and methods for the inhibition of neuraminidases, especially influenza neuraminidases. The invention also contemplates a composition and methods for the prevention and treatment of an influenza infection, as well as the processes for making said compounds and the synthetic intermediates employed in these processes.

BACKGROUND OF THE INVENTION Many of the microorganisms that cause diseases contain a neuraminidase (also known as sialidase) that is involved in the process of replication of the microorganism. In particular, viruses of the orthomyxovirus and paramyxovirus groups contain neuraminidases. Diseases associated with paramyxoviruses include RSV (diseases related to respiratory syncytial virus), pneua and bronchiolitis (associated with paramyxovirus type 3) and laryngotracheobronchitis (associated with paramyxovirus type 1). Some of the microorganisms that cause more important diseases in man and / or in animals that contain Neuramtnidases include Vibrio cholerae, Clostridium perfringens, Streptococcus pneuae, Arthrobacter sialophilus, influenza virus, parainfluenza virus, mumps virus, Newcastle disease virus, bird pest virus, equine influenza virus and the Sendai virus Mortality due to influenza is a serious problem throughout the world. The disease is devastating in humans, lower mammals and some birds. While there are vaccines containing attenuated influenza viruses, such vaccines only offer immune protection against a few strains of influenza and are less effective in populations with other types of immune compromise, such as populations of young children, the elderly and those who They suffer from a chronic respiratory disease. The loss in productivity due to absenteeism due to illness caused by an infection with the influenza virus has been estimated at more than 1 billion per year. There are two important strains of influenza virus (called A and B). Currently, there are only a few pharmaceutical products approved for the treatment of influenza. These include amantadine and rimantadine, which are only active against strain A of influenza viruses, and ribavirin, which has a dose-limiting toxicity. The mutant viruses resistant to amantadine and rimantadine appear rapidly during treatment with these agents. Neuraminidase is one of two important viral proteins protruding from the envelope of the influenza virus During the release of the progeny of the virus from the infected cells the neuraminidase diva the terminal residues of sialic acid glycoproteins the glycolipids and the oligosaccharides present on the cell surface The inhibition of the enzymatic activity Neuraminidase leads to the aggregation of progeny of the virus on the surface. These viruses are unable to infect new cells and therefore retard or block viral replication. X-ray crystallographic studies and sequence alignments have shown that the residues that make contact directly with the sialic acid portion of the substrate are strictly conserved in the neurammidases of all strains of influenza A and B Therefore a compound that binds to the binding region of the sialic acid of the active site of neuraminidase will block the replication of both strains of influenza A and B viruses These which are inhibitors of influenza neuraminidases will be useful in the prevention of an influenza infection and will be useful in the treatment of an influenza infection. The following references describe derivatives of neuraminic acid with the corresponding utility mentioned after each reference L Von Itzstein et al, European Patent Application No. EP539204 published April 28, 1993 (antiviral agent) T Honda et al European Patent Application No. EP823 28 published February 1, 1998 (sialidase inhibitor, influenza treatment), Honda T, et al, International Patent Application No. W098 / 06712, published February 19, 1998 (sialidase inhibitor, remedy for influenza), L Von Itzstein, et al, International Patent Application No. WO95 / 20583, published August 3, 1995 (viral neurammidase inhibitor, influenza treatment), P Smith, International Patent Application No. WO95 / 18800 , published July 13, 1995 (viral neuraminidase inhibitor), P Colman, et al, International Patent Application No. WO92 / 06691, published April 30, 1992 (viral neuraminidase inhibitor), L Von Itzstein, et al, U.S. Patent No. 5,648,379, filed on May 15, 1992. July, 1997 (treatment of influenza), P Reece, et al, International Patent Application No. W097 / 32214, published September 4, 1997 (binds to the active site of influenza virus neuraminidases), and P Reece , et al, International Patent Application No. W098 / 21243, published May 23, 1998 (anti-mfluenza agent) In the following references sialic acid derivatives are described with the corresponding utility mentioned after each reference and Ohira, et al. al, International Patent Application No. WO98 / 1 1083, published March 19, 1998 (antiviral agent), And Ohira, European Patent Application No. EP882721 published December 9, 1998 (antiviral agent), and B Glanzer, et al, Helvética Chimica Acta 74. 343-369 (1991) (inhibitor of Vibrio cholerae neuraminidase) In the following references describe benzene derivatives, cyclohexane derivatives or cyclohexene derivatives with the corresponding utility mentioned after each reference And Babu, et al, U.S. Patent No. 5,602,277, filed February 1, 1997 (neurammidase inhibitors), M Luo, et al, U.S. Patent No. 5 453 533, filed on September 26, 1995 (influenza neuraminidase inhibitor, influenza treatment), Y Babu, et al, International Patent Application No. WO96 / 30329, published October 3, 1996 (neuraminidase inhibitor, treatment of viral infection) , N Bischofberger, et al, U.S. Patent No. 5,763,483, filed June 9, 1998 (neuraminidase inhibitor), and K Kent, et al, International Patent Application No. 98/07685, published February 26, 1998 (intermediates for the preparation of neuraminidase inhibitors), C Kim, et al, International Patent Application No. W098 / 17647, published on April 30, 1998, describes pipepdine derivatives that are useful as neuramimase inhibitors N Bischofberger, et al, International Patent Application No. W096 / 26933 published September 6, 1996, describe various 6-membered substituted ring compounds which are useful as neuraminidase inhibitors The following references describe dihydropyran derivatives which are useful as inhibitors of viral neuraminidases: D. Andrews, et al. , International Patent Application N °: WO97 / 06157, published February 20, 1997; and P. Cherry, et al. , International Patent Application No.:W096/36628, published November 21, 1996. C. Kim, et al. , U.S. Pat. U U No. 5,512,596, filed April 10, 1996, describes aromatic derivatives in 6-membered rings which are useful as inhibitors of neuraminidases.

G. Diana, et al. , International Patent Application No. WO98 / 03487, published January 29, 1998, describe substituted pyridazines which are useful for the treatment of influenza. 15 B. Horenstein, et al. , International Patent Application No.: WO99 / 06369, published February 1, 1999, describe piperazine derivatives that are useful as neuraminidase inhibitors. Y. Babu, et al. , International Patent Application No.:20 W? 97/47194, published on December 18, 1997, describe substituted cyclopentanes which are useful as neuraminidase inhibitors and in the treatments for influenza. L Czollner, et al. , Helvética Chimica Acta 73_ 1338-1358 (1990) describe pyrrolidine analogs of neuraminic acid which are useful as inhibitors of Vibrio cholerae syllables.

The following references describe analogues of siastatin B which are useful as neuraminidase inhibitors: Y. Nishimura, et al. , Natural Product Letters 1 39- 4 (1992); and Y. Nishimura, et al. , Natural Product Letters 1 33-38 (1992). C. Penn, UK Patent Application No.:G B2292081, published February 14, 1996, describe the use of a neuraminidase inhibitor in combination with an influenza vaccine.

One of the objects of the invention is to provide compounds that inhibit the neuraminidases of microorganisms causing diseases; especially, viral neuraminidases; and, more especially, influenza neuraminidases. An object of the invention is also to provide compounds that inhibit the neuraminidases of influenza A and B strains. Another object of the invention is to provide a prophylaxis for an influenza infection in humans and other mammals. Another object of the invention is to provide a treatment for an influenza infection in humans and other mammals. Another object of the invention is to provide compounds that exhibit activity with influenza A virus and influenza B virus by inhibiting influenza neuraminidases when said compounds are administered orally. Another object of the invention is to provide a compound that can be transported effectively from the plasma to the bronchoalveolar fluid of the lungs of humans and other mammals in order to block the replication of the influenza virus in said tissue.

Description of the invention The present invention describes compounds possessing Formula I: I or a salt, an ester or an acceptable prodrug for pharmaceutical use thereof, wherein R1 is selected from the group consisting of (a) -C02H, (b) -CH2CO2H, (c) -SO3H, (d) -CH2SO3H, (e) -S02H, (f) -CH2SO2H, (g) -PO3H2, (h) -CH2P03H2, (i) -PO2H, 0) -CH2PO2H, (k) tetrazolyl, (I) -CH2-tetrazolyl, (m) ) -C (=?) - NH-S (0) 2 -R11, (n) -CH2C (= 0) -NH-S (0) 2 -R1 i, (o) -S02N (T-R11) R12 and (p) -CH2S02N (TR, 1) R12 where T is selected from the group consisting of (i) a bond, (ii) -C (= 0) -, (iii) -C (=?) 0-, ( iv) -C (=?) S-, (v) -C (0) N R36, (vi) -C (= S) 0-, (vii) -C (= S) S- and (viii) - C (= S) N R36-, R1 1 is selected from the group consisting of (i) C? -C? 2-alkyl, (ii) C2-Ci2-alkenyl, (? Ii) cycloalkyl, (iv) (cycloalkyl) alkyl, (v) (cycloalkyl) alkenyl, (vi) cycloalkenyl, (vii) (cycloalkenyl) alkyl, (viii) (cycloalkenyl) alkenyl, (ix) aryl, (x) (aryl) alkyl, (xi) (aryl) alkenyl, (xii) heterocyclic, (xiii) alkyl (heterocyclic) and (xiii) (xiv) alkenyl (heterocyclic); and R12 and R36 are independently selected from the group consisting of (i) hydrogen, (ii) C? -C, 2-alkyl, (iii) C2-C? 2-alkenyl, (iv) cycloalkyl, (v) ) (cycloalkyl) alkyl, (vi) (cycloalkyl) alkenyl, (vii) cycloalkenyl, (viii) (cycloalkenyl) alkyl, (ix) (cycloalkenyl) alkenyl, (x) aryl, (xi) (aryl) alkyl, (xii) ) (aryl) alkenyl, (xiii) heterocyclic, (xiv) alkyl (heterocyclic) and (xv) alkenyl (heterocyclic); X is selected from the group consisting of (a) -C (= 0) -N (R ') -, (b) -N (R *) - C (= 0) -, (c) -C (= S) -N (R, (d) -N (R ') - C (= S) -, (e) -N (R') - S02-, and M -S? 2-N (R ") -, where R 'is hydrogen, C? -C3-lower alkyl or cyclopropyl; R2 is selected from the group consisting of (a) hydrogen, (b) C? -C6-alkyl, (C) (d) C3-C6-cycloalkyl, ( e) C5-C6-cycloalkenyl, (f) halo-C? -C6-alkyl and (g) halo-C? -C? alkenyl; or R2-X is where Y 'is -CH2-, -O-, -S- or -NH- and Y2 is -C (= 0) - or -C (Raa) (Rb), where Raa and Rbb are selected, independently from each other, from the group consisting of hydrogen, C, -C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, thiolmethyl, 1-thiolethyl, 2-thiolethyl, methoxymethyl, N-methylaminomethyl and methylthiomethyl; R3 and R4 are selected independently from each other, from the group consisting of (a) hydrogen, (b) cycloalkyl, (c) cycloalkenyl, (d) heterocyclic, (e) aryl, and (f) -Z-R14 where Z is (i) -C (R37a) (R37b ) -, (¡i) -C (R47) = C (R48) -, (iii) -C = C-, (iv) -C (= 0) - (v) -C (= S) -, ( vi) -C (= NR15) -, (vii) -C (R37a) (OR37c) -, (viii) -C (R37a) (SR37c) -, (ix) -C (R37a) (N (R37b) (R37c)) -, (x) -C (R37a) (R37b) -0-, (xi) -C (R37a) (R37b) -N (R37c) -, (xii) -C (R37a) (R37b) -N (0) (R37c), (xiii) -C (R37a) (R37b) -N (OH) -, (xiv) -C (R37a) (R37b) -S-, (xv) -C (R37a) (R37b) -S (?) -, (xvi) -C (R37a) (R37) -S (?) 2-, (xvii) -C (R37a) (R37b) -C (= 0) -, (xviii ) -C (R37a) (R37b) -C (= S) -, (ix) -C (R37a) (R37b) -C (= NR15) -, (xx) -C (R37a) (? R37c) -C (= 0) -, (xxi) -C (R37a) (SR37b) -C (=?) -, (xxii) -C (R37a) (OR37o) -C (= S) -, (xxiii) -C ( R37a) (SR37c) -C (= S) -, (xxiv) -C (= 0) -C (R37a) (OR37c) -, (xxv) -C (= 0) -C (R37a) (SR37c) - , (xxvi) -C (= S) -C (R37a) (OR37c) -, (xxvii) -C (= S) - C (R37a) (SR37c) -, (xxviii) -C (R37a) (OR37c) - C (R37a) (? R370) -, (xxix) -C (R37a) (SR37c) - C (R37a) (0R37 ° ) -, (xxx) -C (R37a) (0R37c) -C (R37a) (SR37c) -, (xxxi) -C (R37a) (SR37c) -C (R37a) (SR37c) -, (xxxii) -C (= 0) -C (= 0) -, (xxxiii) -C (= S) -C (= S) -, (xxxiv) -C (= 0) -? -, (xxxv) -C (=? ) -S-, (xxxvi) -C (= S) -0-, (xxxvii) -C (= S) -S-, (xxxviii) -C (= 0) -N (R37a) - (xxxíx) - C (= S) -N (R37a) -, (xl) -C (R37a) (R37b) -C (= 0) -N (R37") -, (xli) -C (R37a) (R37b) -C (= S) -N (R37a) -, (xlii) -C (R37a) (R37b) -C (= 0) -0-, (xliii) -C (R37a) (R37) -C (= 0) - S-, (xliv) -C (R37a) (R37b) -C (= S) -0-, (xlv) -C (R37a) (R37b) -C (= S) -S-, (xlvi) -C (R37a) (R37b) -N (R37b) -C (= 0) -, (xlvii) -C (R37a) (R37) -N (R37) -C (= S) -, (xlviii) -C (R3 a) (R37b) -0-C (= 0) -, (xlix) -C (R37a) (R3b) -SC (= 0) -, (I) -C (R37a) (R37b) -0-C (= S) -, (li) -C (R37a) (R37b) -SC (= S) -, (Mi) C (R37a) (R37b) -N (R37b) -C (= 0) -N (R37a ) -, (liii) -C (R37a) (R37b) -N (R37b) -C (= S) -N (R37a) -, (liv) -C (R37a) (R37b) -N (R37) -C (=?) - 0-, (Iv) C (R37a) (R37b) -N (R37b) -C (= 0) -S-, (Ivi) -C (R37a) (R37b) -N (R37b) - C (= S) -0-, (Ivii) -C (R37a) (R37b) -N ( R37b) -C (= S) -S-, (Iviii) -C (R37a) (R37b) -0-C (=?) - N (R37") -, (lix) -C (R37a) (R3b ) -SC (= 0) -N (R37a) -, (Ix) -C (R37a) (R37b) -? - C (= S) -N (R37a) -, (Ixi) -C (R37a) (R37b) ) -SC (= S) -N (R37a) -, (Ixíi) C (R37a) (R37b) -0-C (= 0) -0-, (Ixiii) -C (R37a) (R37b) -SC ( = 0) -0-, (Ixív) -C (R37a) (R37b) -0-C (= 0) -S-, (Ixv) -C (R37a) (R37b) -SC (=?) - S- , (Ixvi) -C (R37a) (R37b) -0-C (= S) -0-, (Ixvii) -C (R37a) (R37) -SC (= S) -0-, (Ixviii) -C (R37a) (R37b) -0-C (= S) -S-, (Ixix) -C (R37a) (R37b) -SC (= S) -S- or (Ixx) -C (R37a) (R37b) -C (R37a) (? R37c) -; R, 4 is (i) hydrogen, (ii) C? -Ci2-alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) thiol-substituted alkyl, (vi) alkyl R37c-0- substituted, (v) alkyl R37c-S-substituted, (vm) aminoalkyl, (ix) alkyl (R37o) N H-substituted, (x) alkyl (R37a) (R37c) N-substituted, (xi) alkyl R37aO- ( 0 =) C-substituted, (xii) alkyl R37a-S- (0 =) C-substituted, (xiii) alkyl R37aO- (S =) C-substituted, (xiv) alkyl R37a-S- (S =) C -substituted, (xv) alkyl (R37aO) 2-P (=?) - substituted, (xvi) cyanoalkyl, (xvi) C2-Ci2-alkenyl, (xviii) haloalkenyl, (xix) C2-Ci2-alkynyl, (xx) ) cycloalkyl, (xxi) (cycloalkyl) alkyl, (xxii) (cycloalkyl) alkenyl, (xxiii) (cycloalkyl) alkynyl, (xxiv) cycloalkenyl, (xxv) (cycloalkenyl) alkyl, (xxvi) (cycloalkenyl) alkenyl, (xxvii) (cycloalkenyl) alkynyl, (xxviii) aryl, (xxix) (aryl) alkyl, (xxx) (aryl) alkenyl, (xxxi) (aryl) alkynyl, (xxxii) heterocyclic, (xxxiii) alkyl (heterocyclic), (xxxiv) alkenyl (heterocyclic) or (xxxv) (heterocyclic) alkynyl, with the proviso that R14 is other than hydrogen when Z is -C (R37a) (R37b) -N (R37) -C (=?) - 0-, -C (R37a) (R37b) -N (R37b) -C (= S) -? -, C (R37a) (R37b) -N (R37b) -C (= 0) -0-, -C (R37a) (R37b) -N (R37b) -C (= S) - S-, C (R37a) (R37) -0-C (= 0) -0-, -C (R37a) (R37b) -? - C (= S) -0-, -C (R37a) (R37" ) -SC (= 0) -0-, -C (R37a) (R37b) -SC (= S) -? -, -C (R37a) (R37b) -0-C (= 0) -S-, - C (R37a) (R37b) -0-C (= S) -S-, -C (R37a) (R37b) -SC (= 0) -S or -C (R37a) R37b) -SC (= S) - S-; R 37a R 7b R47 and R ß are added at each occurrence, independently of each other, of the group consisting of (i) hydrogen, (ii) C? -Ci2-alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) al coxyalkyl, (vi) C2-Ci2-alkenyl, (vii) haloalkenyl, (viii) C2-Ci2-alkyne, (ix) cycloalkyl, (x) (c? cloalqu? l) alkyl, (xi) (c? cloalqu? l) alken? lo, (xn) (c? chloralkyl) alkyl, (xiu) cycloalkenyl, (xiv) (c? alkoalken?) alkyl, (xv) (c? alkoalken?) alkenyl, (xvi) ( c? cloalquen? l) alternating it, (xvn) aplo, (xvni) (apl) allo, (xix) (ar? l) alken? lo, (xx) (apl) al? n? , (xxi) heterocyclic, (xxn) alkyl (heterocyclic), (xxm) alkenyl (heterocyclic) and (xxiv) alkylene (heterocyclic), R37c is selected group formed by (i) hydrogen, (n) C? -C12-alkyl, (ni) haloalkyl, (iv) C2-C12-alkenyl, (v) haloalkenyl, (vi) C2-C12-alkenyl, ( vn) cycloalkyl, (vi n) (c? cloalqu? l) alkyl, (ix) (c? chloralqu? l) alken? lo, (x) (c? cloalqu? l) alkyne, (xi) cycloalkenyl, (xn) (c? alkoalken?) alkyl, (XIII) (c? alkoalken?) alkenyl, (xiv) ( c? cloalquen? l) alternating it, (xv) aplo, (xvi) (ar? l) allo, (xvn) (apl) alken? lo, (xvni) (apl) al? n? , (xix) heteroocich, (xx) alkyl (heterocyclic), (xxi) alkenyl (heterocyclic), (xxii) alkylene (heterocyclic), (xxin) - C (=?) - R14, (xxiv) -C (= S) -R, (xxv) -S (0) 2 -R14 and (xxvi) hydroxyalkyl, or when Z is -C (R37a) (R37b) - N (R37c) -, then when N (R37c) and R14 are taken together they constitute an azide group, or when Z is -C (R37a) (R37b) -N (0) (R37c) -, then when N (0) (R37c) and R14 are taken together to constitute an N-oxidized 3-7 membered heterocyclic ring possessing at least one nitrogen atom in the N-oxidized ring, or when Z is -C (R37a) ( OR3 c) -, -C (R37a) (SR37c) - or -C (R37a) (N (R37b) (R37c)) -, then R37a, R14 and the carbon atoms at which are joined when taken together form a cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl ring; R15 is selected from the group consisting of (i) hydrogen, (ii) hydroxy, (iii) amino, (v) C? -C? -alkyl, (v) haloalkyl, (vi) C2-C2-alkenyl, (vii) haloalkenyl, (viii) cycloalkyl, (ix) (cycloalkyl) alkyl, (x) (cycloalkyl) alkenyl, (xi) cycloalkenyl, ( xii) (cycloalkenyl) alkyl, (xiii) (cycloalkenyl) alkenyl, (xiv) aryl, (xv) (aryl) alkyl, (xvi) (aryl) alkenyl, (xvii) heterocyclic, (xviii) alkyl (heterocyclic) and (xix) alkenyl (heterocyclic), or R3 and R4 taken together, with the atom to which they are attached, form a carbocyclic or heterocyclic ring having 3 to 8 ring atoms, Rs is selected from the group consisting of (a) hydrogen, (b) -CH (R3S) 2 , (c) -O-R40, (d) Cz-C-alkynyl, (e) cyclopropyl, cyclobutyl, (g) -C (= Q1) -R17 and (h) -N (R19) 2 where Q1 is O , S or N (R18); R17 and R18 are independently selected, at each occurrence, from the group consisting of hydrogen, methyl and ethyl; R19, R38 and R40 are independently selected, at each occurrence, from the group consisting of (i) hydrogen, (ii) C? -C1 -alkyl, (iii) haloalkyl, (iv) C2-C12-alkenyl, (v) haloalkenyl (vi) cycloalkyl, (vii) (cycloalkyl) alkyl, (viii) (cycloalkyl) alkenyl, (ix) cycloalkenyl, (x) (cycloalkenyl) alkyl, (xi) (cycloalkenyl) alkenyl, (xii) aryl, (xiii) (aryl) alkyl, (xiv) (apl) alkenyl, (xv) heterocyclic, (XVI) alkyl (heterocyclic) and (xv) alkenyl (heterocyclic); Y is selected from the group consisting of (a) hydrogen, (b) d-Cs-alkyl, (c) C? -C -haloalkyl, (d) C2-C3-alkenyl, (e) C2-C5-haloalkenyl, ( f) C2-C5-alkynyl, (g) C3-C5-cycloalkyl, (h) C3-C5-cycloalkyl-C? -a-C3-alkyl, (i) C5-cycloalkenyl, (j) C3-cycloalkenyl-C ? -a-C3-alkyl, (k) C5-cycloalkenyl-C2-a-C3-alkenyl, (I) - (CHR39) "OR20, (m) -CH (OR20) -CH2 (OR20), (n) - (CHR39) "SR21, (o) - (CHR39)" CN, (p) - (CHR39) N3, (q) phenyl, (r) halo-substituted phenyl, (s) - (CH R39) "C ( = Q2) R22, (t) - (CHR39) "N (= Q3), (u) -N (0) = CHCH3, (v) - (CHR39) nNR23R24, (w) halo and (x) a heterocyclic ring which has 3 to 6 atoms in the ring; where the value of n is 0, 1 or 2; Q2 is O, S, NR25 or CH R26; and Q3 is NR41 or CHR42; in each occurrence R20 is independently (i) hydrogen, (i) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) C? -C3-haloalkyl, (vii) vinyl, (viii) propenyl, (vi) x) isopropenyl, (x) allyl, (xi) C2-C3-haloalkenyl, (xii) amino, (xiii) -N HCH3, (xiv) -N (CH3) 2, (xv) -N HCH2CH3, (xvi) -N (CH3) (CH2CH3), (xvii) -N (CH2CH3) 2 or (xviii) -N (= CH2); R21 is (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) C? -C3-haloalkyl, (vii) vinyl, (viii) propenyl, (vi) ix) isopropenyl, (x) allyl or (xi) C2-C3-haloalkenyl; R22 is (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) hydroxy, (vn) thiol, (vin) ethoxy, (ix) ethoxy, (x) n-propoxy, (xi) isopropoxy, (xn) cyclopropyloxy, (xin) methylthio, (xiv) ethylthio, (xv) n-propylthio, (xvi) isopropylthio, (xvii) cyclopropylthio, (XVIII) vinyl, (xix) propenyl, (xx) isopropenyl, (xxi) halo, (xxu) -N (R28a) (R28b), (xxm) - CH2R29, (xxiv) aminomethyl, (xxv) hydroxymethyl, (xxvi) thiolmethyl, (XXVII) -NHN H2, (XXVIII) -N (CH3) N H2 or (xxix) -NH NH (CH3), R23 and R39 are, independently of one another, hydrogen or methyl, R4 and R42 are, independently of each other, hydrogen, methyl or ethyl, R24 is selected from the group consisting of (1) hydrogen, (11) C, -C4-alkyl, (111) C2-C4-alkenyl, (iv) C2-C4-alkyl, (v) cyclopropyl, (vi) -C (= Q ") - R30, (v) -OR31 and (vi) -N (R3) 2, where Q4 is O, S or N (R33), R25 is hydrogen, hydroxy, methyl, ethyl, amino, -CN or -N02, The group R26 is hydrogen, methyl or ethyl, R28a is hydrogen, hydroxy, methyl, ethyl, amino, -N HCH3, -N (CH3) 2, methoxy, ethoxy or -CN, R28b is hydrogen, methyl or ethyl, or else, R 2a, R 28b and the nitrogen to which they are attached, taken together represent azetidinyl, the group R 29 is hydrogen, hydroxy, thiol, methyl, ethyl, amino, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino, the group R 30 is hydrogen, methyl, ethyl, -OR34, -SR34, -N (R35) 2, -NHOH, -NHNH2, -N (CH3) NH2 or -N (CH2CH3) NH2, substituents R31 and R32 in each occurrence, they are, independently of one another, hydrogen, methyl or ethyl; the group R33 is hydrogen, hydroxy, methyl, ethyl, amino, -CN or -N02; the group R34 is methyl or ethyl; the group R 35 is, independently, hydrogen, methyl or ethyl; with the proviso that when Q2 is CH R26 then R22 is selected from the group consisting of hydrogen, -CH3, -C2H5, -C3H7, -0CH3, -SCH3, -O-C2H5 and -S-C2H5, and with the proviso that when R3 and R4 are each hydrogen, then Y is different from hydrogen; R6 and R7 are independently selected from the group consisting of (a) hydrogen, (b) C? -C? -alqu? lo, (c) C2-C12-alkenyl, (d) cycloalkyl, (e) (cycloalkyl) alkyl, (f) (cycloalkyl) alkenyl, (g) cycloalkenyl, (h) (cycloalkenyl) alkyl, (i) ) (cycloalkenyl) alkenyl, (j) aryl, (k) (aryl) alkyl, (I) (aryl) alkenyl, (m) heterocyclic, (n) alkyl (heterocyclic) and (o) alkenyl (heterocyclic); and R8, R9 and R10 are independently selected from the group consisting of (a) hydrogen, (b) C, -C6-alkyl, (C) C2-C6-alkenyl, (d) C3-C6-cycloalkyl, (e) C3-C6-cycloalkenyl, and (f) fluorine, with the proviso that the total amount of atoms, other than hydrogen, in each of R8, R9 and R10, is 6 atoms or less. Preferred compounds of the invention are compounds having the relative stereochemistry shown in Formula II: II or a salt, an ester or a prodrug acceptable for pharmaceutical use thereof, wherein R1, R2R3, R4, R5, R6, R7, R8, R9, R10, X and Y are as defined above and where R3 and R4 are not the same. Other preferred compounds of the invention are compounds possessing the relative stereochemistry shown in Formula III: III or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein R1, R2R3, R4, R5, R6, R7, R8, R9, R10, X and Y are as defined above and where R3 and R4 are not the same. Other preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is as defined above; -X-R2 is R2-C (= 0) -N H-, R2-N HC (= 0) -, R2-N H-S02- or R2-S02-N H-, where R2 is C? -C3 -lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C2-C3-alkenyl or -X-R2 is where Y1 is -CH2-, -O-, -S- or -N H- and Y2 is -C (= 0) - or -C (Raa) (Rb °) -, where Raa and Rbb are selected, independently from yes, from the group consisting of hydrogen, C? -C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, thiolmethyl, 1-thiolethyl, 2-thiolethyl, methoxymethyl, N-? methylaminomethyl and methylthiomethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, wherein Z and R14 are as defined above and wherein one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl: R6 and R7 are, independently of each other, hydrogen or lower alkyl; R8 and R9 are, independently of each other, hydrogen, fluorine or lower alkyl; ? 3í ?, ... jx.

R is hydrogen, fluorine or lower alkyl; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (0) = CHCH3, -NR 3R24 or a heterocyclic ring it has 3 to 6 atoms in the ring, where R22, R23, R24, Q2 and Q3 are as defined above. The most preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is as defined above: -X-R2 is R2-C (= 0) - NH-, R2-NH-C (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C? -C3-lower alkyl, halo C? -C3-lower alkyl, C2 -C3-alkenyl or C2-C3-alkenyl halo or -X-R2 is where Y1 is -CH2- and Y2 is -C (=?) - or -C (Raa) (Rbb), where Raa and R b are independently selected from the group consisting of hydrogen, C? -C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, wherein Z and R14 are as defined above and wherein one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl, R6 and R7 are, independently of each other, hydrogen or lower alkyl; R8 and R9 are, independently of each other, hydrogen or lower alkyl; R10 is hydrogen or lower alkyl, and Y is C2-C5-alkenyl, C2-C5-haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (0) = CHCH3 or a heterocyclic ring possessing 5 atoms in the ring and which also contains one or two double bonds, where R22, Q2 and Q3 are as defined above. Even more preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R is as defined above; -X-R2 is R2-C (= 0) -N H-, R -N HC (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C? -C3- lower alkyl, halo C, -C3-lower alkyl, C2-C3-alkenyl or halo C? -C3-alkenyl or -X-R2 is where Y1 is -CH2- and Y2 is -C (=?) - or -C (Raa) (R b), where Raa and Rbb are independently selected from the group consisting of hydrogen, C? -C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, wherein Z and R14 are as defined above and wherein one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl; R6 and R7 are, independently of each other, hydrogen or lower alkyl; Ra and R9 are, independently of each other, hydrogen or lower alkyl; R10 is hydrogen or lower alkyl; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring with 5 ring atoms and also containing one or two double bonds. Still more preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof wherein R is -C02H-, -X-R2 is R2-C (=?) - N H-, R2-N HC (= 0) -, R2-NH-S02- or R -S02-N H-, where R2 is C, -C3-lower alkyl or halo-C? -C3-lower alkyl, R3 and R 4 are selected, independently from each other, from hydrogen, heterocyclic and -Z-R 14, wherein Z and R 14 are as defined above and wherein one of R 3 and R 4 is other than hydrogen; R5 is hydrogen or lower alkyl; R6 and R7 are independently hydrogen or lower alkyl; R8 and R9 are independently hydrogen or lower alkyl; R 0 is hydrogen or lower alkyl; and Y is C2-C5-alkenyl, C? -Cs-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. The still more preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is -C? 2H; -X-R2 is R2-C (= 0) -N H-, R2-N HC (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C? -C3- lower alkyl or halo-C? -C3-lower alkyl; R 4 is hydrogen or lower alkyl and R 3 is heterocyclic or -Z-R 14, wherein Z and R 4 are as defined above; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R 0 is hydrogen; and Y is C2-C-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Still other more preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is -C? 2H; -X-R2 is R2-C (= 0) -N H-, R -N HC (= 0) -, R2-N H-S02- or R2-S? 2- N H-, where R2 is C? -C3-lower alkyl or halo C? -C3-lower alkyl; R 4 is hydrogen or lower alkyl and R 3 is (a) heterocyclic, (b) alkyl, (b) cycloalkyl, (d) cycloalkylalkyl, (e) alkenyl, (f) alkynyl, (g) -C (= 0) -R14, (h) -C (R37a) (OR37c) -R14 or (i) -C (R37a) (R37 °) -N (0) (R37o) R14, where R 4 is (i) alkyl, (ii) cycloalkyl, (ni) cycloalkylalkyl, (iv) alkenyl, (v) haloalkyl, (vi) haloalkenyl, (vii) aryl, (viii) arylalkyl, (ix) heterocyclic, (vi) x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xii) alkoxyalkyl, (xiii) cyanoalkyl, (xiv) alkyl (R37aO) - (0 =) C-substituted or (xv) alkyl (R37aO) 2-P (= 0) -replaced; 37a and R 37b are independently isolated from each other, from the group consisting of (i) hydrogen, (ii) lower alkyl and (iii) lower alkenyl; Y hydrogen, (ii) lower alkyl or (iii) lower alkenyl; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R10 is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Still more preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is -C02H; -X-R2 is R2-C (=?) - N H-, R -NH-C (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C? -C3 lower alkyl or halo C, -C3-lower alkyl; R4 is hydrogen and R3 is (a) heterocyclic, (b) alkyl or (c) - C (R3Ta) (OR37o) -R14, where R14 is (i) alkyl, (h) cycloalkyl, (iii) cycloalkylalkyl, (iv) alkenyl, (v) haloalkyl, (vi) haloalkenyl, (vii) aryl, (viii) arylalkyl, (ix) heterocyclic, (x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xii) alkoxyalkyl, (xiii) cyanoalkyl, (xiv) alkyl (R37aO) - (0 =) C-substituted or (xv) alkyl (R37a?) 2-P (=?) - substituted; 37a and R37b are independently separated from each other, from the group consisting of (i) hydrogen, (ii) lower alkyl and (iii) lower alkenyl; and R37c is (i) hydrogen, (ii) C? -C3-lower alkyl or (iii) allyl; R5 is hydrogen; R8 and R7 are hydrogen; Rs and R9 are hydrogen R10 is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Other highly preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R is -C? 2H, -X-R2 is R2-C (=?) - NH- or R2-S02-NH-, where R2 is d-C3-lower alkyl or halo C? -C3-lower alkyl; R4 is hydrogen and R3 is (a) heterocyclic, (b) alkyl or (c) -C (R37a) (OR37c) -R 14 where R14 is (i) lower alkyl, (ii) lower alkenyl, (iii) hydroxy-substituted lower alkyl or (iv) alkoxy-substituted lower alkyl; R37a is (i) hydrogen, (ii) lower alkyl or (iii) lower alkenyl; and R370 is (i) hydrogen, (ii) C? -C3-lower alkyl or (iii) allyl; Rs is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R 0 is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Other highly preferred compounds of the invention are compounds of Formula I or II or III or a salt, an ester or a prodrug thereof, wherein R1 is -C02H; -X-R2 is R2-C (= 0) -N H- or R2-S? 2-NH-, where R2 is C, -C3-lower alkyl or halo C? -C3-lower alkyl: R4 is hydrogen and R3 is -C (R37a) (OR37c) -R14, where R14 is lower alkyl or lower alkenyl; R37a is lower alkyl or lower alkenyl; and R37c is hydrogen, C? -C3-lower alkyl or allyl; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Preferred R1 substituents include -C02H or esters or prodrugs thereof. Preferred esters include C2-C6-lower alkyl esters or substituted or unsubstituted benzyl esters. Preferred R1 substituents also include -S (0) 2N HC (= 0) R1 1, where R1 is as defined above. More preferred substituents R1 include -C02H or esters or prodrugs thereof. More preferred esters include C2-C6-lower alkyl esters or substituted or unsubstituted benzyl esters. Preferred substituents -X-R2 include R2-C (= 0) -N H-, R2-NH-C (= 0) -, R2-N H-S0 - or R -S02-N H-, where R2 is d-C3-lower alkyl, halo dd-lower alkyl, dd-alkenyl or halo C2-C3-alkenyl or -X-R2 is: where Y1 is -CH2-, -O-, -S- or -N H- and Y2 is -C (= 0) - or -C (Raa) (Rbb) -, where R "and Rbb are selected, independently from yes, from the group consisting of hydrogen, dd-lower alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, thiolmethyl, 1-thiolethyl, 2-thiolethyl, methoxymethyl, N-methylaminomethyl and methylthiomethyl. More preferred substituents -X-R2 include R2-C (= 0) -N H-, R2-N HC (= 0) -, R -N H-S02- or R2-S02-N H-, where R2 is d-C3-lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C2-C3-alkenyl or -X-R2 is where Y1 is -CH2- and Y2 is -C (=?) - or -C (Raa) (Rbb) -, where Raa and Rbb are independently selected from the group consisting of hydrogen, C? -C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl. Even more preferred substituents -X-R2 include R -C (= 0) -N H-, R2-N HC (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C, -C3-lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C2-C3-alkenyl. Even more preferred substituents -X-R2 include R2-C (= 0) -N H-, R -NH-C (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is C, -C3-lower alkyl or halo-C? -C3-lower alkyl. The most preferred substituents -X-R2 still include R2-C (= 0) -N H-, R2-N HC (= 0) -, R2-N H-S02- or R2-S02-NH-, where R2 is d-C2-lower alkyl or halo Ci-d-lower alkyl and, especially, CH3- C (= 0) -N H-, CF3-C (= 0) -N H-, CH3-SO2-NH-0 CF3-S? 2-NH-. Preferred substituents R3 and R4 are selected, independently from each other, from the group consisting of hydrogen, heterocyclic and -Z-R14 where Z and R14 are defined with the broader description detailed hereinabove and where one of R3 and R4 is different of hydrogen. More preferably, the substituent R4 is hydrogen or lower alkyl and R3 includes heterocyclic or -Z-R14, where Z and R4 are defined with the broader description detailed hereinabove. Even more preferably, the substituent R4 is hydrogen or lower alkyl and R3 includes (a) heterocyclic, (b) alkyl, (c) cycloalkyl, (d) cycloalkylalkyl, (e) alkenyl, (f) alkynyl, (g) - C (=?) - R14, (h) -C (R37a) (OR37c) -R14 or (i) -C (R37a) (R37) -N (0) (R37c) R14, where R14 is (i) alkyl, (ii) cycloalkyl, (iii) cycloalkylalkium, (iv) alkenyl, (v) haloalkyl, (vi) haloalkenyl, (vii) aryl, (viii) arylalkyl, (ix) heterocyclic, (x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xii) alkoxyalkyl, (xiii) cyanoalkyl, (xiv) alkyl (R37?) - (0 =) C-substituted or (xv) alkyl (R37aO) 2-P (=?) - substituted; R37a and R37_ are separated, independently from each other, from the group consisting of (i) hydrogen, (ii) lower alkyl and (iii) lower alkenyl; and R37c is (i) hydrogen, (ii) lower alkyl or (iii) lower alkenyl. Even more preferably, the R4 substituent is hydrogen and R3 includes (a) heterocyclic, (b) alkyl or (c) -C (R37a) (OR37o) -R14 where R14 is (i) alkyl, (n) cycloalkyl, (ni) cycloalkylalkyl, (iv) alkenyl, (v) haloalkyl, (vi) haloalkenyl, (vn) aplo,. { vi u) aplakyl, (ix) heterocyclic, (x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xu) alkoxyalkyl, (XIII) cyanoalkyl, (xiv) alkyl (R37aO) - (0 = ) C-substituted or (xv) alkyl (R37aO) 2-P (= 0) -sust? Tu? Do, R37a and R37b g group consisting of (i) hydrogen, (n) lower alkyl and (ni) lower alkenyl, Y R37c is (i) hydrogen, (n) C? -C3 lower alkyl or (ui) alkyl In addition, most preferably, the substituent R4 is hydrogen and R3 includes (a) heterocyclic, (b) alkyl or (c) -C (R37a) (OR37,:) - R14 where R14 is (i) lower alkyl, (II) lower alkenyl, (ni) hydroxy-substituted lower alkyl or (iv) lower alkoxy-substituted alkyl, R37a is (i) hydrogen, (n) lower alkyl or (ni) lower alkenyl, and R37c is (i) hydrogen, (n) C? -C3 lower alkyl or (MI) aillo In addition, more preferably, the substitute R 4 is gen and R 3 includes lower C or lower alkenyl, is hydrogen, d-d-lower alkyl, and, especially, where R37c is hydrogen or methyl. Preferred R5 substituents include hydrogen or lower alkyl. More preferably, R5 is hydrogen. Preferred substituents R6 and R7 include, independently of each other, hydrogen and lower alkyl. More preferably, R6 and R7 are hydrogen. Preferred substituents R8, R9 and R10 include, independently of one another, hydrogen, fluorine and lower alkyl. More preferably, R8, R9 and R10 are hydrogen. The preferred Y substituent includes d-Cs-alkenyl, C2-C5-haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (0) = CHCH3, -NR23R24 or a heterocyclic ring possessing to 6 atoms in the ring, where The most preferred substituent Y includes d-Cs-alkenyl, C2-C5 haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (0) = CHCH3 or a heterocyclic ring having 5 ring atoms and which also contains one or two double bonds, where R22, Q2 and Q3 are as defined above. The even more preferred substituent Y includes d-Cs-alkenyl, d-Cs-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. Representative alkenyl and haloalkenyl Y substituents include: -CH = CH2, -CH = CHF, -CH = CH-CH3, -CH = CH-CF3, -CH = CHCl, -CH = CHBr, -CH = CF2, -CH = CF (CH3), -CH = CF (CF3), -CH = CFCI, -CH = CFBr, -CH = C (CH3) 2, -CH = C ( CH3) (CF3), -CH = CCI (CH3), -CH = CBr (CH3), -CH = C (CF3) 2, -CH = CCI (CF3), -CH = CBr (CF3), -CH = CCI2, -CH = CCIBr, -CF = CH2, -CF = CHF, -CF = CH-CH3, -CF = CH-CF3, -CF = CHCI, -CF = CHBr, -CF = CF2, - CF = CF (CH3), -CF = CF (CF3), -CF = CFCI, -CF = CFBr, -CF = C (CH3), -CF = C (CH3) (CF3), -CF = CCI (CH3) ), -CF = CBr (CH3), -CF = C (CF3) 2, -CF = CCI (CF3), -CF = CBr (CF3), -CF = CCI2, -CF = CCIBr, -C (CH3) = CH2, -C (CH3) = CHF, -C (CH3) = CH-CH3, -C (CH3) = CH-CF3, -C (CH3) = CHCl, -C (CH3) = CHBr, -C ( CH3) = CF2, - (CH3) = CF (CH3), -C (CH3) = CF (CF3), -C (CH3) = CFCI, -C (CH3) = CFBr, -C (CH3) = C ( CH3) 2, -C (CH3) = C (CH3) (CF3), -C (CH3) = CCI (CH3), -C (CH3) = CBr (CH3), -C (CH3) = C (CF3) 2, -C (CH3) = CCI (CF3), -C (CH3) = CBr (CF3), -C (CH3) = CCI2, -C (CH3) = CCIBr, -C (CF3) = CH2, -C (CF3) = CHF, -C (CF3) = CH-CH3, -C (CF3) = CH-CF3, -C (CF3) = CHCl, -C (CF3) = CHBr, -C (CF3) = CF2, -C (CF3) = CF (CH3), -C (CF3) = CF (CF3), -C (CF3) = CFCI, -C (CF3) = CFBr, -C (CF3) = C (CH3) 2, -C (CF3) = C (CH3) (CF3), -C (CF3) = CCI (CH3), -C (CF3) = CBr (CH3), -C (CF3) = C (CF3) 2, -C (CF3) = CCI (CF3), -C (CF3) = CBr (CF3), -C (CF3) = CCI2, -C (CF3) = CCIBr, -CCI = CH2, -CCI = CHF, -CCI = CH-CH3, -CCI = CH-CF3, -CCI = CHCI, -CCI = CHBr, -CCI = CF2, -CCI = CF (CH3), -CCI = CF ( CF3), -CCI = CFCI, -CCI = CFBr, -CCI = C (CH3) 2, -CCI = C (CH3) (CF3), -CCI = CCI (CH3), -CCI = CBr (CH3), - CCI = C (CF3) 2, -CCN CCI (CF3), -CCI = CBr (CF3), -CCI = CCI2, -CCI = CCIBr, -CH = CH-CH2CH3, -CH = CF-CH2CH3, -CF = CH-CH2CH3, -CF = CF-CH2CH3, -CH = C (CH3) (CH2CH3), -CF = C (CH3) (CH2CH3), -CH = CCI (CH2CH3), -CF = CCI (CH2CH3), - C (CH3) = CH-CH2CH3, -C (CH3) = CF-CH2CH3, -CCI = CH-CH2CH3, -CCI = CF-CH2CH3, -C (CH2CH3) = CH2, -C (CH2CH3) = CHF, - C (CH2CH3) = CF2, -C (CH2CH3) = CH-CH3, -C (CH2CH3) = CF-CH3, -C (CH2CH3) = CH-CI, -C (CH2CH3) = CFCI Representative Y substituents which are heterocyclic rings with 5 ring atoms and also containing one or two double bonds include furanyl, dihydrofuranyl, didehydrodioxolanyl, dithiolyl, imidazolyl, imidazolinyl , isothiazolyl, isothiazoyl, isoxazoyl, isoxazolinyl, oxadiazolyl, oxadiazoyl, oxathiazoyl, oxazoyl, oxazoyl, oxazolinyl, pyrazolyl, pyrazolinyl, pyrrolyl, dihydropyrrolyl, tetrazolyl, tetrazolinyl, thiadiazolyl, thiadiazolinyl, thiazolyl, thiazolinyl, tiendo, dihydrothienyl, tpazolyl, triazolinyl Substituents and more Preferred include cis-propenyl, trans-propenyl, isobutenyl, cis-2-chloro vinyl, vinyl, 2,2-difluorovinyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isoxazolyl. The most preferred substituents Y include cis-propenyl, cis-2-chloroquine, vinyl, imidazolyl, pyrazolyl, oxazole, isoxazolyl, thiazolyl, isoxazolyl The preferred compounds of the invention n include compounds selected from the group consisting of Acid (±) - (2R, 3S, 5R, rR) -2- (1 -acetam? do-2-et? l-2-hydrox?) but? l- 3 - (c? s-propen-1 -? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1 'R, 2'S) -2- ( 1 -acetamido-2-hydroxy-2-methyl) pent-l-3- (c? S-propen-1-yl) -p? Rrol? D? N-5-carboxyl? co, Acid (±) - (2 R, 3S, 5R, 1 'R, 2'S) -2- (1 -acetam? do-2-et? l-2-h? drox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy) pentyl-3- (cis-propen-1-yl) -pyrrolidin-5-carboxylic acid , trifluoroacetic salt; Acid (±) - (2R, 3R, 5R, 1'R, 2'R) -2- (1-acetamido-2,3-dihydroxy) prop il-3- (cis- pro pen- 1-il) -pyrrolidine-5-carboxylic; Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (cis-propen-1-yl) -pyrrolidin- 5-carboxylic acid; (-) - (2R, 3S, 5R, 1'S) -2- (1 -acetamido-2-ethyl) butyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylate, ammonium salt; Acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-2,3-dimethoxy) propyl-3- (bi-propen-1-yl) -pyrrolidin- 5-carboxylic; Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methoxy-2-vinyl) ethyl-3- (cis-propen-1-yl) -pyrrolidin- 5-carboxylic; (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2-ethyl) butyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid; Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-isopropyl-N-methylamin-N-oxide)) ethyl-3- (cis-propen-1) -yl) -pyrrolidine-5-carboxylic acid; Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-ethyl-N-methylamin-N-oxide)) ethyl-3- (cis-propen-1) -yl) -pyrrolidine-5-carboxylic acid; (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-methoxy) butyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid; (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-methoxy) pentyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid; Acid (±) - (2R, 3R, 5R, 1"R, 2" S) -2- (1-acetamido-2-hydroxy) butyl-3- (p-razo l-3-yl) -pi rrol idi n-5-ca rboxí ico; Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy) butyl-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R 2'R) -2 - (1-Acetamido-1- (3,6-d? H? D-2-Hp? Rano-2-? L)) prop? L-3- (c? S-propen-1-? L ) -p? rrol? d? n-5-carbox? l? co, Acid (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -2 -al? Lo) et? L-3- (c? S- propen-1-? l) -pyrrolidone-5-carboxylic acid, acid (±) - (2R, 3S, 5R, 1'R, 2'S, 3'S) -2- (1- acetamido-2-hydrox? -3-met? l) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -4-v? n? l) but? l-3- ( c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1- acetamido-2-hydrox-3-c? an) prop? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-1- (3,6-d? h? dro-2-Hp? rano-2 -? l)) met? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2 R, 3S, 5R, 1'R, 2'S) -2- (1 -acetam id o-2, 3-d imethoxy) prop? L-3- (c? S-propen- 1-?) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, rR, 2'S) -2- (1-acetamido-2-h? drox? met? l-2-h? drox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid ( ±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-ethoxy?) Pent? L-3- (c? S-propen-1-? L) - pyrrolidone-5-carboxylic acid, acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox? -3) -d? met?) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-ethoxy? -3-v? N? L) prop? L-3- (c? S-propen-1-? L ) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1"R, 2'S) -2- (1-acetamido-2-hydrox? -2- (propen-2-? L)) et? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co •was e Acid (±) - (2R 3S.5R 1 'R, 2'S) -2- (1-acetamido-2-hydrox?) Hex? L-3- (c? S-propen-1-? L ) -pyrrolidone-5-carboxylic acid, (±) - (2R 3S, 5R, 1 S) -2- (1-acetamido-3-met? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S ) -2- (1-acetamido-2-hydroxyl) but? L-3-v? N? Lp? Rrol? D? N-5-carbox? L? Co, Acid (±) - ( 2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox?) Pent? L-3-v? N? Lp? Rrol? D? N-5-carbox Acid, (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-2-hydrox? et? l-2-hydrox) ?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (+) - (2R, 3S, 5R, 1"R , 2'R) -2- (1-acetamido-2-hydrox?) But? L-3-v? N? Lp? Rrol? D? N-5-carbox? L? Co, Acid ( ±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-2-methox?) Pent? L-3- (c? S-propen-1? ) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1, R, 2'R) -2- (1-acetamido-2-h? drox?) pent? l-3-v? n? lp? rrol? d? n-5-carboxíl? co, Acido (±) - (2R, 3S, 5R, 1'R) -2- (1-acetam) ? do-2-h? drox?) et? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R , 3S, 5R, 1"S) -2- (1-acetamido-3-met? L) but? L-3- (c? S-2-cl) gold-v? n-1-? l) -p? rrohd? n-5-carboxyl? co, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetam? do-3- met?!) but?! - 3-p? razol-3-? l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, rS, 3'R) -2- (1-acetamido-3-hydrox?) Pent? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5- carboxylic acid, (±) - (2R, 3R, 5R 1 'S) -2- (1-Acetamido-3-met? l) but? l-3- (t? azol- • 4-i l) -pyrrol id-n-5-ca rboxí Meo; Acid (±) - (2R, 3R, 5R, 1'S) -1-t-butoxycarbonyl-2- (1-acetamido-3-ethyl) butyl-3- (thiazol-2-yl) -pyrrolidin-5- carboxylic; (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid; (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (2,2-difluoro-vin-1-yl) -pyrrolidine-5-carboxylic acid; (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3-pyrazol-3-yl) -pyrrolidine-5-carboxylic acid; (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (isoxazol-3-yl) -pyrrolidine-5-carboxylic acid; (+) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (isoxazol-5-yl) -pyrrolidine-5-carboxylic acid; (+) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid; (±) - (2R, 3R, 5R, 1, S) -2- (1-Acetamido-3-methyl) butyl-3- (imidazol-4-yl) -pyrrolidine-5-carboxylic acid; and (+) - (2S, 3R, 5R, rS) -2- (1-Acetamido-3-methyl) butyl-3-aminopyrrolidine-5-carboxylic acid; or a salt, an ester or a prodrug acceptable for pharmaceutical use thereof. The most preferred compounds of the invention include compounds selected from the group consisting of: Acid (±) - (2R, 3S, 5R, 1'R) -2- (1-acetamido-2-ethyl-2-hydroxy) butyl-3 - (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid; Acid (±) - (2R, 3S, 5R, 1'R 2'S) -2- (1-acetamido-2-hydrox? -2-met? L) pent? L-3- (c? S -propen-1-? l) -pyrrolidone-5-carboxylic acid, (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetam) ? do-2-et? l-2-h? drox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox?) Pent? L-3- (c? S-propen-1-? l) -? rrol? d? n-5-carboxyl? co, tpfluoroacetic salt, Acid (±) - (2R, 3R, 5R, 1, R, 2'R) -2- (1-acetamido-2,3-d? H? Drox?) Prop? L-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetam? do-2-h? drox? -4-v? n? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, (-) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-2-et? L) but? L-3- (c? S-propen-1-? L) -p? Rhodium-5-carboxylate, ammonium salt, Acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-2,3- d? methox?) prop? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -2-v? N? L) et? L-3- (c? S-propen-1-? L) -p? r? r? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-acetam? do-2-et? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetam) ? do-2- (N-? soprop? lN-met? lam? nN-ox? do)) et? l-3- (c? s-propen-1-? l) -p? rrol? d? n -5-carbox? L? Co, Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-et? LN-met? Lam? NN-ox? Do)) et? L- 3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carboxyl? Co, Acid (±) - (2R, 3S, 5R, 1'R, 2, S) -2- (1-acetamido-2-methox?) But? L-3- (c? S-propen-1-) (l) -pyrrolidone-5-carboxylic acid, (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-) methox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3R 5R, 1 'R, 2'S) -2- ( 1-acetamido-2-hydroxyl) but? L-3- (p? Razol-3-? L) -pyrrolidone-5-carboxylic acid, (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox?) But? L-3- (c? S-propen-1-? L) - pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-1- (3 , 6-d? H? Dro-2-Hp? Rano-2-? L)) prop? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5- carbox? l? co, Acid (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -2 -al? Lo) et? L-3- (c? S- propen-1-?) -pyrrolidone-5-carboxylic acid, (+) - (2R, 3S, 5R, 1'R, 2'S, 3'S) -2- (1-acetam? do-2-hydrox? -3-met? l) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -4-v? N? L) but? L-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetam? do-2-hydrox -3-c? an) prop? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid ( ±) - (2R, 3S, 5R, 1, R, 2'S) -2- (1-acetamido-1- (3,6-d? H? Dro-2-Hp? Rano-2-? L) ) met? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2,3-d? Methox?) Prop? L-3- (c? S-propen- 1-?) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1, R, 2'S) -2- (1-acetamido-2-) h? drox? met? l-2-hydrox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid ( ±) - (2R, 3S, 5R, 1"R, 2'S) -2- (1-acetamido-2-ethoxy?) Pent? L-3- (c? S-propen-1-? L) - pyrrolidone-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox? -3) -d? met? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-ethoxy-3-vinyl) propyl-3- (cis-propen-1-yl) -pyrrolidine -5-carboxylic acid; Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy-2- (propen-2-yl)) ethyl-3- (cis-propen -1-yl) -pyrrolidine-5-carboxylic acid; and Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy) hexyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid; or a salt, an ester or a prodrug acceptable for pharmaceutical use thereof. The term "acid protecting group", as used herein, refers to groups used to protect acid groups (eg, groups -C02H, -SO3H, -S? 2H, -P? 3H2, -P02H and similar) against unwanted reactions during the synthesis procedures. The commonly used acid protecting groups are described in T.H. Greene and P.G.M. Wuts, Protective Groups in Orqanic Svnthesis. 2nd edition, John Wiley & Sons, New York (1991). Very often, said acid protecting groups are esters. Said esters include: alkyl esters, especially lower alkyl esters, including, but not limited to, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentylesters; and similar ones; arylalkyl esters including, but not limited to, benzyl, phenethyl, 3-phenylpropyl, naphthylmethyl esters and the like, wherein the aryl part of the arylalkyl group is substituted or unsubstituted, as defined hereinbefore; silylesters, in particular, (tp-alkyl? nfepor) s? l? esters, (di-alkyl? nfepor) (apl) s? l? lesteres y (alkyl? nfer? or) (d? -ar? l) s ? leters, including, but not limited to, tpmethylsilyl, tethylsilyl, isopropyldimethylsilyl, t-butyl and methyl sityl, methyldiisopropylsihl, methyldi-t-butylsilyl, tisopropylsilyl, methyldifemlsilyl, isopropyldiphenylsilyl, butyldiphenylsihl, phenyldisopropylsilyl esters and the like, and the like. Preferred acids are lower alkyl esters The term "activated carboxylic acid group", as used herein, refers to acid halides, such as acid chlorides, and also refers to activated ester derivatives, including, but not limited to, , anhydrides derived from formic and acetic acid, anhydrides removed from alkoxycarbonyl halides, such as isobutyloxycarbonyl chloride and the like, anhydrides derived from the reaction of carboxylic acid with N, N'-carbon? ldum? dazol and similar, esters derived from N-hydroxysuccinimide, esters derived from N-hydroxyphthalimide, esters derived from N-hydroxybenzotpazole, esters derived from Nh? drox? -5-norbornen-2,3-d? carbox? m? da, esters derived from 2,4, 5-tpclorophenol, esters derived from p-nitrophenol, esters derived from phenol, esters derived from pentachlorophenol, esters derived from 8-hydroxyquinoline and the like The term "aciio", as used herein, refers to groups that have the formula -C (=?) - R95, where R95 is hydrogen or an alkyl group Preferred alkyl groups such as R are lower alkyl groups. Representative examples of acyl groups include groups such as, for example, formyl, acetyl, propionyl and the like. The term "acylamino", as used herein, refers to groups having the formula -N H R89, where R89 is an acyl group. Representative examples of acylamino include acetylamino, propionylamino and the like. The term "alkenyl", as used herein, refers to a straight or branched chain hydrocarbon radical containing from 2 to 15 carbon atoms and which also contains at least one carbon-carbon double bond. The term "lower alkenyl" refers to straight or branched chain alkenyl radicals, containing from 2 to 6 carbon atoms. Representative examples of alkenyl groups include groups such as, for example, vinyl, 2-propenyl, 2-methyl-1-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl and the like. The term "alkenylene", as used herein, refers to a divalent group derived from a straight or branched chain hydrocarbon containing from 2 to 15 carbon atoms and which also contains at least one carbon-double bond. carbon. The term "lower alkenylene" refers to a divalent group derived from a straight or branched chain alkene group having from 2 to 6 carbon atoms. Representative examples of alkenylene groups include groups such as, for example, CH = CH-, -CH2CH = CH-, -C (CH3) = CH-, -CH2CH = CHCH2-, and the like. The term "alkenyloxy", as used herein, refers to groups having the formula -OR81, wherein R81 is an alkenyl group. The term "alkoxy", as used herein, refers to groups having the formula -OR99, wherein R99 is an alkyl group. Preferred R99 groups are lower alkyl groups. Representative examples of alkoxy groups include groups such as, for example, methoxy, ethoxy, tert-butoxy, and the like. The term "alkoxyalkoxy", as used herein, refers to groups having the formula -0-R98-0-R97, where R97 is lower alkyl, defined hereinbefore, and R96 is a lower alkylene group . Representative examples of alkoxyalkoxy groups include groups such as, for example, methoxymethoxy, ethoxymethoxy, t-butoxymethoxy and the like. The term "alkoxyalkyl", as used herein, refers to an alkyl radical to which an alkoxy group is attached, for example, methoxymethyl, methoxylpropyl and the like. The term "alkoxycarbonyl", as used herein, refers to groups having the formula, -C (= 0) -R80, wherein R80 is an alkoxy group. The term "alkoxycarbonylalkyl", as used herein, refers to groups having the formula, -C (= 0) -R79, a linkage to the related molecular portion via an alkylene linkage, wherein R79 is a alkoxy group.

As used herein, the term "alkyl" refers to straight or branched chain hydrocarbon radicals containing from 1 to 12 carbon atoms. The term "lower alkyl" refers to straight or branched chain alkyl radicals containing 1 to 6 carbon atoms Representative examples of alkyl groups include groups such as, for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n- pentyl, 1 -methylbutyl, 2, 2-d? methyl butyl, 2-methylpentyl, 2, 2-d? met? l-propyl, n-hexyl and the like The hydrocarbon chains in the alkyl groups, or the alkyl portion of an alkyl-containing substituent, may be optionally interrupted by one or two heteroatoms or hetero groups, independently selected from the group consisting of oxygen, -N (R27) - and sulfur, where R27, at each occurrence, is independently hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl or aplakyl and where two of said heteroatoms or heterogroups are separated by at least one carbon atom The term "alkylamino", as used herein, refers to groups possessing the formula -NHR91, where R91 is an alkyl group. Preferred R91 groups are lower alkyl groups. Representative examples of alkylamino include methylamino, ethylamino and the like The term "alkylene", as used herein, refers to a divalent group derived from a straight or branched chain saturated hydrocarbon group having from 1 to 15 carbons. The term "lower alkylene" refers to a divalent group derived from a saturated linear or branched chain hydrocarbon group having from 1 to 6 carbon atoms. Representative examples of alkylene groups include groups such as, for example, methylene (-CH2-), 1,2-ethylene (-CH2CH2.) -1,1 -ethylene (-CH (CH3) -), 1, 3- propylene (-CH2CH2CH2-), 2,2-dimethylpropylene (-CH2C (CH3) 2CH2-) and the like. The hydrocarbon chains in the alkylene groups, or the alkylene portion of an alkylene-containing substituent, can optionally be interrupted by one or two heteroatoms or hetero groups independently selected from the group consisting of oxygen, -N (R27) - and sulfur, where R27, in each occurrence it is independently hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl or arylalkyl and where two of said heteroatoms or hetero groups are separated by at least one carbon atom. The term "alkylsulfonyl", as used herein, refers to the groups having the formula, -SO2-R78, where R78 is an alkyl group. Preferred R78 groups are lower alkyl groups. The term "alkylsulfonylamino", as used herein, refers to a group having the formula, -SO2-R77, attached to the related molecular portion by means of an amino bond (-NH-), where R77 is an alkyl group. Preferred R77 groups are lower alkyl groups. The term "alkynyl", as used herein, is refers to a straight or branched chain hydrocarbon radical containing from 2 to 15 carbon atoms and which also contains at least one carbon-carbon triple bond. The term "lower alkynyl" refers to straight or branched chain alkynyl radicals containing from 2 to 6 carbon atoms. Representative examples of alkynyl groups include groups such as, for example, acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, 1-butynyl and the like. The term "alkynylene", as used herein, refers to a divalent group derived from a straight or branched chain hydrocarbon containing from 2 to 15 carbon atoms and which also contains at least one carbon triple bond. carbon. The term "lower alkynylene" refers to a divalent group derived from a straight or branched chain alkynylene group of 2 to 6 carbon atoms. Representative examples of alkynylene groups include groups such as, for example, -C = C-, -CH2-CaC-, -C = C-CH2-, -CH (CH3) -CsC- and the like. The term "aminoalkyl", as used herein, refers to an alkyl radical to which an amino group (-N H2) is attached. The term "aryl", as used herein, refers to a carbocyclic ring system having 6-10 atoms in the ring and one or two aromatic rings. Representative examples of aryl groups include groups such as, for example, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl and Similar The aplo groups can be substituted or unsubstituted with one or two substituents, each independently selected from lower alkyl, halo, haloalkyl, haloalkoxy, hydroxy, oxo (= 0), hydroxyalkyl, alkenyloxy, alkoxy, alkoxyalkoxy, alkoxycarbonyl, alkoxycarbonylalkyl , thioalkoxy, amino, alkylamino, alkylsulfonyl, dialkylamino, acylamino, unsubstituted aryl, unsubstituted aplaxyl, unsubstituted aptalkoxy, unsubstituted artloxy, mercapto, cyano, nitro, carboxy, carboxaldehyde, N H2C (= 0) -, cycloalkyl, carboxyalkyl, alkylsulfonylamino, unsubstituted heterocycles, unsubstituted alkoxy (heterocyclic), unsubstituted alkoxy (heterocyclic), unsubstituted ox (heterocyclic) and -S03H The substituents Preferred are each and independently selected from the group consisting of lower alkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, alkenyloxy, alkoxy, alkoxyalkoxy, thioalkoxy, amino, alkylamino, dialkylamino, alkylsulfo nyl, acylamino, cyano and nitro Examples of substituted alloy include 3-chlorophenyl, 3-fluorophenol, 4-chlorophenol, 4-fluorophenol, 3,4-dichlorophenyl, 3-chloro-4-fluorophenyl. The term "(ar? l) alken? lo" refers to a lower alkenyl group having an aplo group attached thereto. Representative examples of groups (ar? l) alkenyl include groups such as, for example, femletilenyl, phenylpropenyl and the like The term "(aryl) alkyl" refers to a lower alkyl group. having an aplo group attached thereto. Representative examples of (aryl) alkyl groups include groups such as, for example, benzyl and phenylethyl. The term "arylalkoxy", as used herein, refers to a group having the formula, -O-R76, wherein R76 is an arylalkyl group. The term "(aryl) alkynyl" refers to an alkynylene group having an aryl group attached thereto. Representative examples of (aryl) alkynyl groups include groups such as, for example, phenylacetylenyl, phenylpropynyl and the like. The term "aryloxy," as used herein, refers to a group having the formula, -O-R72, wherein R72 is an aryl group. The term "carbamoyl", as used herein, refers to a group having the formula, -C (= 0) -N H2. The term "carboxyalkyl", as used herein, refers to a group having the formula, -R84-COOH, wherein R64 is a lower alkylene group. The term "cyanoalkyl," as used herein, refers to an alkyl radical to which a cyano group (-CN) is attached. The term "cycloalkenyl", as used herein, refers to an aliphatic ring system having 5 to 10 carbon atoms and 1 or 2 rings containing at least one double bond in the ring structure. The examples Representative of cycloalkenyl groups include groups such as, for example, cyclohexene, cyclopenten, norbornene and the like.

Cycloalkenyl groups can be substituted or unsubstituted with one, two or three substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, thioalkoxy, haloalkyl, mercapto, lower alkenyl and lower alkyl. Preferred substituents are independently selected from lower alkyl, lower alkenyl, haloalkyl, halo, hydroxy and alkoxy. The term "(cycloalkenyl) alkenyl", as used herein, refers to a cycloalkenyl group attached to a lower alkenyl radical. Representative examples of (cycloalkenyl) alkenyl groups include groups such as, for example, cyclohexenylethylene, cyclopentenethylene and the like. The term "(cycloalkenyl) alkyl," as used herein, refers to a cycloalkenyl group attached to a lower alkyl radical.Regional examples of (cycloalkenyl) alkyl groups include groups such as, for example, cyclohexenylmethyl, cyclopentenylmethyl , cyclohexylethylethyl, cyclopentenylethyl and the like The term "(cycloalkenyl) alkynyl", as used herein, refers to a cycloalkenyl group attached to a lower alkynyl radical.Regional examples of (cycloalkenyl) alkynyl groups include groups such as , for example, cyclohexenylacetylenyl, cyclopentenylpropynyl and the like.

The term "cycloalkyl" as used herein, refers to an aliphatic ring system having 3 to 10 carbon atoms and 1 or 2 rings. Representative cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornane, bicyclo [2 2] octane and the like The cycloalkyl groups may or may not be substituted with one, two or three substituents independently selected from hydroxy, halo, amino, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, thioatoxy haloalkyl, mercapto, lower alkenyl, and lower alkyl Preferred substituents are independently selected from lower alkyl, lower alkenyl, haloalkyl, halo, hydroxy, and alkoxy The term "(c? alkalkyl) alkyl", as used herein, refers to a cycloalkyl group linked to a lower alkyl radical. Representative examples of (c? alkalkyl) alkyl groups include groups such as, for example, plo, cyclohexylmethyl, cyclopentylmethyl, cyclohexylethyl, cyclopentilethium and the like The term "(c ?cloalkyl) alkenyl", as used herein, refers to a cycloalkyl group attached to a lower alkenyl radical The representative examples of groups (c? cloalkyl) alkenyl include groups such as, for example, cyclohexylethylene, cyclopentylethylene and the like The term "(c? alkalkyl) alkenyl" as used in this document, refers to a cycloalkyl group attached to a lower alkynyl radical. Representative examples of (cycloalkyl) alkynyl groups include groups such as, for example, cyclohexylacetylenyl, cyclopentylpropynyl and the like. The term "dialkylamino", as used herein, refers to groups having the formula -N (R 90) 2, wherein each R 90 is, independently, a lower alkyl group. Representative examples of dialkylamino include dimethylamino, diethylamino, N-methyl-N-isopropylamino and the like. The term "halo", as used herein, refers to F, Cl, Br or I. The term "haloalkenyl", as used herein, refers to a lower alkenyl group in which one or more hydrogen atoms is substituted by a halogen. Examples of haloalkenyl groups include 2-fluoroethylene, 1-chloroethylene, 1,2-difluoroethylene, trifluoroethylene, 1,1,1-trifluoro-2-propylene and the like. The term "haloalkoxy", as used herein, refers to a group having the formula, -OR69, wherein R69 is a haloalkyl group, defined hereinbefore. Examples of haloalkoxy include chloromethoxy, fluoromethoxy, dichloromethoxy, trifluoromethoxy and the like. The term "haloalkyl", as used herein, refers to a lower alkyl group in which one or more hydrogen atoms has been replaced by a halogen including, but not limitations, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, fluoromethyl, chloromethyl, chloroethyl, 2,2-dichloroethyl, pentafluoroethyl and the like. The term "heterocyclic ring" or "heterocyclic" or "heterocycle", as used herein, refers to any 3 or 4 member ring containing a heteroatom selected from oxygen, nitrogen and sulfur; or a ring of 5, 6 or 7 members containing one, two, three or four nitrogen atoms; an oxygen atom; a sulfur atom; a nitrogen atom and a sulfur atom; two nitrogen atoms and one sulfur atom; a nitrogen atom and an oxygen atom; two nitrogen atoms and one oxygen atom; two oxygen atoms in non-adjacent positions; an oxygen atom and a sulfur atom in non-adjacent positions; or two sulfur atoms in non-adjacent positions. The 5-membered ring has 0-2 double bonds and the 6- and 7-membered rings have 0-3 double bonds. The nitrogen heteroatoms may optionally be quaternized. The term "heterocyclic" also includes bicyclic groups in which any of the above heterocyclic rings is fused to a benzene ring or a cyclohexane ring or other heterocyclic ring, such as, for example, indolyl, dihydroindolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, decahydroisoquinolyl, benzofuryl, dihydrobenzofuryl or benzothienyl and the like. Heterocyclic groups include, but are not limited to, groups such as, for example, azepdinyl, azetidinyl, epoxide, oxetanyl, thietanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pipdyl, tetrahydropipyl, pipepdinyl, homopipepdinyl, pyrazinyl, piperazinyl, pipmidinyl, pipdazimide. , oxazolyl, oxazolinyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolinyl, tiazolidmilo, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzotiazohlo, benzoxazolyl, oxetanyl, dihydrofuranyl, tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, thienyl, dihydrothienyl , tetrahydrothienyl, tpazolyl, tpazolinyl, tetrazolyl, tetrazolinyl, isoxazolyl, 1,3-oxadol azol, 2,4-oxadol azol, 1,4-oxadolol, 1, 2, 5-oxadol azole, oxadiazolinyl, 1, 2, 3-t? Ad? Aolol, 1, 2,4-thiadiazolyl, 1, 3,4-t? Ad? Aolol, 1, 2,5-thio-azolyl, thiadiazolinyl, 1,3-dithiolinyl, 1, 2-d? T? Ol? Lo, 1, 3-d? T? Ol? Lo, 1, 3-d? Oxol? N? Lo, didehidrodioxolanilo, 1, 3-oxat? Ol? It ?, oxatiolilo, pipmidyl, benzothienyl and the like The heterocyclic groups also include compounds of formula where X * is -CH2 or -O- and Y * is -C (O) - or [-C (R92) 2-], where R92 is hydrogen or dd-alkyl, where the value of v is 1.2. or 3, such as 1, 3-benzod? oxol, 1, 4-benzod? oxan? lo and the like.

Heterocyclics also include bicyclic rings, such as quinuclidinyl and the like. The heterocyclic groups may or may not be substituted with one to three substituents, each independently selected from lower alkyl, hydroxy, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino and halogen. In addition, the heterocyclic rings containing nitrogen may be N-protected. The term "alkenyl (heterocyclic)", as used herein, refers to a heterocyclic group attached to a lower alkenyl radical including, but not limited to, pyrrolidinyletenyl, morpholinyl ethenyl and the like. The term "(heterocyclic) alkoxy", as used herein, refers to a group having the formula, -OR68, wherein R68 is an alkyl (heterocyclic) group. The term "(heterocyclic) alkyl", as used herein, refers to a heterocyclic group attached to a lower alkyl radical including, but not limited to, pyrrolidinylmethyl, morpholinylmethyl, and the like. The term "alkynyl (heterocyclic)", as used herein, refers to a heterocyclic group attached to a lower alkynyl radical including, but not limited to, pyrrolidinylacetylenyl, morpholinylpropynyl, and the like. The term "oxy (heterocyclic)", as used herein, refers to a heterocyclic group attached to the related molecular moiety through an oxygen atom (-0-).

The term "hydroxiprotective group", "hydroxylprotective group" or "OH-protecting group", as used herein, refers to the groups used to hydroxylate groups in order to avoid unwanted reactions during synthetic procedures. Commonly used hydroxy protectants are described in TH Greene and PGM Wuts, Protective Groups in Orqanic Svnthesis, 2nd edition, John Wiley & Sons, New York (1991) Such hydroxy protecting groups include methylether, substituted methylether, including, but not limited to, methoxymethyl, methylthiomethyl, t-butylthiomethyl, (phenolod? Met? L? L?) Methox? Met? L, benzyloxymethyl, p-methoxybenzyloxymethyl, (4-methox? pheno?) met? l, t-butoxymethyl, 2-methox? ethoxy? met? l, 2, 2,2-tpcloroetox? met? l, 2- (tpmet? ls (1) ethoxymethyl, tetrahydropyranyl, tetrahydroxy-pyranyl tetrahydrofuran, tetrahydrothiofuranyl ether and the like, substituted ethylene ethers, including, but not limited to, 1-ethoxyethyl, 1-methyl-1-methoxyethanol. , 1-met? L-1-benz? Lox? Et? L, 2,2,2-tpcloroethyl, tp m ethi I sil ileii, t-butyl ether and the like, benzyl ether, substituted benzyl ethers, including, but not limited to, -methoxybenzyl, 3,4-d? methoxy? benzyl, on? trobenzyl, p-halobenzyl, p-cyanobenzyl, diphenylmethyl, tphenylmethylether and the like silyl ethers, including, but not limited to, tpmethylsilyl, tpethylshl, tisopropylsilyl, dimethylisopropylsilyl, die tilisopropylsilyl, dimethyl-xylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, t-benzylsilyl, triphenylsilyl, diphenylmethylsilyl ether and the like; esters, including, but not limited to, esters of formate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, phenoxyacetate, pivaloate, benzoate and the like; and similar. Preferred hydroxiprotective groups include substituted methylether, benzylether, substituted benzylethers, silylethers and esters.

The term "hydroxyalkyl", as used herein, refers to a group having the formula, -R85-OH, where R65 is an alkylene group. The term "leaving group", as used herein, refers to a group that is easily displaced from the compound by a nucleophile. Examples of leaving groups include a halide (eg, Cl, Br or I) or a sulfonate (eg, mesylate, tosylate, triflate and the like) and the like.

The term "N-protecting group" or "N-protected", as used herein, refers to the groups that are used to protect the N-terminus of an amino acid or peptide or to protect an amino group against non-reactive desired during synthetic procedures. The commonly used N-protecting groups are described in T. H. Greene and P.G. M. Wuts, Protective Groups in Orqanic Svnthesis. 2nd edition, John Wiley & Sons, New York (1991). The N-protecting groups comprise acyl groups, such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2- chloroacetyl 2-bromoacetyl, tpfluoroacetyl, tpcloroacetyl, phthalyl, o-nitrophenoxyacetyl, a-chlorobutyl, benzoyl, 4-chlorobenzoyl? 4-bromobenzoyl 4-n-trobenzoyl and the like, sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl and the like, carbamate-forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-n? trobenc? lox? carbon? lo, p-bromobenzyloxycarboniio, 3,4-d? metox? benc? lox? carb? lo, 3, 5-dimethoxy-benzyloxycarbonyl, 2,4-d? methox? benc? lox? carbon? lo, 4-methoxybenzyloxycarbonyl, 2-n? tro-4, 5-d? methox? benc? lox? carbon? lo, 3, 4, 5-tr? Metox? Benc? Lox? Carbon? Lo, 1 - (p? Fen? L? L) - 1 -methol to rbonyl, a, ad? Met? L-3, 5- d? methox? -benzylcarbonyl, benzhydiploxycarbonyl, t-butyloxycarbonyl, dnsopropyl-methoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, halo-oxycarbonyl, 2,2-t-chloroethoxycarbonyl, phenoxycarbonyl, 4-n-tro-phenoxyl? carbonyl, fluorenol-9-methoxylcarbonyl, cyclopentyloxycarbonyl, adamanyl-1-oxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like, alkyl groups such as benzyl, tphenylmethyl, benzyloxymethyl and the like, and silyl groups such as trimethylsilyl and the like Preferred N-protecting groups are formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz). The term "thioalkoxy", as used herein, refers to to groups possessing the formula -SR98, where R98 is an alkyl group The preferred R98 groups are lower alkyl groups The term "thio-substituted alkyl", as used herein, refers to an alkyl radical to which a thiol group (-SH) is attached. As used herein, the terms "S" and "R" configuration are as defined by I U PAC 1974 in Recommendations for Section E, Fundamental Stereochemistry, Puré Appl. Chem. (1976) 45, 13-30. The compounds of the invention may comprise asymmetrically substituted carbon atoms. As a result, all stereoisomers of the compounds of the invention are considered to be included in the invention, including racemic mixtures, mixtures of diastereomers, as well as individual optical isomers, including simple enantiomers and diastereomers of the compounds of the invention. invention are substantially free of their enantiomers or other diastereomers. When it is said "substantially free" it means that they are more than about 80% free of other enantiomers or diastereomers of the compound, more preferably more than about 90% free of other enantiomers or diastereomers of the compound, still more preferably greater than about 95% free of other enantiomers or diastereomers of the compound, more preferably more than about 98% free of other enantiomers or diastereomers of the compound and most preferably more than about 99% free of other enantiomers or diastereomers of the compound.

In addition, compounds comprising the possible geometric isomers of carbon-carbon double bonds and carbon-nitrogen double bonds are also considered to be included in this invention. The individual stereoisomers of the compounds of this invention can be prepared by any of the methods that are commonly known to those skilled in the art. These methods include stereospecific synthesis, chromatographic separation of diastereomers, chromatographic resolution of enantiomers, conversion of enantiomers of an enantiomeric mixture into diastereomers and subsequent chromatographic separation of the diastereomers and regeneration of the individual enantiomers, enzymatic resolution and the like.

Stereospecific synthesis comprises the use of appropriate chiral starting materials and synthetic reactions that do not cause racemization or reversal of stereochemistry at chiral centers. Diastereomeric mixtures of the compounds resulting from a synthesis reaction can often be separated by chromatographic techniques that are well known to those skilled in the art. The chromatographic resolution of enantiomers can be carried out on chiral resins for chromatography. Chromatographic columns containing chiral resins are commercially available. In practice, the racemate is placed in solution and it is loaded into the column containing the stationary chiral phase. The enantiomers are then separated by H PLC. The resolution of enantiomers can also be carried out by conversion of the enantiomers of a mixture into the diastereomers by reaction with chiral auxiliaries. The resulting diastereomers can then be separated by column chromatography. This technique is especially useful when the compounds to be separated contain a carboxyl, amino or hydroxyl group which will form a salt or a covalent bond with the chiral auxiliary. Amino acids, organic carboxylic acids or chirally pure organosulfonic acids are especially useful as chiral auxiliaries. Once the diastereomers are separated by chromatography, the individual enantiomers can be regenerated. Often, it is possible to recover the chiral auxiliary and reuse it. Enzymes, such as esterases, phosphatases and lipases, may be useful for the resolution of enantiomer derivatives in an enantiomeric mixture. For example, an ester derived from a carboxyl group can be prepared in the compounds to be separated. Some enzymes selectively hydrolyze only one of the enantiomers in the mixture. The enantiomerically pure acid can then be separated from the non-hydroxylated ester. In addition, the solvates and hydrates of the compounds of Formula I and II and III are also considered included in this invention. When any variable (for example R, R2, R3, m, n, etc.) appears more than once in any substituent or in the compound of Formula I or II or II or in any other formula of the present document, its definition in each case is independent of its definition any other occurrence. In addition, combinations of substituents are permitted only if such combinations result in stable compounds. Stable compounds are compounds that can be isolated to a degree of useful purity from a reaction mixture. This invention is intended to encompass the compounds of Formula I and II and III when prepared by synthetic processes or by metabolic processes. The preparation of the compounds of the invention by metabolic processes includes those processes that take place in the body of the human or animal (in vivo) or the processes that take place in vitro. The compounds of the invention can be prepared according to the methods that are described in Schemes 1-5 as shown below. In all schemes, methods are illustrated where R1 is a carboxylic acid substituent or carboxylic acid ester. Those skilled in the art will understand that it is possible to (a) obtain other R substituents of the carboxylic acid group or the carboxylic acid ester group, (b) introduce other R substituents by methods similar to those used to introduce the carboxylic acid group or the group carboxylic acid ester or (c) introducing other substituents R1 with other methods generally known in the art.

In addition, in all schemes, methods are illustrated where R4, R6, R7, R8, R9 and R10 are hydrogen Those skilled in the art will understand that compounds can be prepared where one or more of these substituents is other than hydrogen by analogous methods those described in the schemes or by other methods generally known in the art. In addition, methods for obtaining compounds of the invention having the preferred relative stereochemistry are illustrated in all schemes. Those skilled in the art will understand that compounds of the invention that possess a different relative stereochemistry can be prepared by methods analogous to those described in the schemes or with other methods generally known in the art. Furthermore, in all schemes, methods are illustrated where X is -C (= 0) -NH- Those skilled in the art will understand that other X groups can be prepared by methods analogous to those described in the schemes or with other known methods in general. In the art As shown in Scheme 1, the reaction of acrolein with the ester of the N-protected a-amino acid 1 (P1 is an N-protecting group, preferably a benzyl group or the like and P2 is a protecting group of carboxylic acid, preferably a t-butyl group or the like) in an inert solvent (for example, toluene and the like) in the presence of an acid catalyst (for example, acid acetic and similar), followed by neutralization with a base (for example, with triethylamine or similar) and separation of the isomers by chromatography, allows to obtain the substituted pyrrolidine 2_. The reduction of the aldehyde group in an alcohol with an aldehyde-reducing agent in alcohol (for example, sodium borohydride or the like) in an inert solvent (for example, methanol or the like), followed by chromatographic separation of the isomers makes it possible to obtain the alcohol 3_. The alcohol 3. can be protected with a hydroxiprotective group P3 (preferably with a silyl protecting group, for example, t-butyldimethylsilyl or the like) using the standard alcohol protection methods to obtain 4. Oxidation of the vinyl group of compound 4 in an aldehyde is carried out by reacting compound 4 with Os04 and N-methylmorpholine-N-oxide to give the corresponding diol. The diol is then treated with sodium periodate to obtain the 5-aldehyde. The R3 substituents can be introduced by a reaction of the aldehyde 5 with a Grignard reagent (eg, R3MgBr or the like) to give the alcohol 6. The oxidation of the alcohol 6. (eg, Swern oxidation or the like) provides the Ketone 7- A reductive amination of the ketone 7_ (For example, by reaction with ammonium acetate and sodium cyanoborohydride in metapol or the like) allows obtaining the amine 8 Amine 8 can be further functionalized to complete the introduction of the substituent R2-X - (for example, by reaction of the amine with an acylating agent, such as acetic anhydride or the like or with other acylation methods), followed by chromatographic separation of the diastereomers to obtain 9a. The other diastereomeric amine (9b) can also be isolated and further transformed according to Scheme 1. Removal of the hydroxiprotective group P3 (for example, by reaction with a source of fluoride ions, such as tetrabutylammonium fluoride or the like, when P3 is a silyl protecting group) allows to obtain the alcohol 10. The transformation of the hydroxy group of the alcohol 10. allows introducing various Y substituents. For example, the alkylation of the hydroxy group provides the ethers eleven . The N-deprotection (for example, where P1 is a benzyl group, by hydrogenation) makes it possible to obtain 127 followed by hydrolysis of the ester (for example, with an acid such as HCl), provides the compound 12 of the invention. hydroxy group of 1P_ (for example, oxidation of Swern or similar) provides aldehyde 13. Oxidation of aldehyde 13 (for example, with NaCl02 or the like) allows to obtain the carboxylic acid 14. The carboxylic acid substituent of 14. can be used to introduce various different functional groups into the Y substituent. For example, the carboxylic acid can be esterified (for example, by reaction with diazomethane or with ethanol and DCC or the like) or the carboxylic acid or an activated derivative thereof can be reacted with amines to give 1_5. (where -C (= 0) -R22 represents an ester or an amide). N-deprotection (for example, where P is a benzyl group, for hydrogenation) allows to obtain 16 ', followed by hydrolysis of the ester (for example, with an acid such as HCl), whereby the compound 16"of the invention is obtained The derivatives of the aldehyde group of 13. or of the carboxylic acid group of 14. can be used to introduce substituents Y which are -CN or various heterocycles, according to methods known to those skilled in the art and in accordance with the specific methods exemplified herein.The reaction of aldehyde 13. with reagents of Grignard-lower alkyl or lower alkenyl, followed by oxidation (e.g., Swern oxidation or the like), provides ketones i wherein R22 is lower alkyl or lower alkenyl N-deprotection (e.g., where P1 is a benzyl group) , by hydrogenation) results in 18 ', followed by hydrolysis of the ester (for example, with an acid, such as HCl), whereby compound 18"of the invention is obtained.

The compounds wherein the substituent Y is an amino group or a derivative of an amino group can be prepared as shown in Scheme 2. Oxidation of the aldehyde 2 (for example, with AgO or NaCl02 or the like) provides the carboxylic acid. .. The rearrangement of Curtius carboxylic acid 1_9_ (for example, by reaction with DPPA, Et3N and benzyl alcohol or the like), followed by chromatographic separation of the diastereomers, allows to obtain 20. where P4 is an N-protecting group (for example, benzyloxycarbonyl or the like). The analogous transformations of those which made it possible to convert compound 4 to compounds 9a and 9b in Scheme 1, allow the conversion of 20 in 21 a and 21 b. which can be separated by chromatography. The elimination of the protective group P4 (for example, by means of selective hydrogenation) makes it possible to obtain 22. The additional derivatization of the amino group makes it possible to introduce substituents Y which are amine derivatives. N-deprotection (e.g., where P1 is a benzyl group, by hydrogenation), followed by hydrolysis of the ester (e.g., with an acid such as HCl), provides compounds of the invention where Y is amino or an amine derivative. The olefination of aldehyde 13. (for example, with Ph3PCH2 or the like), followed by hydrogenation (causing N-deprotection (for example, where P1 is a benzyl group)) and saturation with olefins, followed by hydrolysis of the ester (e.g. with an acid such as HCl), provides compounds of the invention wherein Y is lower alkyl. As shown in Scheme 3, the oxidation of the vinyl group of compound 4 in a diol (for example, with 0s04 and N-methylmorpholine-N-oxide or the like) makes it possible to obtain diol 23. Removal of the N-protecting group P1 (for example, where P1 is a benzyl group, by hydrogenation) provides pyrrolidine 24. The new protection with an N-protecting group of labile acid P5 (for example, t-butoxycarbonyl or the like) allows to obtain 25. The transformation of the compound 25. in the aldehydes 26a and 2b can be carried out analogously to the conversion of the compound 4a into the compound 10 and the compound 1_0 into the compound ± 3_ as shown in Scheme 1. The 2ßa and 2ßb compounds can be separated by chromatography. Olefination of 26a (for example, with Ph3PCH2 or triphenylphosphine / methylene chloride / n-BuLi, or rPh3P + CH2CH3 / KOtBu, or the like) provides compound 27. where Y is an olefinic substituent. The N-deprotection of the protecting group P5 and the hydrolysis of the ester, under acidic conditions, makes it possible to obtain compounds of the invention wherein Y is an olefinic substituent. In yet another alternative method shown in Scheme 4, the hydroxy group of the alcohol 3. is protected with a hydroxy-protecting group of labile base P6, (eg, acetyl or the like) to give the compound 29. Oxidation of the vinyl group of 29 with OSO and N-methylmorpholine-N-oxide provides the diol 30 .. Removal of the protective group P1 (for example, by hydrogenation or the like) allows obtaining pyrrolidine 3_1. The new protection with a N-protecting group of labile acid P5 (for example, t-butoxycarbonyl or the like) provides the compound 32 .. Selective protection of the primary alcohol of 32. with a hydroxy protecting group P7 (eg, a silyl protecting group such as triisopropylsilyl or the like) provides the compound 33 .. The oxidation of 33. (for example, with Swern oxidation or the like) provides the ketone 34. The reductive amination of the ketone 34. (for example, by reaction with ammonium acetate and sodium cyanoborohydride in methanol or the like) allows the amine to be obtained 3_5 Amine 35. can be further functionalized in order & & amp; C * to complete the introduction of the substituent R -X- (for example, by reaction of the amine with an acylating agent, such as acetic anhydride or the like or by other acylation methods), followed by chromatographic separation of the diastereomers to obtain 36a .. The other diastereomeric amine (36b) can also be isolated and further transformed according to this scheme. Selective removal of the hydroxiprotective group P6 at 36a (for example, with K2CO3 in methanol or the like) provides the alcohol 37. Oxidation of the alcohol in an aldehyde (for example, with an oxidation of Swern or the like) provides the compound 38_. The aldehyde can serve as a precursor to various Y substituents in the compounds of the invention. For example, olefination of 38. (for example, with Ph3PCH2 or triphenylphosphine / methylene chloride / n-BuLi, or rPh3P + CH2CH3 / KOtBu, or the like) allows obtaining 3 where Y is an olefinic substituent. Removal of the hydroxyprotective group P7 (for example, with a source of fluoride ions such as tetrabutylammonium fluoride or the like) makes it possible to obtain the alcohol 40. The alcohol can serve as a precursor of various substituents R3 in the compounds of the invention. For example, the alcohol of 40. can be oxidized in an aldehyde (for example, with Dess-Martin oxidation or the like) to give compound 41. The aldehyde 41 can react with Grignard reagents (R14Mg Br or the like ) or other organometallic reagents (for example, organolithium reagents, such as R 4Li or the like) to give 42 as a mixture of diastereomers of the alcohol which can be separated chromatographically to give the major isomer 42a and the other isomer 42b. The isomer 42a or the mixture of 42 isomers can be oxidized (for example, with Dess-Martin oxidation or the like) to give the ketone 43. The reduction of the ketone 43 (for example, with sodium borohydride in ethanol) or similar) provides alcohol 42b as the main isomer, which can be isolated by chromatography. The N-deprotection of the protecting group P5 and the hydrolysis of the ester, under acidic conditions, makes it possible to obtain the compounds of the invention 44a or 44b, respectively, where Y is an olefinic substituent. The alkylation of the alcohol 42a or 42b provides the ethers 45a or 46b. respectively. The N-deprotection of the protecting group P5 and the hydrolysis of the ester, under acidic conditions, makes it possible to obtain the compounds of the invention 48a or 48b, respectively, where Y is an olefinic substituent. As shown in Scheme 5, the reaction of the ketone 43 with Grignard reagents (R37aMg Br or the like) or other organometallic reagents (eg, organolithium reagents, such as R37aLi or the like) provides the alcohols 46a and 46b as a mixture of diastereomers of alcohol that can be separated chromatographically. The N-deprotection of the protecting group P5 and the hydrolysis of the ester, under acidic conditions, makes it possible to obtain the compounds of the invention 47a or 47b, respectively, where Y is an olefinic substituent. The alkylation of the alcohol 46a or 46b provides the ethers 49a or 49b. respectively. The N-deprotection of the protective group Ps and the hydrolysis of the ester, under acidic conditions, makes it possible to obtain the compounds of the invention 50a or 50b, respectively, where Y is an olefinic substituent. Esters or prodrugs of the compounds of the invention can be prepared by methods known in the art.

SCHEME 1 PO--, HO -O ° p2 O ^ T? OP2 H2Ns T ° P 6 7 8 9a 9b SCHEME 1 (continued) ester or an amda SCHEME 1 (continued) OR 16" 17 itr R22 is lower alkyl or lower alkenyl 18" . -yj zz.zUÍ? ^ z.

SCHEME 2 19 20 21a 21b 22b 22a ESQ UEMA 3 26a 26b 27 28 And it's an alkene SCHEME 4 31 32 P? - SCHEME 4 (continued) 37 38 39 And it's an alkepo 40 or a haloalkene 41 SCHEME 4 (continued) 42a 42b 48a 48b iy, and SCHEME 4 (continued) 44b SCHEME 5 SCHEME 5 (continued) The other compounds of the invention can be easily prepared from the compounds described herein using techniques known in the chemical literature. The necessary methods are known and easily practiced by those skilled in the art. The key intermediates for the preparation of the compounds of the invention include the following compounds: (1) where P1 is an N-protecting group (preferably, a benzyl group or a substituted benzyl group) and P2 is a carboxylic acid protecting group (preferably, a lower alkyl group, especially t-butyl); preferably, P and P2 can be deprotected / removed selectively; or a salt thereof; (2) pJo - -. where P1 is an N-protecting group (preferably, a group benzyl or a substituted benzyl group) and P2 is a carboxylic acid protecting group (preferably a lower alkyl group, especially t-butyl): and P3 is hydrogen or a hydroxy protecting group (preferably, an acylprotective group, for example, acetyl and the like, or a silyl protecting group, eg, t-butyldimethylsilyl and the like); Preferably, P1, P2 and P3 can be selectively deprotected / deleted; or a salt thereof; (3) P HN, where P1 is an N-protecting group (preferably, a benzyl group or a substituted benzyl group) and P2 is a carboxylic acid protecting group (preferably, a lower alkyl group, especially t-butyl); and P4 is hydrogen or an N-protecting group (preferably, a N-carbamate protecting group, for example, benzyloxycarbonyl and the like); Preferably, P1, P2 and P4 can be selectively deprotected / deleted; or a salt thereof, (4) P? - where P5 is an N-protecting group (preferably, an N-protecting group of labile acid, such as t-butyloxycarbonyl and the like) and P2 is a carboxylic acid protecting group (preferably, a lower alkyl group, especially t- butyl), and P6 is hydrogen or a hydroxiprotective group (preferably, a labile base hydroxiprotective group, such as acetyl and the like); and P7 is a hydroxy protecting group (preferably, a silyl protecting group, such as triisopropylsilyl and the like); Preferably, P2, P5, P6 and P7 can be selectively deprotected / deleted; or a salt thereof; and (5) PO - -. where P5 is an N-protecting group (preferably, an N-protecting group of labile acid, such as t-butyloxycarbonyl and the like) and P2 is a carboxylic acid protecting group (preferably, a lower alkyl group, especially t- butyl); and P6 is hydrogen or a hydroxy protecting group (preferably, a labile base hydroxiprotective group, such as acetyl and the like); and P7 is hydroxyprotective group (preferably, a silyl protecting group, such as triisopropylsilyl and the like); and R2 was previously defined herein (preferably, lower alkyl or lower haloalkyl, more preferably, methyl or trifluoromethyl); Preferably, P2, P5, P6 and P7 can be selectively deprotected / deleted; or a salt of them. All patents, patent applications and references to literature cited herein are incorporated herein by reference in their entirety. In the case of any existing Incoherence, the present description prevails, including definitions. Reagents necessary for the synthesis of the compounds of the invention are readily available from numerous commercial sources such as Aldrich Chemical Co. (Milwaukee, Wl, U.S.A.); Sigma Chemical Co. (St. Louis, MO, USA); and Fluka Chemical Corp. (Ronkonkoma, NY, USA); Alfa Aesar (Ward Hill, MA 01835-9953); Eastman Chemical Company (Rochester, New York 14652-3512); Lancaster Synthesis Inc. (Windham, N H 03087- 10 9977); Spectrum Chemical Manufacturing Corp. (Janssen Chemical) (New Brunswick, NJ 08901); Pfaltz and Bauer (Aguabury, CT 06708). Compounds that are not commercially available can be prepared by methods known in the chemical literature. The following examples will serve to further illustrate the preparation of the compounds of the invention, without limitations.

Example 1 (±) - (2R, 3R, 5R, 1 'S) -2- (1-Acetamido-3-epentpentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid hydrochloride. 1A. f-Butyl Ester of Acid (±) - (2S.3R.5R) - and (±) - (2S.3S.5R) -1-Benzyl-2-vinyl-3-formyl-pyrroli in-5-carboxyl ( 8: 1 ratio). Acrolein (8 mL, 120 mmol) was added to a solution of f-butyl N-benzylglycinate (4.34 g, 19.6 mmol) and acetic acid (5 drops) in toluene (100 mL). The solution was heated to reflux. After 1 hour, the reaction was cooled to about 50 ° C and an additional 3 mL of acrolein was added. The reaction was refluxed for a further 2 hours and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% ethyl acetate / hexanes to give a mixture of f-butyl esters of (+) - (2S, 3R, 5R) - and (±) - (2S, 3S) acid , 5R) -1-benzyl-2-vinyl-3-formyl-pyrrolidine-5-carboxylic acid (yield: 2.78 g, 45%). The aldehyde mixture was equilibrated at a ratio of 8: 1 by stirring the crude product with triethylamine (0.5 mL) in ethyl acetate at room temperature followed by evaporation of the solvents.

H NMR (CDCl 3) (major isomer only): 51.45 (s, 9H), 2.26 (m, 1H), 2.69 (m, 1H), 3.49 (dd, J = 7.8, 3.0 Hz, 1H), 3.61 (d, J = 13.5 Hz, 1H), 3.93 (m, 1H), 3.94 (d, J = 13.5 Hz, 1H), 5.22-533 (two dd, 2H), 5.7 (ddd, J = 17.7, 10.2, 7.8 Hz, 1H), 7.21-7.35 (m, 5H), 9.71 (d, J = 1.2 Hz, 1H). MS (M + H) + = 316. 1 B. f-Butyl Ester of Acid (±) - (2S, 3R, 5R) -1-Benzyl-2-vinyl-3- (hydroxymethyl) -pyrrolidine-5-carboxylic acid. A solution of the 8: 1 mixture of (±) - (2S, 3R, 5R) - and (±) - (2S, 3S, 5R) -1-benzyl f-butyl ester was cooled to 0 ° C. -2-vinyl-3-formylpyrrolidine-5-carboxylic acid (6.0 g, 19.0 mmol), prepared according to the method described in Example 1A, in 100 mL of methanol, and treated with sodium borohydride (0.72 g). , 19.0 mmol). The mixture was stirred for 0.5 hour, allowed to take room temperature, and stirred for an additional hour. The reaction was set with aqueous ammonium chloride solution, and the solvent was evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was dried over MgSO 4, filtered and concentrated in vacuo. The residual oil was purified by chromatography on silica gel using a gradient of 20-30% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 4.0 g, 66%). 1 H NMR (CDCl 3): 51.46 (s, 9 H), 1.80 (m, 1 H), 2.16 (m, 1 H), 2.39 (m, 1H), 2 54 (m, 1H), 348-3.53 (m, 2H), 3 08 (d, 2H) 3.91 (d, 2H), 5.17-5.22 (m, 2H), 5.70 (m, 1H), 7 23-7.34 (m, 5H). MS (M + H) * = 318. 1 C. f-Butyl Ester of Acid (±) - (2S.3R.5R) -1-Benzyl-2-vinyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid. A solution of (±) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3- (hydroxymethyl) -pyrrolidine-5-carboxylic acid (3.6 g, 11.4 mmol), tert-butyldimethylsilyl chloride (3.7 g) , 24.5 mmol) and imidazole (2.8 g, 41.2 mmol) in 80 mL of DMF was stirred at room temperature for 1.5 hours. The reaction was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% ethyl acetate / hexanes to give the title compound, as a colorless oil (yield: 3.5 g, 71%). 1 H NMR (CDCl 3): 50.02 (d, 6H), 0.86 (s, 9H), 1.43 (s, 9H), 1.67 (ddd, 1H), 2.11 (, 1H), 2.28 (m, 1H), 340-3.70 (m, 6H), 3.90 (d, 2H), 5.11-5.19 (m, 2H), 5.69 (ddd, 1H), 7.20-7.30 (m, 5H). MS (M + H) * = 432.

TBDMSO- ,, 1 D. (t) - (2R, 3R, 5R) -1-Benzyl-2-formyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid t-butyl ester. Osmium tetroxide (20 mg) was added to a room temperature solution of (±) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3- (f-butyl-dimethyl) t-butyl ester. L-oxymethyl) -pyrrolidine-5-carboxylic acid (3.5 g, 8.12 mmol) in 60 mL of 8: 1 acetone / water and N-methylmorpholine N-oxide (3.0 g, 25.6 μmol). The reaction mixture was stirred at room temperature for 6 hours and was set with saturated aqueous Na2S203 solution. The mixture was stirred for a further 10 minutes and the solvent was removed. The brownish residue was partitioned between dichloromethane and water. The organic layer was dried over MgSO4 and concentrated in vacuo to give the intermediate diol as an oil (~ 3.8 g) which was used without further purification. MS (crude): (M + H) + = 466 The crude diol was dissolved in 6: 1 tetrahydrofuran (TH F) / water (50 mL), it was treated with sodium periodate (3.0 g, 14.0 mmol). The mixture was stirred at room temperature for 1 hour and diluted with ethyl acetate, washed with water, dried over MgSO, filtered, and concentrated in vacuo. The crude aldehyde was purified by chromatography on silica gel using 3% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 1.6 g, 46%). 1 H NMR (CDCl 3): 50.03 (d, 6 H), 0.86 (s, 9 H), 1 46 (s, 9 H), 1.72 (m 1 H), 2 26-2.45 (m, 2 H), 3.53-371 (m, 5H), 3 84 (d, 1H), 3.93 (d, 1H) 7.27-7.31 (m, 5H), 9.32 (d, 1H) MS (M + H) * = 434. 1E. acid t-butyl ester (±) - (2R.3R.5R) -1-Benzyl-2- (1-oxo-3-ethyl-l-3-yl-butyldimethylsilyloxymethyl) -pyrrolidin-5 -carboxylic A dry flask with magnesium content (0.14 g, 5.83 mmol) was charged, under argon, with 10 mL of dry THF and 3 drops of dibromoethane. This was followed by the addition of 1-bromo-2-ethylbutane (0.95 g, 5.83 mmol). The reaction mixture was heated to reflux for 45 minutes, until most of the magnesium had reacted. The reaction mixture was cooled to -30 ° C and (±) - (2R, 3R, 5R) -1-benzyl-2-formyl-3- (f-butyldimethylsilyloxymethyl) t-butyl ester was added dropwise. ) -pyrrolidine-5-carboxylic acid (0.5 g, 1.15 mmol) in THF (6 mL). The reaction was slowly warmed to -10 ° C, over a period of about 2 hours, and was fired with aqueous solution of ammonium chloride. The resulting slurry was diluted with ethyl acetate and washed with water, brine, and dried over MgSO4 and concentrated. The crude alcoholic product, an oil (~ 0 85 g), was used without purification additional MS (M + H) + = 520. A solution of oxalyl chloride (2.5 mL, 2M in C H2CI2) in mL of anhydrous dichloromethane was prepared and maintained under a nitrogen atmosphere at -78 ° C. DMSO (0.77 μL, 9.83 mmol) was slowly added to the solution. The mixture was stirred for 15 minutes, treated with the crude alcohol prepared above, about 0.85 g, in 5 mL of anhydrous dichloromethane. The solution was stirred for 1 hour and triethylamine (2.3 mL, 16.4 mmol) was slowly added to the reaction mixture. The solution was allowed to slowly take room temperature and diluted with dichloromethane. The organic layer was washed with water, dried over MgSO4, and concentrated. The residue was purified by chromatography on silica gel using 3% ethyl acetate / hexanes to give the title compound, as an oil (yield: 0.35 g, 66%).

MS (M + H) + = 518. 1 F. (t) - butyl ester of the acid (±) - (2R.3R.5R.1 'R) - and (±) - (2R .3R.5R. 1' S) -1-Benzyl-2- (1 amino-3-ethyl) pentyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid. A solution of t-butyl ester of (±) - (2R, 3R.5R) -1-benzyl-2- (1-oxo-3-ethyl) pentyl-3- (f-) acid was heated at reflux for 24 hours. but? ld? met? l? l? lox? met?) -pyrrolidone-5-carboxylic (O 20 g, 0 39 mmol), ammonium acetate (30 equiv.) and sodium cyanoborohydride (10 equiv) in 5 mL of methanol with the occasional addition of 60 additional equivalents of ammonium acetate and 20 additional equivalents of sodium cyanobohydride The solvent was evaporated The resulting residue was partitioned between dichloromethane and water The organic layer was dried on MgSO4, filtered, and concentrated. The product was purified by chromatography on silica gel using 30-50% ethyl acetate / hexanes to give the title compound as a colorless oil (yield 130 mg, 64%) 1H NMR (CDCl 3) 5 730 (m, 5H), 491 (s, 1H), 3 53 (m, 2H), 308 (m, 1H), 2 88 (m, 1H), 2 35 (m, 1H), 1 85 (, 1H), 1 44 (s, 9H), 1 20-1 40 (m, 7H), 0 88 (s, 9H), 0 85 (m, 6H), 003 (s, 6H) MS (M + H) * = 519 1G t-butyl ester of acid (±) - (2R, 3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-et? L) pent? L-3-íf- but? ld? met? l? l? lox? met?) -pyrrolidone-5-carboxylic acid A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'R) - and (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-am? No-3-et? L) pent? L-3- (f- but? ld? met? l? l? lox? met?) -pyrrolidone-5-carboxyl? co (110 mg, 021 mmol) and acetic anhydride (214 mg, 2 1 mmol) in 10 g. mL of diethylomethane for 1 hour. The excess acetic anhydride and solvent were removed in vacuo. The residue was purified by chromatography on silica gel using 30% ethyl acetate / hexanes to give the title compound as a white solid (yield: 85 mg, 72%). H NMR (CDCl 3) 5 7.28 (m, 5H), 5.14 (d, J = 14Hz, 1H), 4.36 (m, 1H), 3.95 (m, 2H), 3.62 (m, 1H), 3.52 (m, 1H ), 3.45 (m, 1H), 2.98 (m, 1H), 1.98 (s, 3H), 1.60 (m, 2H), 1.43 (s, 9H), 1.20-1.40 (m, 7H), 0.88 (s, 9H), 0.80 (m, 6H), 0.04 (s, 6H) MS (M + H) * = 561. 1 HOUR. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (hydroxylmethyl) -pyrrolidip-5 -carboxylic A solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-ethyl) pentyl-3- (f-butyldimethyl-silyloxymethyl) t-butyl ester was prepared. ) -pyrrolidine-5-carboxylic acid (85 mg, 0.15 mmol) in dry THF (5 mL) and maintained at room temperature under a nitrogen atmosphere. Tetrabutylammonium fluoride (1M in THF, 0.23 mL) was slowly added to the solution. The reaction mixture was stirred for 1 hour. The solvent was removed in vacuo and the residue was purified by chromatography on silica gel using 30-50% ethyl acetate / hexanes to give the title compound as a white foam (yield: 41 mg, 61%). && , fc 1 H NMR (CDCl 3) 5 7.20-7.35 (m, 5 H), 5.20 (d, J = 14 Hz, 1 H), 428 (m 1 H), 4.93 (m, 2 H), 3.65 (m, 2 H), 3.50 (m, 1H), 323 (, 2H), 2.22 (m, 2H), 1.98 (s, 3H), 1.62 (m, 1H), 1.43 (s, 9H), 1.15-1.40 (m, 7H), 0.80 (m, 6H) MS (M + H) * = 447. 11 (+) - (2R, 3R, 5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidin-5-butyl ester carboxylic A mixture of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (hydroxymethyl) - t-butyl ester was heated to reflux. pyrrolidine-5-carboxylic acid (40 mg, 09.0 mmol) and silver oxide (200 mg, 0.90 mmol) in 3 mL of iodomethane for three hours. The reaction was cooled, filtered, and the solvent removed in vacuo to give the title product as a crude oil. MS (M + H) * = 461.

U (t) - butyl ester of (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid. A mixture of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3- (methoxymethyl-pyrrolidin) t-butyl ester Crude carboxylic acid (32 mg, 0.07 mmol), prepared according to the method described in Example 11, and ammonium formate (130 mg, 2.1 mmol) in ethanol (5 mL) was heated to reflux in the presence of a catalytic amount of 10% palladium on activated charcoal for 1.5 hours The reaction was filtered and concentrated in vacuo The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes followed by 10% methanol / dichloromethane to give the title compound as a colorless oil (yield: 16 mg, 47%) MS (M + H) * = 371.

MeO- ,. 1K Acid chlorhydrate (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethylpephenyl-3- (methoxymethylpyridine-5-carboxylic acid). acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -2- (1- acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrole d-5-carboxylic acid (15 mg) was dissolved in 6 N HCl in water (1 mL) and stirred at room temperature for 3 hours. . The solvent was removed under high vacuum to give the title compound as a white solid. 1H NMR (d6-DMSO) d 8.10 (d, J = 14Hz, 1H), 4.28 (m, 1H), 4.18 (m, 1H), 3. 45 (m, 1H), 3.22 (s, 3H), 2.47 (m, 1H), 2.38 (m, 1H), 1.90 (m, 1H), 1. 88 (s, 3H), 1.15-1.42 (m, 7H), 0.82 (t, J = 12.5Hz, 3H), 0.79 (t, J = 12.5Hz, 3H) MS (M + H) * = 315, (M-H) - = 313.

Example 2 (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) -pentyl-3-methoxycarbonyl-pyrrolidin-5-carboxylic acid hydrochloride. 2A. acid t-butyl ester (± - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-formyl-pyrrolidin-5-carboxyl? co. A solution of oxalyl chloride (0.11 mL, 2M in CH2Cl2) in 5 mL of anhydrous dichloromethane and kept under a nitrogen atmosphere, at -78 ° C. DMSO (32 mg, 0.42 mmol) was slowly added to the solution. The mixture was stirred for 15 minutes, treated with t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1- benzyl-2- (1-acetamido-3-yl) pentyl-3-hydroxymethyl-pyrro lidin-5-carboxylic acid (38 mg, 0.085 mmol) in 5 mL of dichloromethane. The solution was stirred for 1 hour and triethylamine (86 mg, 0.85 mmol) was slowly added to the reaction mixture. The solution was allowed to take room temperature and diluted with dichloromethane. The organic layer was washed with water and brine, dried over MgSO 4, filtered and concentrated. The residue was purified by chromatography on silica gel using 3% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 39 mg, 97%). 1 H NMR (CDCl 3) 5 9.68 (d, J = 1.0 Hz, 1 H), 7.28 (m, 5 H), 5.06 (d, J = 14 Hz, 1 H), 4.38 (m, 1 H), 4.10 (m, 1 H), 3.75 (m, 2H), 3.45 (m, 1H), 2.62 (m, 1H), 2.20 (m, 2H), 1.98 (s, 3H), 1.42 (s, 9H), 1.25-1.40 (m, 7H) , 0.82 (m, 6H) 15 MS (M + H) * = 445. 2B. t-butyl ester of (±) - (2R.3R.5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid. 20 A solution of NaCl02 (0.16 g) and NaH2P? 4.H20 (0.17 g) in water (1 mL) was added to a solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-formyl-? Irrolidin-5- carboxylic acid (35 mg, 0.079 mmol) and 2-methyl-2-butene (0.5 mL) dissolved in t-BuOH (1.5 mL) and acetonitoplo (1.5 mL) at 0 ° C. After 1 hour the reaction was set with 10% aqueous Na2S203 solution and extracted with dichloromethane. The organic layer was washed with water and brine, dried (MgSO4) and concentrated to give the title product (yield: -30 mg). MS (M + H) * = 461. 2 C. acid t-butyl ester (±) - (2R.3R.5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid .

A solution of Diazald ™ (0.5 g, 2.33 mmol) in 5 mL of ether was added slowly to an aqueous solution of KOH (0.5 g in 1 mL of water) and 1 mL of ethanol was maintained at 65 ° C. Diazomethane was distilled into a receiver vessel charged with a solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3 acid. -carboxyl-pyrrolidine-5-carboxylic acid (30 mg, 0.065 mmol) in 3 mL of THF. The receiving vessel was cooled to 0 ° C in an ice / water bath. The condenser was cooled with dry ice / acetone and 3 mL of ether were added to the distillation vessel until the distillate was colorless. The reaction was sed for additional 0.5 hours at 0 ° C. The yellowish reaction mixture was fired with acid acetic acid (0.1 mL) and diluted with ethyl acetate. The organic layer was washed with 10% NaHCO 3 and brine, dried with MgSO 4 and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 20 mg, 65%). 1H NMR (CDCb) d 7.25 (m, 5H), 5.10 (d, J = 14Hz, 1H), 4.23 (m, 1H), 4.08 (m, 1H), 3.85 (m, 1H), 3.72 (m, 1H ), 3.69 (s, 3H), 3.40 (m, 1H), 2.75 (m, 1H), 2.33 (m, 1H), 2.15 (m, 1H), 1.98 (s, 3H), 1.42 (s, 9H) , 1.20-1.40 (m, 7H), 0.83 (m, 6H) MS (M + H) * = 475. 2D (±) - (2R.3R.5R.1, S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxycarbonyl-pyrrole-5-ca-carboxylic acid t-butyl ester. A mixture of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-methoxycarbonyl-pyrrolidin-5 was heated. carboxylic (14 mg, 0.03 mmol) and ammonium formate (0.3 g) in ethanol (1.5 mL) with a catalytic amount of 10% palladium on activated carbon at about 75 ° C, for 1 hour. After filtering to remove the catalyst, the solvent was removed in vacuo. The residue was purified by chromatography on silica gel to give the compound of the title as a colorless oil (yield: 85 mg, 73%). MS (M + H) * = 385. 2E. Acid chlorohydrate (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-etiPpentyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid) A solution of t-butyl ester of the acid was sed (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid (8.5 mg, 0.022 mmol) in 4 N HCl in dioxane (1 mL) at room temperature for 24 hours. The solvent was removed in vacuo to give the title compound as an off-white solid. (yield 8 mg, 100%). 1H NMR (d6-DMSO) d 8.02 (d, J = 14Hz, 1H), 4.40 (m, 1H), 4.22 (m, 1H), 3.85 (t, J = 13Hz, 1H), 3.70 (, 1H), 365 (s, 3H), 3.15 (m, 1H), 2. 55 (m, 1H), 2.20 (m, 1H), 1.84 (s, 3H), 1.12-1.42 (m, 7H), 0.82 (t, J = 12.5Hz, 3H), 0.68 (t, 3H) MS (M + H) + = 329, (M-H) - = 327 Example 3 (±) - (2R, 3R, 5R.1'S) -2- (1-Acetamido-3-ethyl) Pent? L-3-cyano-pyrrolidin-5-carboxylic acid hydrochloride. 3A. acid t-butyl ester (±) - (2R.3R, 5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (hydroxyiminoformyl) -pyrrolidin-5 -carboxylic The title compound was prepared by reacting a solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-t-butyl ester. formyl-pyrrolidine-5-carboxylic hydroxylamine hydrochloride and aqueous solution of 10% potassium carbonate in methanol according to the procedure described by Chelucci et al., Tetrahedron: Asymmetry 5: 1973 (1994). 3B. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid. The title compound was prepared by reacting a solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-t-butyl ester. (hydroxyiminoformil) -pyrrolidine-5-carboxylic acid with 1,1 '-carbonyldiimidazole in dichloromethane according to the procedure described by Chelucci et al., Tetrahedron: Asymmetry 5: 1973 (1994). 3C. (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 1J, using (+) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid (t) butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) 3-et? L) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid. 3d Acid chlorhydrate (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 1K, using (+) - (2R, 3R, 5R, 1'S) -2-t-butyl ester (1-acetamido-3) -et? l) pentyl-3-cyano-pyrrolidin-5- carboxylic acid instead of (±) - (2R, 3R, 5R, 1 'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methox? methyl) -p? rrolidin t-butyl ester -5-carboxylic acid.

Example 4 - (±) (2R, 3R, 5R.1'S,) - 2- (1-Acetamido-3-ethyl) pentyl-3-propionyl-pyrrolidine-5-carboxylic acid hydrochloride. 4A. t-butyl ester of (+) - (2R, 3R, 5R, 1'S, 1"R) - and (± - (2R, 3R, 5 R.I'S.1" SI- 1 -Benci l-2- ( 1-acetamido-3-ethyl) pen ti l-3- (1-hydroxy) propi I-pyrrolidine-5-carboxylic acid ethyl magnesium bromide (0.070mL, 3M in ether) was added to a solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid (18 mg, 0.041 mmol) in 3 mL of tetrahydrofuran The reaction mixture was kept at 0 ° C and stirred for 1 hour, the reaction was set with aqueous ammonium chloride solution and partitioned between ethyl acetate and water. The organic was dried over MgSO 4, filtered and concentrated to give the title product (crude yield: 20mg, 100%) MS (M + H) * = 475. 4B. t-butyl ester of (±) - (2R, 3R, 5R, 1'S.) - 1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-propionyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 2A, using (±) - (2R, 3R, 5R, 1'S, 1"R) - and t-butyl ester of the acid (±) - (2R, 3R, 5R, 1 'S, 1"S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (1-hydroxy) propyl-pyrrolidine -5-carboxylic acid, 20 mg 0.041 mmol), instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-'acetamido-3-ethyl) t-butyl ester) pentyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid (yield: 11 mg, 56%). MS (M + H) * = 473. 4C. (±) - (2R.3R.5R.1'S.) - 2- (1-Acetamido-3-ethyl) -pentyl-3-propionyl-pyrrolidin-5-carboxylic acid t-butyl ester. A mixture of (±) - (2R, 3R, 5R, 1'S,) - 1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-prop, t-butyl ester was heated to 70 ° C. Onyl-pyrrole? Din-5-carboxylic acid (11 mg, 0.023 mmol), ammonium formate (250 mg) and palladium (15 mg, 10% on carbon) in ethanol (1 5 mL) during minutes The reaction was filtered, to remove the catalyst and concentrated. The residue was purified by chromatography on silica gel using 5% methanol / chloroform to give the title compound (yield: 8.5 mg, 95%).

MS (M + H) * = 383. 4D. (± (2R, 3R, 5R, 1'S,) - 2- (1-Acetamido-3-ethyl) pentyl-3-propionyl-pyrrolidine-5-carboxylic acid hydrochloride. acid (±) - (2R, 3R, 5R, 1, S,) - 2- (1-acetamido-3-ethyl) pentyl-3-propionyl-pyrrolidine-5-carboxylic acid (8 mg) was dissolved in 4 N HCl in dioxane (1 L) and it was stirred at room temperature for 24 hours. The reaction was concentrated in vacuo to give the title compound as an off-white solid (yield: 8 mg, 100%). H NMR (DMSO-dβ) D 8.03 (d, J = 14Hz, 1H), 4.41 (m, 1H), 4.20 (m, 1H), 3.92 (m, 1H), 3.68 (m, 1H), 3.46 (m , 1H), 2.65 (m, 2H), 2.00 (m, 1H) 1.84 (s, 3H), 1.10-1.35 (m, 9H), 0.95 (t, J = Hz, 3H), 0.81 (t, J = 12.5Hz, 3H), 0.75 (t, J = 12.5Hz, 3H) MS: (MH) - = 325, (M + 35) * = 361, (2M-H) "= 651; (M + H) + = 327, (2M + 1) * = 653, (2M + Na) * = 675.

Example 5 - (±) (2R, 3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl 3- (N-methylcarbamoyl) pyrrolidin-5-carboxylic acid hydrochloride. 5A. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-etl) pentyl-3- (N-methylcarbamoyl) pyrrolidin-5-carboxylic acid.

A solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid t-butyl ester ( 0.175 mmol) and triethylamine (18 mg, 0.175 mmol) in 10 mL THF was cooled in an ice bath. Isobutylchloroformate (24 mg, 0.175 mmol) was added and stirred for 30 min. Then methylamine (2.0 M in THF, 0.35 mL, 0.70 mmol) was added. The mixture was stirred while allowing to take room temperature overnight. The reaction was then diluted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% methanol / methylene chloride to give the title compound, as an oil (yield: 17.2 mg, 21%). MS: (M + H) * = 474 5B. t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-methylcarbamoyl) pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3- (N-methyl-carbamoyl) pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2-t-butyl ester (1-acetamido-3-ethyl) pentyl-3-methoxy-methyl-pyrrolidine-5-carboxylic acid (yield: 13 mg, 94%). MS: (M + H) * = 384 5C. f-Hydrochloride (2R, 3R, 5R.1'S) -2- (1-Acetamido-3-ethynyl-3- (N-methylcarbamoyl) oi rrol i din-5-carboxylic acid) The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-t-butyl ester - (N-methylcarbamoyl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-butyl ester (methox? methyl) -pyrrolidin- -carboxylic acid H NMR (D20): 5 4.43 (t, J = 10Hz, 1H), 4.36 (m, 1H), 4.09 (dd, 1H), 3. 08 (q, J = 10Hz, 1H), 2.75 (m, 4H), 2.25 (, 4H), 2.02 (s, 3H), 1.5- 1 15 (br, 7H), 0.80 (m, 6H). MS: (M + H) * = 328.

Example 6 (±) - (2R, 3R.5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-aminocarbamoyl) -p -rrolidin-5-carboxylic acid hydrochloride.

B 6A. t-butyl ester of acid (± 1- (2R.3R.5R.1'S -1-Benzyl-2- (1-a-tam-3-ethyl) pentyl-3- (N- (t-butoxycarbonaminocabamoyl) pyrrolidine-5-carboxylic acid A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1 'S) -1-benzyl-2- (1-acetamido) was stirred at room temperature for 6 hours. -3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid (60 mg, 0.13 mmol), t-butyl carbazate (21 mg, 0.16 mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride ( EDC, 31 mg, 0.16 mmol) and 1-hydroxybenzotriazole (9 mg, 0.065 mmol) in 3 mL of anhydrous THF The reaction was then diluted with ethyl acetate.The organic layer was washed with water and brine, dried over MgSO4, it leaked and it concentrated in vacuo The residue was purified by chromatography on silica gel using 2% methanol / methylene chloride to give the title compound, as an oil (yield 456 mg, 61%). MS: (M + H) * = 575 6B. acid t-butyl ester (±) - (2R.3R.5R, 1'S) -2- (1-Acetamido-3-et? l) pent? l-3- (N- (t-butoxycarbonyl) aminocarbamoyl) ) pyrrole din-5-carboxylic acid The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) t-butyl ester. benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (N- (t-butoxycarbonyl) aminocarbamoyl) pyrrolidine-5-carboxyl? co in place of the t-butyl ester of (+) - ( 2R, 3R, 5R, 1'S)) - 1-benzyl-2- (1-acetamido-3-ethyl) - entyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 28 mg, 75%) MS: (M + H) * = 484 . «- ::. p- .. 6C. (±) - (2R.3R.5R.1'S -2- (1-Acetamido-3-ethyl) pentyl-3- (N-aminocarbamoippyrrolidine-5-carboxylic acid hydrochloride) The title compound was prepared in accordance with method that is described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (N- (t-butoxy-carbonyl) aminocarbamo) t-butyl ester ) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine) t-butyl ester -5-carboxylic acid. 1H NMR (D20): d 4.32 (m, 2H), 4.18 (dd, 1H), 3.14 (q, J = 8.4Hz, 1H), 2.75 (m, 1H), 2.26 (m, 1H), 2.01 (s) , 3H), 1.50-1.15 (m, 7H), 0.80 (q, J = 7.5Hz, 6H) MS: (M + H) * = 329 Example 7 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-ethoxycarbonyl-pyrrolidin-5-carboxylic acid hydrochloride. 7A. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-ethoxycarbonyl-pyrrolidine-5-carboxylic acid . A solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid t-butyl ester (42 mg, 0.091 mmol), ethanol (0.5 mL), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC, 36 mg, 0.188 mmol) and 1-hydroxybenzotriazole (7 mg, 0.05 mmol) in 2 mL The anhydrous THF was stirred at room temperature overnight. The reaction was then diluted with ethyl acetate. The organic layer was washed with water, and brine, dried over gS? , it was filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 2% methanol / methylene chloride to give the title compound, as an oil (yield: 36 mg, 33%). 1 H NMR (CDCl 3): d 7.50-7.20 (br, 5H), 5.12 (d, J = 9Hz, 1H), 4.60-4.30 (br, 2H), 4.14 (q, J = 6Hz, 2H), 4.08 (, 1H), 3.85 (br, 1H), 3.72 (m, 1H), 3.40 (m, 1H), 2.75 (m, 1H), 2.32 (m, 1H), 1.97 (s, 3H), 1.40 (s, 9H) ), 1.37 (t, J = 6Hz, 3H), 1 20-1.50 (m, 7H), 0.83 (m, 6H).

Mass spectrography (M + H) * = 489 7B. (±) - (2R.3R.5R.1'S -2- (1-Acetamido-3-ethyl) pentyl-3-ethoxycarbonyl-pyrrolidin-5-carboxylic acid t-butyl ester.The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl t-butyl ester -3-ethoxy-carbon? L-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3, 5R, 1'S) -1-benzyl-2- (1-acetamido-3) -butyl ester ethyl) pentyl-3-methoxy-methyl-pyrrolidine-5-carboxylic mass spectrography: (M + H) * = 399. 7C. (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-etl) pentyl-3-ethoxycarbonyl-pyrrolidine-5-carboxylic acid hydrochloride. The title compound was prepared according to the method described in Example 2E, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-et) t-butyl ester ? l) pentyl-3-ethoxycarbonyl- pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-methoxycarbonyl-? irrolidin-5-butyl ester carboxylic 1H NMR (D20): 5 4.35 (m, 1H), 4.20 (q, J = 7.5Hz, 2H), 3.87-3.55 (m, 2H), 3.20 (q, J = 7.5Hz, 1H), 2.67 (m , 1H), 2.42 (m, 1H), 2.02 (s, 3H), 1.24 (t, J = 7.5Hz, 3H), 1.54-1.15 (m, 7H), 0.82 (m, 6 H). Mass spectrography: (M + H) * = 343, (M-H) "= 341.

EXAMPLE 8 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-acetyl-pyrro lidin-5-carboxylic acid hydrochloride. 8A. acid t-butyl ester (±) - (2R.3R.5R.1'S.1 * R) - v (±) - (2R.3R. 5R.1'S.1"S) -1-Benzyl-2- ( 1-acetamido-3-ethyl) pentyl-3- (1-hydroxy) ethyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 4A but using methyl bromide magnesium instead of ethyl magnesium bromide. 8B t-butyl ester of the acid (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-a ceta mido-3-ethyl) peptil-3-a ce til -pirrolidin-5- carboxylic The title compound was prepared according to the method described in Example 2A, using (±) - (2R, 3R, 5R, 1'S, 1"R) - and (±) - (t) butyl ester ( 2R, 3R, 5R, 1'S, 1"S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (1-hydroxy) ethyl-pyrrolidine-5-carboxylic acid, prepared in accordance with procedure described in Example 8A, in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-hydroxymethyl t-butyl ester -pyrrolidine-5-carboxylic acid. 1 H NMR (CDCl 3) d 5.00 (d, J = 9.7 Hz, 1 H), 3.94 (m, 2 H), 3.68 (m, 1 H), 3.55 (m, 1 H), 2.64 (m, 1 H), 2 32 (m , 1H), 2.29 (s, 3H), 2.20 (m, 1H), 1.94 (s, 3H), 1.43 (s, 9H), 1.15-11.35 (m, 7H), 080 (m, 6H). MS: (M + H) * = 459 8C. acid t-butyl ester (±) - (2R.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-acetyl-pyrrolidine-5-carboxyl? co. The title compound was prepared according to the method which is described in Example 4C, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-acetyl- t-butyl ester pyrrolidine-5-carboxylic acid, prepared according to the procedure described in Example 8B, in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-) t-butyl ester acetamido-3-ethyl) pentyl-3-propionylpyrrolidone-5-carboxylic acid. MS: (M + H) * = 369 8D. acid hydrochloride (±) - (2R.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-a -acetyl -pyr rolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) t-butyl ester ) pentyl-3-acetyl-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (t-butyl ester) methoxymethyl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-d 6) D 8.20 (m, 1 H), 4.35 (m, 1 H), 4.15 (m, 1 H), 4.03 (m, 1 H), 2.43 (m, 1 H), 2.03 (m, 1 H), 1.91 (s, 3H), 1.77 (s, 3H), 1.55 (m, 1H), 1.46 (m, 1H), 1.35 (m, 2H), 1.12 (m, 4H), 0.84 (m, 3H), 0.79 (m, 3H) MS: (M + H) * = 314, (MH) "= 312 »A7 .. J Example 9 Acid dichlorhydrate (+) - (2S.3R .5R.1 'S) -2- (1-Acetamido-3-et? L) pent? L-3-am? No-p? Rrol ? ? n-5-carbox? l? co 9A (±) - (2S.3R.5R) - and (±) - (2S.3S.5R) -1-benzyl-2-v? N? L-3-carboxy acid t-butyl ester lp? rrol? d? n-5-carboxyl? co A solution of t-butyl ester of (±) - (2S, 3R, 5R) - y (±) - (2S, 3S, 5R) -1 is prepared. -benzyl-2-v? n? l-3-form? lp? rrol? d? n-5-carboxylic acid (10 g, 31 7 mmol) (8 1 ratio), in 39 mL of ethanol The solution was treated with a suspension of silver oxide (83.8 g, 38 mmol) and potassium hydroxide (10 86 g, 194 mmol) in 65 mL of water. The reaction was stirred at room temperature for 1 hour and filtered through a pad of Celite * The ethanol was removed in vacuo The aqueous solution was acidified with acetic acid at approximately pH 4 The acidic solution was extracted with ethyl acetate The organic layer was washed with brine, dried over Na 2 SO 4, filtered and concentrated to give the title compound as brown oil (crude yield 8 2 g, 77%) The crude acid was used in the next step without further purification MS (M + H) * = 332, (M-H) = 330 9B. (±) - (2S, 3R.5R) -1-Benzyl-2-vinyl-3-benzyloxycarbonyl ester (I), n-5-ca-carboxylic acid amyl ester. A mixture of (±) - (2S, 3R, 5R) - and t-butyl ester of (±) - (2S, 3S, 5R) -1-benzyl acid (t) butyl ester was refluxed for 16 hours. L-2-vinyl-3-carboxyl-pyrrolidine-5-carboxylic acid (1.0 g, 3.02 mmol), diphenylphosphoryl azide (0.83 g, 3.32 mmol), benzyl alcohol (0.36 g, 4.53 mmol) and triethylamine (0.32 g, 3.32 g) mmol) in 30 mL of toluene. The solvent was evaporated and the residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 0.86 g, 65%). 1 H NMR (CDCl 3) d 7.20-7.40 (m, 10 H), 5.70 (m, 2 H), 5.10-5.23 (m, 3 H), 4.10 (m, 1 H), 3.85 (m, 1 H), 3.62 (m, 1 H) ), 3.45 (m, 2H), 2.50 (m, 1H), 1.70 (m, 1H), 1.41 (s, 9H). MS (M + H) * = 437. 9C. (±) - (2R.3R.5R) -1-Benzyl-2-formyl-3-benzyloxycarbonylamino-pyridine-5-carboxylic acid t-butyl ester. Osmium tetroxide (3 crystals) was added to a solution stirring of the (±) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3-benzyloxycarbonylamino-pyrrolidin-5-carboxylic acid ester (1.10 g, 2.52 mmol), N -methylmorpholine N-oxide (0.95 g, 8.07 mmol), in 27 mL of acetone / water (8: 1), was kept at room temperature. After 6 hours, 10% aqueous solution of Na 2 S 2 γ 3 was added and stirring continued for an additional 15 minutes. The reaction was extracted with dichloromethane and the organic layer was concentrated to give the crude diol intermediate. The diol product was used in the next step without further purification. MS (M + H) * = 471. Sodium periodate (1.0 g, 4.52 mmol) was added in portions to a stirred solution of the crude diol (-1.25 g, 2.66 mmol) in 21 mL of THF / water (6: 1). ). The reaction was stirred for 1 hour and then diluted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel using 15% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 0.66 g, 60%). 1 H NMR (CDCl 3) 5 9.44 (d, J = 1.2 Hz, 1 H), 7.20-7.40 (m, 10 H), 5.98 (d, J = 14 Hz, 1 H), 5.10 (m, 2 H), 4.45 (m, 1 H) ), 3.90 (m, 2H), 3.70 (m, 1H), 3.60 (m, 1H), 2.43 (m, 1H), 1.70 (m, 1H), 1.45 (s, 9H), MS (M + H) * = 439 9D. t-butyl ester of (+) - (2R.3R.5R.1 'R) - and t-butyl ester of (±) - (2R, 3, 5R, 1'S) -1-Benzyl-2- ( 1-hydroxy-3-ethyl) pentyl-3-benzyloxycarbon? Lamino-pyrrolidine-5-carboxyl? Co. 1-Bromo-2-ethylbutane (1.7 g, 10.3 mmol) was added to a solution of dibromoethane (3 drops) in 15 mL of dry THF, under argon, in a container charged with magnesium (0.25 g, 10.3 mmol). The reaction mixture was heated to reflux for 45 minutes, until most of the magnesium reacted. The solution was allowed to cool to room temperature and transferred by means of a cannula to a suspension of CuBr SMe2 (2.12 g, 10.3 mmol) in 15 mL of dry THF, kept under argon, at -10 ° C. The mixture was stirred for 0.5 hour until the solution darkened. A solution of (±) - (2R, 3R, 5R) -1-benzyl-2-formyl-3-benzyloxycarbonyl-5-pyrrolidin-5-carboxylic acid t-butyl ester (0.45) was added dropwise. g, 1.03 mmol) in 10 mL of THF and stirred for 1.5 hours, while maintaining the temperature at 0 ° C. The reaction was set with aqueous ammonium chloride solution, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give alcoholic adducts as a pale yellow oil (yield: 160 mg, 30%). 1 H NMR (CDCl 3) d 7.20-7.40 (m, 10 H), 6.10 (d, J = 14 Hz, 1 H), 5.10 (m, 2 H), 4.22 (m, 1 H), 4.01 (m, 1 H), 3.71 (m , 1H), 3.65 (m, 2H), 3.55 (m, 1H), 3.20 (m, 1H), 2.00-2.30 (m, 2H), 1.45 (s, 9H), 1.15-1.40 (m, 7H), 0.84 (m, 6H) MS (M + H) * = 525 9E. (±) - (2R.3R.5R) -1-Benzyl-2- (1-oxo-3-ethyl) pentyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid t-butyl ester. A solution of oxalyl chloride (0.29 ml, 2 M in CH 2 Cl 2) in 5 L of dry dichloromethane was prepared and kept under a nitrogen atmosphere at -78 ° C. DMSO (90 mg, 1.14 mmol) was added to the solution. The mixture was stirred for 15 minutes. The alcohol adduct, prepared above, (150 mg, 0.286 mmol), in 5 mL of dichloromethane, was added dropwise to the cold reaction mixture (-78 ° C). The solution was stirred, at -78 ° C, for 1 hour. Triethylamine (250 mg, 2.29 mmol) was added slowly. The reaction was allowed to come slowly to room temperature and then diluted with dichloromethane. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel using 5% ethyl acetate / hexanes to give the title compound (yield: 100 mg, 67%). H NMR (CDCl 3) d7.35 (m, 10H), 5.10 (m, 2H), 4.28 (m, 1H), 395 (m, 2H), 2.60 (m, 1H), 2.40 (m, 1H), 2.03 (m, 1H), 1.70 (m, 2H), 1.45 (s, 9H), 1.10-1.30 (m, 7H), 0.70 (m, 6H) MS (M + H) * = 523. 9F. acid t-butyl ester (±) - (2S.3R, 5R.1'R) - v t-butyl ester of (±) - (2S, 3R, 5R, 1'S) -1-Benzyl-2- ( 1-amino-3-ethyl) pentyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid. A mixture of (±) - (2R, 3R, 5R) -1-benzyl-2- (1-oxo-3-ethyl) pentyl-3-benzyloxycarbonylamino-pyrrolidine acid t-butyl ester was refluxed for 18 hours. -5-carboxylic acid (90 mg, 0.172 mmol), ammonium acetate (400 mg, 5.17 mmol) and sodium cyanoborohydride (65 mg, 1.03 mmol) in 5 mL in methanol. Additional portions of ammonium acetate and sodium cyanoborohydride were added and heating continued for 2 more hours. The reaction was set with 1N sodium hydroxide, and diluted with dichloromethane. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel using ethyl acetate / hexanes 1: 1 followed by 5% methanol / dichloromethane to give the title compounds, (yield: 58 mg, 64%) MS (M + H) * = 524 - ^ 1-l-ÍÍM-fin ^ ÜU 9G acid t-butyl ester (±) - (2S, 3R, 5R, 1'R) - v t-butyl ester of (±) - (2S.3R, 5R, 1'S) -1-Benzyl-2- ( 1-acetamido-3-ethyl) pentyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid. A solution of t-butyl ester of (±) - (2S) acid was stirred for 1 hour at room temperature., 3R, 5R, 1'R) - and t-butyl ester of (+) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-ethyl) pentyl-3-acid benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid (50 mg, 0.096 mmol) and acetic anhydride (117 mg, 1.15 mmol) in 5 mL of dichloromethane. The solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel using 30-50% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 51 mg, 97%). H NMR (CDCl 3) 5 7.72-7.35 (m, 10H), 5.82 (d, J = 14Hz, 1H), 5.10 (m, 2H), 4.38 (m, 1H), 4.15 (m, 2H), 3.63 (m , 1H), 3.38 (m, 1H), 3.10 (m, 1H), 2.15 (m, 1H), 2.00 (s, 3H), 1.65 (m, 1H), 1.42 (s, 9H), 1.20-1.35 ( m, 7H), 0.80 (m, 6H) MS (M + H) * = 567. 1 9H. t-butyl ester of f ±) - (2S.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-amino-pyrrolidine-5-carboxylic acid. A solution of (±) - (2S, 3R, 5R, 1'R) - and t-butyl ester of (±) - (2S, 3R, t-butyl ester, was heated at 80 ° C for 45 minutes. 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid (49 mg, 0.087 mmol), ammonium formate (150 mg, 0.22 mmol) and 10% palladium on activated carbon in ethanol (5 mL). After filtering to remove the catalyst, the solvent was removed. The residue was purified by silica gel chromatography using 5-10% methanol / dichloromethane to give the diastereomers, (±) - (2S, 3R, 5R, 1'S) t-butyl ester (19 mg) and t-butyl (±) - (2S, 3R, 5R, 1'R) acid ester (8.6 mg) of 2- (1-acetamido-3-ethyl) pentyl-3-amino-pyrrolidine-5-carboxylic acid. H NMR (CDCl 3) d 6.00 (d, J = 14Hz, 1H), 3.90 (m, 1H), 3.73 (m, 1H), 3.49 (m, 1H), 3.10 (m, 1H), 2.48 (m, 1H) ), 2.03 (s, 3H), 1.82 (m, 1H), 1.48 (s, 9H), 1.15-1.42 (m, 7H), 0.85 (m, 6H) MS (M + H) * = 342. 91. (+) - (2S, 3R, 5R, 1 'S) -2- (1-Acetamido-3-ethyl) pentyl-3-amino-pyrrolidine-5-carboxylic acid dihydrochloride. A solution of t-butyl ester of (±) - (2S, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-amino-pyrrolidinone was stirred at room temperature for 3 hours. 5-carboxylic acid (17 mg, 0.050 mmol) in 1 mL of 6 N HCl. The solvent was removed under high vacuum to give the title compound as a white solid (yield: 15 mg, 100%) 1H NMR (d6-DMSO) 5 8.28 (bs, 1H), 7.90 (d, J = Hz, 1H), 4.71 (d, J = 14Hz, 1H), 4.39 (m, 1H), 4.10 (m, 1H), 3.92 (m, 1H), 3.08 (m, 1H), 2. 64 (m, 1H), 2.31 (m, 1H), 1.95 (m, 1H), 1.88 (s, 3H), 1 50 (m, 1H), 1. 10-1.40 (m, 7H), 0.72-0.90 (m, 6H) MS (M + H) * = 286.

Example 10 (±) - (2S, 3R, 5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-acetamido-pyrrole-din-5-carboxylic acid hydrochloride. 10A. acid t-butyl ester (±) - (2S.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-amino-pyrrolidine-5-carboxylic acid. A solution of t-butyl ester of (+) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-etl) pentyl-3-benzyloxycarbonylamino-pyrrolidin-5 carboxylic acid (50 mg, 0.88 mmol) was stirred with 10% palladium on carbon (5 mg) in 50 mL of ethyl acetate under 1 atmosphere of hydrogen for 45 minutes. The reaction was filtered and concentrated to give the title compound as an oil (crude yield: 35 mg, 92%). MS (M + H) * = 431. 10B. acid t-butyl ester (±) - (2S.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-acetamido-pyrrolidine-5-carboxylic acid. A solution of t-butyl ester of the acid (±) - was reacted ^^^^^ (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-amino-pyrrolidone-5-carboxylic acid (35 mg, 0.080 mmol) with acetic anhydride (0.05 mL) in 8 mL of dichloromethane for 1 hour. The reaction was concentrated and the residue was purified by chromatography on silica gel 5 using 50% ethyl acetate / hexanes followed d? 3% methanol / dichloromethane to give the title compound (yield: 30 mg, 80%). 1 H NMR (CDCl 3) 57.20-7.35 (m, 5 H), 6.62 (d, J = 14 Hz, 1 H), 5.34 (d, J = 14 Hz, 1 H), 4.42 (m, 2 H), 4.20 (m, 1 H), 3.68 (m, 1H), 3.42 (m, 1H), 10 3.10 (m, 1H), 2.18 (m, 2H), 2.02 (s, 3H), 1.96 (s, 3H), 1.45 (s, 9H), 1.25-1.42 (m, 7H), 0.85 (m, 6H). MS (M + H) * = 474. 10C. (±) - (2S, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-acetamido-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example U, using (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester. -3-ethyl) pentyl-3-acetamido-20-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) -butyl ester 3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid. The residue was purified by chromatography on silica gel using 5% methanol / dichloromethane to give the compound title (yield: 11 5 mg, 50%) 1 H NMR (CDCl 3) d 6.20 (d, J = 14 Hz, 1 H), 594 (d, J = 14 Hz, 1 H), 4.24 (m, 1H), 4.08 (m, 1H), 3.95 (m, 1H), 3.75 (m, 1H), 3 18 (m, 1H), 2.45 (m, 1H), 2.02 (s, 3H), 1.96 (s, 3H), 1.82 (m, 1H), 1.49 (s, 9H), 1.20-1.42 (m, 7H), 085 (m, 6H). MS (M + H) * = 384. 10D (±) - (2S.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-acetamido-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared in accordance with method described in Example 1K, using (±) - (2S, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-acetamido tert-butyl ester -pyridine-5-carboxylic acid (11.0 mg, 0.029 mmol) in place of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pent acid t-butyl ester L-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid (yield: 11.0 mg, 100%). 1H NMR (d6-DMSO) 5 8.15 (d, J = 14Hz, 1H), 8.05 (d, J = 14Hz, 1H), 4.35 (m, 1H), 4.28 (m, 1H), 4.19 (m, 1H) , 3.59 (m, 1H), 1.90 (s, 3H), 1.81 (s, 3H), 1.15-1.40 (m, 7H), 0.80 (m, 6H). MS: (M-H) "= 326, (M + 35) * = 362; (M + H) * = 328, (M + 23) * = 350 gfa ^ Example 11 (±) - (2S.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxycarbonylamino-pyrrolidine-5-carboxylic acid hydrochloride. 11A. acid t-butyl ester (± - (2S.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-methoxycarbonylamino-pyrrolidine-5-carboxylic acid. (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) penti-3-amino-pyrrolidin-5-t-butyl ester solution carboxylic acid with methyl chloroformate and triethylamine in dichloromethane The reaction was partitioned between dichloromethane and water.The organic layer was concentrated to give the title compound. 11B. t-butyl ester of the acid +) - (2S.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxycarbonylamino-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 1J, using acid t-butyl ester (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-aceta-do-3-ethyl) pentyl-3-methoxycarbonylaminopyrrolidine-5-carboxylic acid instead of t-butyl ester of the (±) - (2R, 3R, 5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid. 11C. (±) - (2S.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxycarbonylamino-pyrrolidine-5-carboxylic acid hydrochloride. The title compound was prepared according to the method described in Example 1K, using (±) - (2S, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) t-butyl ester ) pentyl-3-methoxycarbonylamino-pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid.

Example 12 (±) - (2 R 3 R 5 R 1 S) -2-f 1-Acetamido-3-ethyl-pentyl-3 - (α-midazol-4-yl) -5-carboxylic acid dichloride. 12A. acid t-butyl ester (±) - (2R.3R .5R.1 'S) -1-Benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-diazoacetyl-5-carboxylic acid. A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1 'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-carboxylic acid was reacted. pyrrolidine-5-carboxylic acid (405.3 mg, 0.88 mmol) and N-methylmorpholine (106 ni, 0.96 mmol) in TH F (20 ml) with isobutyl chloroformate (96 D i, 0.93 mmol) at -10 ° C for 30 minutes. A distilled solution of diazomethane solution in ether prepared from the reaction of diazald (2.4 g) in ether (60 ml) with a solution of potassium hydroxide (2.4 g) in ethanol was introduced into the reaction vessel with a cannula. 15 ml) and water (15 ml). The reaction was stirred for 3 hours at room temperature then diluted with ether. The organic layer was washed with brine, dried (Na2SO4) and concentrated to give the title compound as a thick oil (430.4 mg). 12B (±) - (2R.3R .5R.1 'S) -1-Benzyl-2- (1-Acetamido-3-ethyl) pentyl-3-bromoacetyl-5-carboxylic acid t-butyl ester. A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1 'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-diazoacetyl-5 was reacted carboxylic acid (427.4 mg, 0.88 mmol) in dioxane (50 ml) with hydrobromic acid (0.25 ml, 2.2 mmol) at 0 ° C for 0.5 hours. The reaction was set with saturated aqueous sodium bicarbonate solution (25 ml) and concentrated in vacuo. The residual aqueous layer was extracted with dichloromethane (3x50 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using methanol in 5% dichloromethane to give the title compound as a white foamy solid (379.3 mg, 80.2%). MS: (M + H) * = 539. 12C. acid t-butyl ester (±) - (2R.3R.5R.1 'S) -1-Benzyl-2- (1 -acetamido-3-ethyl) pentyl-3- (imidazol-4-yl) -5 -carboxylic (±) - (2R, 3R, 5R, 1 'S) -1-benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-bromoacetyl-5-carboxylic acid t-butyl ester (60) mg, 0.1 12 mmol) with formamidine acetate (120 mg, 1.15 mmol) in liquid ammonia and heated at 45 ° C in a sealed tube for 20 h. The reaction was concentrated in vacuo. The residue was treated with aqueous NaHCO 3 solution and extracted with dichloromethane (5 × 20 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using 5% methanol in dichloromethane to give the title compound as a white solid (21.2 mg, 39.4%). MS: (M + H) * = 483. . gljÜ ^^^^^. 12D. t-butyl ester of (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-4-yl) -5-carboxylic acid. The title compound was prepared according to the method described in Example U, using (±) - (2, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester. -3-ethyl) pentyl-3- (imidazol-4-yl) -5-carboxylic acid in place of the (±) - (2 R, 3 R, 5R, 1'S) t-butyl ester) -1-benzyl- 2- (1-Acetamido-3-ethyl) pentyl-3-methoxy-methyl-1-pyrrolidine-5-carboxylic acid (yield: 12.9 mg, 66.2%). 1 H NMR (CDCl 3): Q 0.75-0.81 (m, 6H), 1.17 - 1.42 (m, 7H), 1.47 (s, 9H), 2.03 (s, 3H), 2.66 (m, 1H), 3.50 (m, 1H), 3.73 (m, 1H), 3.86 (m, 1H), 4.06 (m, 1H), 7.04 (br s, 1H), 7.86 (br s, 1H). MS: (M + H) * = 393. 12E. (±) - (2R, 3R.5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-4-yl) -5-carboxylic acid dihydrochloride. The title compound was prepared according to the method described in Example 1K, using acid t-butyl ester (±) - (2R, 3R, 5, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (imidazol-4-yl) -5-carboxylic acid instead of t-butyl ester ( ±) - (2R, 3R, 5R, 1'S) -2- (1 -acetamido-3-ethyl) pentyl-3- (methoxymethi I) -pyrrolid i-5-carboxylic acid to give the solid title compound (yield: 12.0 mg, 96.0%). 1H NMR (DMSO-d6): 0.67 (t, J = 7 Hz, 3H), 0.75 (t, J = 7 Hz, 3H), 1.11 (m, 3H), 1.23 (m, 4H), 1.78 (s) , 3H), 2.33 (m, 1H), 2.70 (m, 1H), 3.69 (dt, 1H), 3.95 (dd, 1H), 4.29 (, 1H), 4.48 (dd, 1H), 7.63 (s, 1H) ), 8.28 (d, J = 9 Hz, 1H), 9.06 (s, 1H). MS: (M + H) * = 337.

Example 13 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (oxazol-2-yl) -pyrrolidine-5-carboxylic acid hydrochloride. 13A. acid t-butyl ester (± - (2R, 3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (N- (2-hydroxyethyl) carbamoypropyl ester id-5-carboxylic acid The title compound is prepared according to the method described in Example 5A, but using ethanolamine instead of N-methylamine hydrochloride 13B. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (oxazolin-2-yl) -pyrrolidin-5 -carboxylic A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (N- (2)) is reacted. -hydroxyethyl) carbamoyl) -pyrrolidine-5-carboxylic acid, triethylamine (4 eq.), carbon tetrachloride (3.5 eq.) in acetonitrile with triphenylphosphine (3.15 eq.) for 16 h at room temperature. The reaction was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, and brine, dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using ethyl acetate / hexanes to give the title compound. 13C. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-etl) pentyl-3- (oxazol-2-yl) -pyrrolidine -5-carboxylic acid. A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (oxazolin-2-) is reacted. il) - pyrrolidine-5-carboxylic acid with nickel peroxide in cyclohexane according to the method described by Meyer in J. Org. Chem. 1979, 497-501 to give the title compound. 13D. (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-et? ppentyl-3- (oxazol-2-yl) -pyrrolidine-5-carboxylic acid t-butyl ester. The title compound is prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-) t-butyl ester. 3-Ethyl) pentyl-3- (oxazol-2-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3, 5R, 1'S) -1-benzyl t-butyl ester -2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid. 13E. (±) - (2R.3R.5R.1 'S -2- (1-Acetamido-3-ethyl) pentyl-3- (oxazol-2-yl) -pyrrolidine-5-carboxylic acid dihydrochloride. The title is prepared according to the method described in Example 1K, using acid t-butyl ester (±) - (2R, 3R, 5R, 1 'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (oxazol-2? L) -pyrrole-din-5-carboxylic acid instead of acid t-butyl ester (±) - (2 R, 3 R, 5 R, 1 'S) -2- (1 -acetam? do-3-ethyl) pen ti l-3-methoxy meti l-pyrrolidi n -5-carboxylic acid.

Example 14 (±) - (2S.3R.5R.1 'S) -2- (1-Acetamido-3-methyl) butyl-3- (N-methylamino) pyrrolidine-5-carboxylic acidhydrochloride. 14 TO. (±) - (2S.3R.5R) -1-Benzyl-2-vinyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid t-butyl ester. A solution of (±) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3-benzyloxycarbonylaminopyrrolidine-5-carboxylic acid t-butyl ester (2.08 g, 4.77 mmol) was dissolved in 50 mL of DMF anhydrous and kept under a nitrogen atmosphere. The solution was treated with sodium hydride (0.32 g, 8 mmol), and stirred at room temperature for 30 minutes. The solution was treated with iodomethane (0.8 ml, 12.85 mmol) and stirred for an additional hour. The reaction was set with water and extracted with ethyl acetate. The combined organic layers were concentrated to give the crude product, which was then purified by chromatography on silica gel to give the title compound as an oil (yield: 1.75 g, 81%). 1 H NMR (CDCl 3) 5 7.36-7.20 (m, 10H), 5.75-5.50 (br, 1H), 5 25-5.07 (m, 4H), 4.75-450 (br, 1H), 3.97 (d, J = 13.5 Hz, 1H), 3.75 (m, 1H), 3.61 (d, J = 13.5Hz, 1H), 3.50 (m, 1H), 293 (s, 3H), 2.45 (m, 1H), 1.75 (m, 1H) ), 1.46 (s, 9H). MS (M + H) * = 451. 14B. t-butyl ester of (±) - (2R, 3R, 5R) -1-Benzyl-2-formyl-3- (N-methyl-N-benzyl oxycarbonyl my no) pyrrole n-5-carboxyl ico acid. The title compound was prepared according to the method described in Example 9C, using (±) - (2S, 3 R, 5 R) -1-benzyl-2-vi or l-t-butyl ester 3- (N-methyl-N-benzyl oxycarboni lami no) -pyrrolidine-5-carboxylic acid instead of (±) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3-t-butyl ester -benzene-loxycarbonylamino-pyrrolidine-5-carboxylic acid. (Yield: 747 mg, 42%.) MS (M + H) * = 453. 14C. acid t-butyl ester (±) - (2R.3R.5R) -1-Benzyl-2- (1-oxo-3-methyl) butyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidin-5- carboxylic Isobutyl magnesium chloride (2.0 M in ether, 0.68 ml) was added dropwise over approximately 12 minutes to a solution of t-butyl ester of (±) - (2R, 3R, 5R) -1-benzyl- 2-formyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid (196 mg, 0.43 mmol) in 5 mL of anhydrous THF was maintained at -78 ° C. The resulting yellow solution was stirred at -78 ° C for 1 hour. The solution was set with saturated aqueous solution of ammonium chloride, and extracted with ethyl acetate. The organic layer was concentrated and the crude product was oxidized according to the procedure described in Example 9D. Purification by column chromatography on silica gel, with 10-25% ethyl acetate / hexanes, gave the title compound (yield: 78 mg, 36%). 1 H NMR (CDCl 3) 5 7.46-7.25 (m, 10H), 5.09 (br, 2H), 4.90-4.60 (m, 1 H), 3.97-3.65 (m, 4H), 3.00 (s, 3H), 2.60 (br, 1 H), 2.20-1.80 (m, 3H), 1.46 (s, 9H), 0.80-0.67 (m, 7H). MS (M + H) * = 509. 14D. t-butyl ester of (+) - (2S, 3R.5R.1'R) - and t-butyl ester of (±) - (2S, 3R, 5, 1'SM-Benzyl-2- (1 amino-3-methyl) butyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 9F, using t-butyl ester of (±) - (2R, 3R, 5R) -1-benzyl-2- (1-oxo-3-methyl) butyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R) -1-Benzyl-2-formyl-3-benzyloxycarbonyl-amino-pyrrolidine-5-carboxylic acid t-butyl ester (Yield: 97 mg, 65%.) MS ( M + H) * = 510. 14E. acid t-butyl ester (±) - (2S.3R, 5R.1 'R ~ and t-butyl ester of the acid (±) - (2S.3R.5R.1'S) -1-Benzyl-2- (1 -acetamido-3-methyl) butyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid A solution of t-butyl ester of (±) - (2S, 3R, 5R) was reacted , 1'R) - and (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-methyl) butyl-3- (N-methyl-N-benzyloxycarbonylamino pyrrolidin-5-carboxylic acid (47) mg, 0.094 mmol) with acetic anhydride (0.15 mL) in 4 mL of dichloromethane at room temperature for 2 hours. The reaction was concentrated in vacuo to give the title compound. MS (M + H) * = 552. 14F. t-butyl ester of (+) - (2S.3R, 5R.1 'S) -2- (1-Acetamido-3-methyl) butyl-3- (N-methylamino) pyrrolidine-5-carboxylic acid. A solution of t-butyl ester of (±) - (2S, 3R, 5R, 1 'R) - and (±) - (2S, 3R, 5R, 1' S) -1 -benzyl-2- (1 -acetamido-3-methy1) butyl-3- (N-methyl-N-benzyloxycarbonylamino) pyrrolidine-5-carboxylic acid (0.094 mmol), palladium (40 mg, 10% in carbon) and ammonium formate (160 mg) in 3 mL of ethanol was heated to reflux for 30 minutes. More palladium on charcoal (15 mg) and ammonium formate (50 mg) was added. The solution was stirred for a further 15 minutes and the mixture was then filtered to remove solids and catalyst. The filtrate was evaporated and the residue was purified by chromatography on silica gel methanol / dichloromethane 5% and NH40H 1% to give t-butyl ester of (±) - (2S, 3R, 5R, 1 'S) acid ( 15.4 mg, lower Rf) and t-butyl ester of (±) - (2S, 3R, 5R, 1 'R) (5.4 mg, higher Rf) -2- (1 -acetamido-3-methyl) butyl-3 - (N-Methyl amino) pyrrolidine-5-carboxyelines (yield: . 8 mg, 68%). 14G. (+) - (2S, 3R.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (N-methylamino) pyrrolidine-5-carboxylic acid dihydrochloride. A solution of t-butyl ester of (±) - (2S, 3R, 5R, 1'S) -2- (1-Acetam-do-3- methyl I) butyl-3- (Nm eti lami no) pyrrolid n-5-carboxylic acid (9.4 mg) was stirred with 4N aqueous HCl solution (-1.5 mL) for 2 hours. The reaction was concentrated in vacuo to give the title compound (yield: 10 mg, 100%). 1 H NMR (major peaks) (DMSO-dβ) G2.57 (s, 3H), 1.90 (s, 3H), 1.47 (m, 3H), 0.91 (d, J = 7.5Hz, 3H), 0.83 (d, J = 7.5Hz, 3H) MS: (M + H) * = 272.

Example 15 (+) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid chloride. < and NH N = 15A. t-butyl ester of acid I (+ W2R, 3R, 5R, 1'S) -1-Benzyl-2-d-acetamido-3- -etiDpenti 1-3- (imidazol-2-iH-pyrroidi in-5 -carbo xylic .

Ammonia gas was injected slowly through a solution of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-t-butyl ester. -formyl-pyrrolidin-5-carboxylic acid (20 mg, 0045 mmol) and glyoxal (6.2 uL, 0.054 mmol, 1.2 equiv.) in 5 mL of methanol, 5 was maintained at 0 ° C, for 5 minutes. After 7 hours at 0 ° C, more glyoxal (10 uL) was added and ammonia was injected through the solution for 5 minutes. The reaction was allowed to stir at room temperature for 16 hours. A final aggregate of glyoxal (10 uL) and ammonia as described above, followed by The reaction at room temperature for an additional 4 hours produced a complete reaction. The reaction was concentrated in vacuo and purified by chromatography on silica gel using 50% ethyl acetate / hexanes, followed by 10% methanol / chloroform to give the title compound as a solid (yield: 19.9 mg, 91%). 1 H NMR (CDCl 3): d 0.67 (t, J = 7.2 Hz, 3 H), 0.73 (t, J = 7.2 Hz, 3 H), 1.09-1.32 (m, 7 H), 1.41 (s, 9 H), 2.00 (m , 1H), 2.09 (s, 3H), 2.79 (m, 1H), 3.29 (m, 1H), 3.66 (dd, J = 9.6, 2.7 Hz, 1H), 3.77 (m, 1H), 3.92 (d, J = 13.4 Hz, 1H), 4.04 (d, J = 13.4 Hz, 1H), 4.22 (dd, 1H), 4.49 (m, 20 1H), 6.08 (brs, 1H), 7.00 (s, 2H), 7.21-7.34 (m, 5H). MS (M + H) * = 483. 14 (r- "NH 15B. (±) - (2R, 3R, 5R, 1 'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid t-butyl ester A mixture of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (t) butyl ester was refluxed for 15 minutes. imidazol-2-yl) -pyrrolidin-5-carboxylic acid (17 mg, 0.035 mmol), ammonium formate (250 mg) and 10% palladium on carbon (20 mg), in 5 mL of ethanol, The reaction was concentrated under vacuum and the residue was purified by chromatography on silica gel using 5% methanol / dichloromethane and 0.25% ammonium hydroxide to give the title compound as a white solid (yield: 11.3mg, 81.9%). MS (M + H) * = 393. 15C. (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid dihydrochloride. The (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3 - (? Midazole-2?) -pyrrolene din was dissolved. -5-carboxyl? Co (11 mg, O 028 mmol) in 2 mL of 6N HCl and stirred at room temperature for 2 hours. The reaction was concentrated in vacuo to give the title compound, as an off-white solid. (yield 11.3 mg, 100%). H NMR (DMSO-d6): d 0.71 (t, J = 7 Hz, 3H), 0.75 (t, J = 7 Hz, 3H), 1 09-1.28 (m, 7H), 1.74 (s, 3H), 2.43 (m, 1H), 2.80 (m, 1H), 3.85 (m, 1H), 4.04 (m, 1H), 4.29 (m, 1H), 4.52 (m, 1H), 7.64 (s, 2H), 8.07 (br d, J = 9 Hz, 1H) MS (M + H) * = 337 and (MH) "= 335.

Example 16 (±) - (2R.3R, 5R.1 'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-dimethylcarbamoyl) pyrrolidine-5-carboxylic acid hydrochloride. 16A. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3? NN-dimethylcarbamoyl) pyrrolidin-5- carboxylic The title compound was prepared according to the method described in Example 5A but using N, N-dimethylamine instead of N-methylamine (yield - 10 mg, 23%) Mass spectrography: (M + H) * = 488 16B (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-methylcarbamoyl) pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3- (N, N-dimethylcarbamoyl) pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2-t-butyl ester (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid to give the title compound (yield: 5.5 mg, 67%). Mass spectrography: (M + H) * = 398. 16C. acid t-butyl ester (±) - (2R.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pe nt? l-3- (N. N-di met ilcarbamoyl) pyrrolid i n-5-carboxylic. The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) t-butyl ester ) pentyl-3- (N, N-dimethyl-carbamo? l) pyrrolidin-5-carboxyl? co instead of t-butyl ester of the acid (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid. 1H NMR (major peaks) (D20) d 3.15 (s, 3H), 2.94 (s, 3H), 1.98 (s, 3H), 0.80 (m, 6H) MS (M + H) * = 342, (MH) '= 340.

Example 17 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-Ethyl) pent? L-3-cyano-pyrrolidine-5-carboxylic acid hydrochloride. 17A. (±) (2S.3R.5R) -1-Benzyl-2-vinyl-3-cyano-pyrrolidine-5-carboxylic acid.

A solution of (±) - (2S, 3S, 5R) -1-benzyl-2-vinyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester (8: 1 ratio) (5g, 15.9 mmol) Hydroxylamine hydrochloride (1.28 g, 18.5 mmol) and 10% aqueous potassium carbonate solution (8 mL) in 20 mL of methanol, according to the procedure described by Chelucci ef a /., Tetrahedron: Asymmetry 5: 1973 ( 1994) gave the intermediate oxime product. The crude oxime, prepared above, was reacted with 1,1'-carbonyldiimidazole (3.9, 23.9 mmol) in 50 mL of dichloromethane for 3 hours, at room temperature. The reaction was concentrated in vacuo and chromatographed on silica gel with acetate ethyl acetate / hexanes 2-10% to give the title compound (yield: 2.5g, 50%) MS (M + H) * = 313 17B. (± - (2R.3R, 5R) -1-Benzyl-2-formyl-3-cyano-pyrrolidine-5-carboxylic acid t-butyl ester The title compound is prepared according to the method described in Example 1D, but using (±) (2S, 3R, 5R) -1-benzyl-2-vinyl-3-cyano-pyrrole-din-5-carboxylic acid instead of (±) - (-) - t-butyl ester 2S, 3R, 5R) -1-benzyl-2-v? Nl-3- (f-butylmethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid (yield: 2.2 g, 80%) .MS (M + H) * = 315 17C. acid (±) - (2R, 3R, 5R) -1-Benzyl-2- (1-oxo-3-ethyl) - entyl-3-cyano-pyrrolidine-5-carboxyl-co-t-butyl ester. The title compound was prepared according to the method described in Example 1E, but using (±) (2S, 3R, 5R) -1-benzyl-2-formyl-3-cyano-pyrrolidine-5-carboxylic acid in place of t-butyl ester % -B? NfM? - of (±) - (2, 3R, 5R) -1-benzyl-2-formyl-3- (f-butyldimethylsilyloxymethyl) -pyrrole-din-5-carboxylic acid (yield 04 g, 27% ) MS (M + H) * = 399 17D. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-amino-3-ethyl) pentyl-3-cyano-pyrrole-din-5-carboxylic acid. The title compound was prepared according to the method described in Example 1F, using (±) - (2R, 3R, 5R) -1-benzyl-2- (1-oxo-3) t-butyl ester -ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R) -1-benzyl- 2- (1-oxo-3-eti) t-butyl ester l) pentyl-3- (f-butyldimethylsilyl-1-yl) -pyrrolidin-5-carboxylic acid (yield 0.215 g, 50%). MS (M + H) * = 400 17E. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid. The title compound is prepared according to the method described in Example 1G, using acid t-butyl ester _ &-Batüü! l * -: (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid instead of t-butyl ester ( ±) - (2R, 3R, 5R, 1 'R) - and t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-ethyl) ) pentyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid (yield 0.210 g, 90%). 1 H NMR (CDCl 3) d 7.25 (m, 5 H), 5.08 (m, 1 H), 4.40 (m, 1 H), 4.15 (m, 1 H), 3.78 (m, 1 H), 3.48 (m, 1 H), 2.93 ( m, 1H), 2.32 (m, 1H), 2.12 (m, 1H), 2.02 (s, 3H), 1.52 (s, 9H), 1.35 (, 7H), 0.85 (m, 6H) MS: (M + H) * = 442. 17F. (±) - (2R, 3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) penti-3-cyano-pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (t) butyl ester ( 1-acetamido-3-ethyl) pentyl-3-methoxy ethyl-pyrrolidine-5-carboxylic acid. 'H NMR (CDCl 3) 5 5.35 (bs, 1H), 4.00 (m, 1H), 3.83 (m, 1H), 3.39 (m, 1H), 3.08 (m, 1H), 2.63 (m, 1H), 2.15 (m, 1H), 2.05 (s, 3H), 1.48 (s, 9H), 1.20-1.45 (m, 7H), 0.85 (, 6H) MS: (M + H) * = 352 3. 8 ,. 17G. (±) - (2R.3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared in accordance with the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-cyano-pyrrolidin- t-butyl ester 5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) penthyl-3- (methoxypropyl) -butyl ester - pi-rrol idi-5-ca rboxí lico. 1 H NMR (de-DMSO) d 9.12 (bs, 1H), 8.05 (m, 1H), 4.38 (m, 1H), 4.23 (m, 1H), 3.88 (m, 1H), 3.68 (m, 1H), 3.00 (m, 1H), 2.55 (m, 1H), 2.05 (m, 1H), 1.88 (s, 3H), 1.10-1.40 (m, 7H), 0.80 (m, 6H) MS: (M + H) * = 296, (MH) = 294, Example 18 (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-ethyl-pyrrolidine-5-carboxylic acid hydrochloride. 18. t-butyl ester of f ±) - (2R.3S.5R.1'S) -1-Benzyl-2- (1-aceta ido-3-ethyl) pentyl-3-vinyl-pyrrolid-5-carboxylic acid. To an iced suspension of methyl triphosphonium bromide (240 ? - -'i! ---- mg, 067 mmol) in 5 mL THF was added potassium t-butyramid (60 mg, 0.54 mmol) under nitrogen. The color immediately changed to bright yellow. After stirring at room temperature for 1 h, (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3 -butyl ester was added. -formyl-pyrrolidine-5-carboxylic acid (100 mg, 0.225 mmol) in 5 mL THF and stirred at room temperature overnight. The reaction was then set with saturated ammonium chloride solution and extracted with ethyl acetate to give the crude product which was purified by chromatography on silica gel using 30% ethyl acetate / hexanes to give the title compound, Oil form (yield: 55 mg, 55%). 1 H NMR (CDCl 3): d 7.45-7.20 (m, 5H), 5.94 (ddd, 1H), 5.24 (d, J = 12Hz, 1H), 4.98 (d, J = 18Hz, 1H), 4.93 (d, J = 10.5HZ, 1H), 4.37 (m, 1H), 4.06 (d, J = 13.5Hz, 1H), 3.80 (d, J = 13.5Hz, 1H), 3.41 (dd, J = 9 Hz, J = 3Hz , 1H), 3.31 (q, J = 135Hz, 1H), 2.60 (m, 1H), 2.26 (m, 1H), 2.00 (s, 3H), 1.45 (s, 9H), 1.40-1.25 (m, 7H) ), 0.82 (m, 6H). MS: (M + H) * = 443 18B. (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-ethyl-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3S, 5R, 1'S) -1-benzyl-2- (1) t-butyl ester. -acetamido-3-ethyl) pentyl-3-vinyl-pyrrole? -carboxylic acid instead of (±) - (2R, 3R, 5R, 1 'S) -1- benzyl-2- (1-acetamido-3-ethyl) penti-3-methoxybutyl ester Methyl-pyrrolidone-5-carboxylic acid. 1H NMR (CDCU): d 5.71 (br, 1H), 4.00 (br, 1H), 3.68 (t, J = 8Hz, 1H), 3. 10 (m, 1H), 2.38 (m, 1H), 1.98 (s, 3H), 1.87 (m, 1H), 1.47 (s, 9H), 1. 55-120 (m, 10H), 0.93 (t, J = 7.5Hz, 3H), 083 (, 6H). MS: (M + H) * = 355 18C. (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-ethyl-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared according to the method which is described in Example 1K, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-ethyl-pyrrolidin-5-carboxylic acid instead of t-butyl ester of the acid (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid. 1H NMR (D20): d 4.30 (br, 1H), 4.25 (t, J = 7.5Hz, 2H), 3.58 (br, 1H), 2. 61 (m, 1H), 2.23 (br, 1H), 2.05 (s, 3H), 1.90 (m, 1H), 1.70-1.20 (m, 9H), 092 (t, J = 7.5Hz, 3H), 0.81 (m, 6H). 20 MS: (M + H) * = 299 Example 19 (±) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-ylpyrrolidololidin-5-carboxylic acid hydrochloride. 19A. acid t-butyl ester (±) - (2R.3S.5R.1 'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (c s-propen-1) -yl) -pyrrolidine-5-carboxylic acid v (±) - (2R, 3S, 5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (frapspropen-1 - i I) - pyrrolidium-5-caboxylic acid. The title compound was prepared according to the method described in Example 18A but using ethyl tp-phenylphosphonium bromide in place of methyl triphenylphosphonium bromide. 1 H NMR (CDCl 3) 5 7.24 (m, 5 H), 5.59 (m, 1 H), 5.36 (dd, J = 11, 7 Hz, 1 H), 5.28 (bs, 1 H), 4.32 (m, 1 H), 4.06 (d , J = 12.9Hz, 1H), 3.80 (d, J = 12.9Hz, 1H), 3.42 (dd, J = 8.5, 2.0Hz, 1H), 3.30 (dd, J = 6.1, 3.1Hz, 1H), 2.88 (m, 1H), 2 29 (m, 2H), 2.01 (s, 3H), 1.64 (dd, J = 6.8, 1.7Hz, 3H), 1.44 (s, 9H), 1.30 (m, 7H), 0.81 (m, 6H). MS: (M + H) * = 457, (M + Na) + = 479, (M-H) - = 455. twenty 19B. acid t-butyl ester (±) - (2R.3S.5R.1'S) -2- (1-acetamido-3-ethyl) pentyl-3-propyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method 5 described in Example 1J, using (±) - (2R, 3S, 5R, 1'S) -1-benzyl-2- (1-) -butyl ester. acetamido-3-ethyl) pentyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid and t-butyl ester of (±) - (2R, 3S, 5R, 1'S) - 1 -benzyl-2- (1 -acetamido-3-ethyl) pentyl-3- (fra / 7s-propen-1-yl) -pyrrolidin-5-carboxylic acid instead of t-butyl ester ( ±) - (2R, 3R, 5R, 1'S) -1-10 be ncil-2- (1 -acetam id o-3-eti I) pen ti I -3-m ethoxy methy1-pyrrolidine-5-carboxylic (yield: 3.5 mg, 54%). MS: (M + H) * = 369, (M + Na) * = 391, (M-H) "= 367. 19C. (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-yl) pentyl-3-propyl-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared in accordance with the method described in Example 1K, using (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-ethyl-pyrrolidin- t-butyl ester. 5- 20 carboxylic acid instead of (±) - (2R, 3R, 5R, 1 'S) -2- (1- acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrole-din-5-carboxylic acid (yield: 3.5 mg, 100%) 1H NMR (DMSO-d6) d 8.10 (d, J = 8.3Hz, 1H), 4.24 (, 1H), 4.17 (m, 1H), 2.43 (m, 1H), 2.19 (m, 1H), 1 89 (s, 3H), 1.70 (, 1H), 1 50-1.20 (, 12H), 0.87 (t, J = 6.8Hz, 3H), 0.84 (t, J = 7.0Hz, 3H), 0.79 (t, J = 7. 3Hz, 3H). MS: (M + H) * = 313, (M + Na) * = 335, (M-H) "= 311.

Example 20 (t) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride.

A. acid t-butyl ester (± - (2R, 3R, 5R, 1'RS) -1-Benzyl-2- (1,2-dihydroxyl) ethyl-3- (f-butylmethyl) lysilyloxymethyl) -pyrrolidine -5- carboxylic acid.

Osmium tetroxide was added a solution at room temperature of (+) - (2S, 3R, 5R) -1-benzyl-2-vinyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidin-5-butyl ester. carboxylic acid (3.5 g, 8.12 mmol) in 60 mL of 8: 1 acetone / water and N-methylmorpholine N-oxide (3.0 g, 25.6 mmol). The reaction mixture was stirred at room temperature for 6 hours and was set with saturated aqueous Na2S203 solution. The mixture was stirred for an additional 10 minutes and the solvent was removed. The brownish residue was partitioned between dichloromethane and water. The organic layer was dried over MgSO4 and concentrated in vacuo to give the intermediate diol as an oil (~ 3 8 g) which was used without further purification. MS- (M + H) * = 466 TB 20B. acid t-butyl ester (±) - (2R.3R, 5R, 1'RS) -2- (1,2-Dihydroxy-ethyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid) The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'RS) -1-benzyl-2- (1,2-dh) t-butyl ester Droxi) etl-3- (f-butyldimet? L-silyloxymethyl) -pyrrolidin-5-carboxylic acid (21.5 g, 46.2 mmol) instead of acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrole-5-carboxylic acid MS: (M + H) * = 367.

TB 20C. t-butyl ester of (±) - (2R.3R, 5R, 1'RS) -1-f-Butoxycarbonyl-2- (1,2-dihydroxy) -ethyl-3- (f-butyldimethylsilyloxymethyl) - pyrrolidin-5-carboxylic acid. The (±) - (2R, 3R, 5R, 1'RS) -2- (1, 2-Dihydroxy) ethyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid t-butyl ester was dissolved. (crude from a previous step) in 160 L of 3: 1 methanol / water and di-tert- butyl-dicarbonate (14.0 g, 64 mmol) was added. The mixture was stirred at room temperature for 72 h. Then the solvent was removed and the residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound as a light yellow solid (yield: 15.4 g, 70%). 1 H NMR (CDCl 3): 50.03 (s, 3 H), 0.05 (s, 3 H), 1.37 (s, 9 H), .42 (s, 9 H), 1.47 (s, 9 H), 1.93 (d, 1 H), 2.30 -2.50 (m, 2H), 3.28 (d, 1H), 3.66-3.43 (m, 4H), 3.85 (dd, 1H), 4.02-4.52 (m, 1H). MS: (M + H) * = 476.

TBDMSO- ^ H P'Bu 'N X O H Boc 0 20D. (±) - (2R.3R, 5R) -1-f-Butoxycarbonyl-2-formyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid t-butyl ester. A solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'RS) -1-f-butoxycarbonyl-2- (1,2-dihydroxy) ethyl-3- (1-butyl) acid was dissolved. -dimethylsilyloxymethyl) -? -rolidolidin-5-carboxylic acid (6.0 g, 12.6 mmol) in tetrahydrofuran (THF) / water (110 mL) 6: 1, treated with sodium periodate (4.4 g, 20.6 mmol). The mixture was stirred at room temperature for 3 hours and diluted with ethyl acetate, washed with water, dried over MgS? , filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel using 20% ethyl acetate / hexanes to give the title compound as a white waxy solid (yield: 4.4 g, 78.6%). 1H NMR (CDCb) (mixture of two rotamers): 5 0.05 and 0.06 (two s, 6H), 0.88 and O 90 (two s, 9H), 1 42 and 1.44 (two s, 9H), 1.47 and 1.48 (two s, 9H), 1.89 -1 99 (m, 1H), 237 - 2. 3 (m, 2H), 3.54-367 (m, 2H), 4.02-4.34 (m, 2H), 9.43 and 9.53 (two d, 1H) MS: (M + H) * = 444. 20E. (±) - (2R, 3R, 5R, 1'RS) -1-f-Butoxycarbonyl-2-l-hydroxy-3-methyl) butyl-3- (f-butyldimethylsilyloxymethyl) t-butyl ester -pyrrolidine-5-carboxylic acid. A solution of (±) - (2R, 3R, 5R) -1-f-butoxycarbonyl-2-formyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid t-butyl ester ( 7.1 g, 16.03 mmol) in diethyl ether (75 mL) with isobutyl magnesium chloride (24 mL, 2.0 M in ether, 48 mmol) at 0 ° C for 2.5 hours. The reaction was set with saturated ammonium chloride solution and diluted with ethyl acetate. The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was used in the next step without further purification. MS: (M + H) * = 502 20F. (±) - (2R, 3R, 5R) 1-f-Butoxycarbonyl-2- (1-oxo-3-methyl) butyl-3- (f-butyl-ldimethylsilyloxymethyl) -pyrrolidin- acid t-butyl ester 5-carboxylic acid A solution of oxalyl chloride (16 mL, 2M in CH2Cl2) in 100 mL of anhydrous dichloromethane was prepared and kept under a nitrogen atmosphere at -78 ° C. DMSO (4.26 mL, 64.1 mmol) was slowly added to the solution. The mixture was stirred for 15 minutes and reacted with (±) - (2R, 3R, 5R, 1'RS) -1-f-butoxycarbonyl-2- (1-hydroxy-3-methyl) t-butyl ester. ) butyl-3- (f-butyldimethylsilyloxy-methyl) -pyrrolidine-5-carboxylic acid f-butyl in 30 mL of anhydrous dichloromethane. The solution was stirred for 1 hour and triethylamine (17 mL, 128 mmol) was slowly added to the reaction mixture. The solution was allowed to warm slowly to room temperature, was fired with saturated sodium bicarbonate solution and diluted with dichloromethane. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5-10% ethyl acetate / hexanes to give the title compound (yield: 6.3 g, 78.8%). H NMR (CDCI3): 5 0.07 (m, 6H), 0.81 - 0.96 (m, 15H), 1.40 and 1.42 (two s, 9H), 1.46 and 1.47 (two s, 9H), 1.72-1 82 (m, 1H), 2.15-2.45 (m, 4H), 3.47-369 (, 1H), 428-4.46 (m, 2H) MS: (M + H) * = 500 20G acid t-butyl ester (±) - (2R.3R.5R.1'RS) -1-f-Butoxycarbonyl-2- (1-arnino-3-methylbutyl-3- (f-butyl dimethyl-l-loxyrnethyl) -pyrrolidone-5-carboxylic acid The title compound was prepared according to the method described in Example 1F, using (±) - (2R, 3R, 5R) 1 -butyl ester f -butoxycarbonyl-2- (1-oxo-3-methyl) butyl-3- (f-butyl-dimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, t-butyl ester, 5R) -1-benzyl-2- (1-oxo-3-ethyl) pentyl-3- (f-butyldimethyl-silyloxymethyl) -pyrrolidine-5-carboxylic acid (yield: 0.54 g, 34.1%). MS: (M + H) * = 501. 20H. acid t-butyl ester (±) - (2R, 3R.5R, 1'S) -1-r-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (f-butyl and methyl silyl) oxymethyl) -pi rrol id in-5-carboxylic acid. The title compound was prepared according to the method described in Example 1G, using acid t-butyl ester (±) - (2R, 3R, 5R, 1'RS) -1-r-butoxycarbonyl-2- (1-amino-3-methyl) butyl-3- (f-butyldimethylsilyloxymethyl) - pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'R) - and t-butyl ester of the acid (±) - uea-E- .. (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-amino-3-ethyl) pentyl-3- (f-butyldimethylsilyloxymethyl) -1-pyrrolidine-5-carboxylic acid (yield - 462 mg, 79.0%). (±) - (2R, 3R, 5R, 1'S) H NMR (CDCI3): d 0.03 and 0.04 (two s, 6H), 0.86 (s, 9H), 0.89 and 0.95 (two d, 6H), 1.04 (m , 1H), 1.17 -1.25 (m, 2H), 1.44 (s, 9H), 1.46 (s, 9H), 1.86 (m, 1H), 1.99 (s, 3H), 2.07 (m, 1H), 2.30 ( m, 1H), 3.48 (m, 1H), 3.61 (m, 1H), 3.67 (m, 1H), 4.16 (m, 1H), 4.27 (m, 1H), 7.35 (br d, 1H). MS: (M + H) * = 543. twenty!. t-butyl ester of f ±) - (2R.3R.5R.1'S) -1-f-Butoxylcarbonyl-2-M-acetamido-3-methyl) butyl-3- (hydroxymethyl) -pyrrolidin-5- carboxylic The title compound was prepared according to the method described in Example 1H, using (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-t-butyl ester -2- (1-Acetamido-3-ethyl) butyl-3-t-butyldimethylsilyloxymethyl-pyrrolidine-5-carboxylic acid. MS: (M + H) * = 429. 20J. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrole-din-5-carboxylic acid . The title compound was prepared according to the method described in Example 2A, using (+) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- ( 1 -acetam-ido-3-ethyl) pentyl-3-h id roxy-methyl-pyrrolidine-5-carboxylic acid (yield: 1.5 g, 91%). H NMR (CDCI3): d 0.92 and 0.94 (two d, 6H), 1.07 (m, 1H), 1.23-1.33 (m, 2H), 1.43 (s, 9H), 1.44 (s, 9H), 1.64 (m , 1H), 2.03 (s, 3H), 2.39 (m, 1H), 2.46 (m, 1H), 3.18 (m, 1H), 4.19 (m, 1H), 4.32 (m, 1H), 4.39 (m, 1H), 7.12 (br d, 1H). MS: (M + H) * = 427 20K acid t-butyl ester (±) - (2R.3S.5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid. To a suspension of methyl triphosphonium bromide (125.6 mg, 0.35 mmol) in 3 ml of anhydrous toluene was added t-butoxide. potassium (1.0 M in THF, 0.31 mmol) per drop at room temperature. After stirring for 16 hours, (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-butyl-3-butyl ester was added. formyl-pyrrolidine-5-carboxylic acid (30 mg, 0.070 mmol) in 3 ml of toluene by dropping and stirred for 0.5 hour. The reaction was set with saturated ammonium chloride solution and diluted with methylene chloride. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using ethyl acetate to give the title compound, as a white foamy solid (yield: 23.7 mg, 79.4%). 1 H NMR (CDCl 3): 50.92 (m, 6 H), 1.26 (m, 2 H), 1.44 (s, 9 H), 1.47 (s, 9 H), 1.65 (m, 1 H), 1.97 (s, 3 H), 2.43 ( m, 2H), 3.56 (m, 1H), 4.15 (m, 2H), 4.32 (m, 1H), 5.11 (m, 1H), 5.15 (m, 1H), 5.75 (m, 1H), 7.35 (br , 1 HOUR). MS: (M + H) * = 425. 20L. (±) - (2R, 3S.5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3-vinyl-pyrrolidin-5-carboxylic acid hydrochloride. The title compound was prepared according to the method described in Example 1K, using (±) - (2 R, 3S, 5 R, 1 'S) - 1-f-bu toxi-t-butyl ester carbon i l-2- (1 -acetamido-3-meti) bu til-3- vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine) t-butyl ester - 5-carboxylic (yield: 16.0 mg, 99.1%). 1 H NMR (DMSO-d 6): d 0.82 (d, 3 H), 0.88 (d, 3 H), 1.29 (m, 1 H), 1.42 5 (m, 1 H), 1.57 (m, 1 H), 1.87 (s, 3 H) ), 1.91 (m, 1H), 2.40 (m, 1H), 2.90 (m, 1H), 4.20 (m, 1H), 4.32 (m, 1H), 5.08 (dd, 1H), 5.17 (dd, 1H) , 5.72 (ddd, 1H), 8.09 (d, 1H), 9.16 (br s, 1H), 9.28 (br s, 1H). MS: (M + H) * = 269.

Example 21 Hydrochloride of (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-hydroxymethyl I-pyrrole I-di-5- carboxylic acid . 21A. acid t-butyl ester (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-eyl l) pentyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3-hydroxymethyl-20-pyrrolidine-5-carboxylic acid in place of (±) - (2 R, 3 R, 5 R, 1'S) -1-benzyl-2-t-butyl ester - (1 -acetam id o -3-ethyl) penyl-3-methoxymethylpyrro lidin-5-carboxylic acid. MS: (M + H) * = 471 21B. (±) - (2R, 3R, 5R, 1 'S) -2- (1-Acetamido-3-ethyl) pentyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid hydrochloride. The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) t-butyl ester ) pentyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-butyl ester methoxymethyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-dβ): d 8.15 (d, J = 9Hz, 1H), 4.28-4.15 (, 2H), 3.95-3.45 (m, 4H), 2.35 (m, 1H) , 1.98 (m, 1H), 1.89 (s, 3H), 1.50-1.45 (m, 7H), 0.81 (t, J = 7.4Hz, 3H), 0.77 (t, J = 7.5Hz, 3H). MS: (M + H) * = 301, (M-H) = 299 Example 22 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (pyrrol-1-yl) -pyrrolidine-5-carboxylic acid hydrochloride. 22A. t-butyl ester of (t) - (2S.3R.5R.1'S) -1-Benzyl-2- (1-Acetamido-3-ethyl) pentyl-3- (2-trimethylsilylcarboxylamino) - pyrrolidin-5-carboxylic acid. (±) - (2R, 3R, 5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid t-butyl ester ( 80 mg, 0.18 mmol), prepared according to the procedure of Example 2B, with diphenylphosphoryl azide (0.047 mL, 0.216 mmol), 2-trimethylsilylethanol (0.034 mL, 0.234 mmol), and triethylamine (0.030 mL, 0.216 mmol) in toluene (2 mL) at 75 ° C for 15 hours. The reaction was concentrated in vacuo and the resulting residue was purified by chromatography on silica gel using 25% ethyl acetate / hexanes to give the title compound, as a yellow oil yield: 46 mg, 45%) MS. (M + H) * = 576, (M + Na) * = 598, (M-H) "= 574. 22B. acid t-butyl ester (±) - (2S, 3R.5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-aminopyrrolidone-5-carboxylic acid The title compound is prepared according to the method described in Example 1H, using (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3- (2-trimethylsilylethoxycarbonyl) -pyrrolidine-5-carboxylic acid in place of the (+) - (2R, 3R, 5R, 1'S) t-butyl ester -2- ( 1-acetamido-3-ethyl) pentyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid. MS- (M + H) * = 432, (M-H) "= 430. 22C. acid t-butyl ester (±) - (2S.3R.5R.1'S) -1-Benzyl-2- (1-Acetamido-3-ethyl) pentyl-3- (pyrrol-1-yl) -pyrrolidine -5-carboxylic acid. The acid (±) - (2S, 3R, 5R, 1'S) -1- Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-amino-pyrrolidone was reacted 5-carboxylic acid (34 mg, 0.078 mmol) with 40% succinic dialdehyde in water (50 mg, 0.234 mmol), acetic acid (0.00044 mL, 0.0078 mmol), and 4A molecular filters (200 mg) in toluene (2 mL) ) at RT for 3 hours. The reaction was concentrated in vacuo and the resulting residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound, as an oil (yield: 7.1 mg, 19%) MS: (M + H) * = 482, (M + Na) * = 504, (MH) "= 480. 22D. (±) - (2S, 3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (pyrrol-1-yl) -pyrrolidine-5-carboxylic acid t-butyl ester. The title compound is prepared according to the method described in Example 1J, using (±) - (2S, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3- (pyrrol-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2-t-butyl ester - (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 3.5 mg, 61%). MS: (M + H) * = 392, (M-H) '= 390. 22E (±) - (2S, 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (pyrrol-1-yl) -pyrrolidin-5-ca-carboxylic acid hydrochloride . The title compound was prepared according to the method described in Example 1K, using (±) - (2S, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) t-butyl ester ) pentyl-3- (pyrrol-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) t-butyl ester -2- (1-acetamido-3-) ethyl) pentyl-3-methoxymethyl-pyrrolidin-5-carboxylic acid (yield: 3.5 mg, 100%). H NMR (D20) d 7.48 (bs, 1H), 6.77 (bs, 2H), 5.97 (bs, 2H), 4.33 (m, 1H), 3.70 (m, 1H), 3.07 (m, 1H), 2.43 ( m, 1H), 1.92 (m, 1H), 1.75 (s, 3H), 1.55 (m, 1H), 1.35-1 10 (m, 7H), 0.81 (m, 3H), 0.75 (m, 3H) MS : (M + H) * = 336, (MH) - = 334.

EXAMPLE 23 (±) -f2R, 3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (1-cs-N-hydroxy-amino) ethyl-pyrrolidine- hydrochloride 5-carboxylic. 23A. t-butyl ester of (t) - (2R, 3R, 5R, 1'S) -1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (1-cs-N-hydroxyimino) ethyl ester pyrrolidin-5-carboxylic acid. Reacted -butyl ester of the acid (±) - (2R, 3R, 5R, 1'S) 1-Benzyl-2- (1 -acetamido-3-ethyl) pentyl-3-acetyl-pyrrolidin-5-ca rboxy I ico (45 mg, 0.1 mmol) prepared according to the method of Example 8B in methanol / methylene chloride (3/1) with a solution of hydroxylamine hydrochloride (21 mg, 0.3 mmol) and sodium hydroxide (12 mg , 0.3 mmol) in methanol (2 L) for 2 h. The reaction was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over MgS? , it was filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 40% ethyl acetate / hexanes to give the title cis-oxime compound (lower Rf spot on TLC), as an oil (yield: 35 mg, 75%), as well as the trans-oxime compound of the titer (upper Rf spot in TLC), in the form of oil (yield: 13 mg, 25%). MS: (M + H) * = 474 23B t-butyl ester of (±) - (2R.3R.5R.1'S) -2- (1-acetamido-3-ethyl) pentyl-3 (1-c / 'sN-hydroxyimine) ) ethyl pyrrolid? n-5-carboxyl? co. The title compound is prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-ethyl) pentyl-3- (1-c / sN-hydroxyimino) ethyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) t-butyl ester -1- benzyl-2- (1-acetamido-3-etyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid. H NMR (CDCl 3): d 3.92 (br, 1H), 3.70 (m, 2H), 2.82 (m, 1H), 2.38 (m, 1H), 1.88 (s, 3H), 1.78 (s, 3H), 1.39 (s, 9H), 1.40-1.20 (m, 7H), 0.76 (m, 6H). MS: (M + H) * = 384 23C. (±) -f2R.3R.5R.1'S) -2- (1-acetamido-3-ethyl) pentyl-3-f1-c) sN-hydroxyimino) ethyl-pyrrolidine-5-carboxylic acid hydrochloride The compound of the title is prepared according to the method described in Example 1K, using acid t-butyl ester (+) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-et? L) pentyl-3- (1-c; sN-hydroxyimino) ethyl-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidin-5-carboxylic acid t-butyl ester . 5 H NMR (D20) - d 4.35 (m, 1H), 4.00 (m, 1H), 3.80 (m, 1H), 371 (m, 1H), 3.63 (m, 1H), 3.13 (q, J = 8.4 Hz, 1H), 2.64 (m, 1H), 2.18 (m, 1H), 1.97 (s, 3H), 1.85 (s, 3H), 1.50-1.10 (m, 7H), 0.77 (m, 6H). MS: (M + H) * = 328 Example 24 (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-hi-roxyimino) methyl-pyrrolid-5 hydrochloride -carboxylic .NOH 24A. acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-etiDpen ti l-3- (N-hydroxyimino) me ti I-pyrro lidin-5-carboxylic acid The (±) - (2R, 3R, 5R, 1'S) -1- Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester was reacted. (18 mg, 0.051 mmol), prepared according to the method of Example 2A, with hydroxylamine hydrochloride (7 mg, 0.11 mmol) in 1N NaOH in methanol (3 mL) at 25 ° C for 1.5 hours. The reaction was set with aqueous solution of ammonium chloride (3ml) and water (3ml) and extracted with t-chloromethane (2x 10 ml). The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% methanol in dichloromethane to give the title compound, as an oil (yield: 6 mg, 32%). MS: (M + H) * = 370 24B (±) - (2R, 3R, 5R.1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (N-hydroxyamino) methyl-pyrrolidine-5-carboxylic acid hydrochloride The title compound is prepared according to the method described in Example 1 K, using (±) - (2 R, 3 R, 5 R, 1'S) t-butyl ester (2-acetic acid) 3-ethyl) penyl-3- (N-hydroxy imino) methyl-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-) 3-ethyl) pentyl-3- (methoxy ethyl) -pyrrolidine-5-carboxylic acid.

Example 25 Acid (±) - (2R.3R, 5R, 1'S) -2-p-Acetamido-3-et? L) pentyl-3- (methox? Im?) Methyl-? -rolidolid-5-carboxylic acid 25A. Acid (±) - (2R.3R.5R.1'S) 1-Benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (methoxyimino) methyl-pyrrolidine-5-carboxylic acid T-butyl ester was reacted of (±) - (2R, 3R, 5R, 1'S) 1- Benzyl-2- (1-acetamido-3-ethyl) pentyl-3-cyano-pyrrolidine-5-carboxylic acid (20 mg, 0.045 mmol), prepared according to the method of Example -17E, with hydrogen chloride (0.45 mmol) in ether (2 mL) and methanol (0.1 mL) at 0 ° C for 5 hours. The reaction was neutralized with aqueous ammonium hydroxide solution and purified on silica gel with 3% methanol in dichloromethane to give the title compound, as a white solid (yield: 5 mg, 26%). 15 MS: (M + H) * = 418 25B. Acid (±) - (2R.3R.5R.1'S) -2- (1-Acetamido-3-ethyl-3- (methoxy-amino) methy1-pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) t-butyl ester 1-Benzyl-2- (1-acetamido-3-ethyl) pentyl- 3- (imino-methoxymethyl) -pyrrolidine-5-carboxylic acid, instead of t-butyl ester of the acid (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pent? L-3-methoxymethyl-pyrrolidine-5-carboxylic (yield: 39 mg, 96% ) H NMR (DMSO-de) 5 7.52 (d, J = 8.7 HZ, 1H), 7.15 (s, 1H), 6.77 (s, 1H), 3. 68 (m, 1H), 3.61 (s, 3H), 3.22 (m, 1H), 2.51 (m, 1H), 2.23 (m, 1H), 1. 82 (m, 1H), 1.78 (s, 3H), 1.40 (m, 1H), 1.26 (m, 3H), 1.13 (m, 3H), 0. 78 (t, J = 6.5HZ, 3H), 0.72 (t, J = 6.5HZ, 3H) MS: (M + H) * = 328 EXAMPLE 26 (±) - (2R.3R.5R.1 'S) -2- (1-Acetamido-3-met? L) but? L-3- (hydroxyacet? 0 -pyrrol? D? N) Hydrochloride -5-carboxylic acid. 26A. acid t-butyl ester (±) - (2R.3R.5R.1'S.1"RS) -1-f- Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (1, 2-) dihydroxy) ethyl-pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 20A using (±) - (2R, 3R, 5R, 1'S) t-butyl ester - 1 -f-Butoxycarbonyl-2- (1 -aceta-my-do-3-methyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of the (±) - (2S, 3R, 5R) -butyl ester - 1-Benzyl-2-vinyl-3- (f-butyldimethylsilyloxymethyl) -pyrrolidine-5-carboxylic acid. 26B. acid t-butyl ester (±) - (2R, 3R.5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (hydrox? acetyl) -pyrrole? din -5-carboxylic acid.

The (±) - (2R, 3R, 5R, 1'S, 1"RS) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- acid is reacted. (1,2-dihydroxy) ethyl-pyrrolidine-5-carboxylic acid with dibutyltin oxide in methanol according to the procedure of Kong in J. Carbohydrate Chem. 1993, p. 557. The reaction was concentrated and the residue was redissolved in dichloromethane which was reacted with bromine as described in the above reference to give the title compound. 26C. (±) - (2R, 3R.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (hydroxyacetyl) -pyrrolidine-5-carboxylic acid hydrochloride. The title compound is prepared according to the method described in Example 1K, using (+) - (2 R, 3 R, 5 R, 1'S) - 1-f- bu toxi carbon t-butyl ester i l-2- (1 -acetamido-3-methy) buty I-3-hydroxyacetyl-pyrrolidine-5-carboxylic acid in place of (+) - (2R, 3R, 5R, 1'S) t-butyl ester - 2- (1-Acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid.

EXAMPLE 27 (±) - (2S, 3R, 5R, 1 'S) -2-l-Acetamido-3-methyl) butyl-3-amino-p-rrolidin-5-carboxylcocidehydrochloride. 27A. (±) - (2S, 3R.5R, 1'RS) -1-Benzyl-2- (1-hydroxy-3-methyl) butyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 9D, but using isobutylmagnesium bromide in place of 3-pentylmagnesium bromide. 27B. (±) - (2S.3R.5R.1'S) -1-Benzyl-2-f1-acetamido-3-methyl) butyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Examples 9E-H using (±) - (2R, 3R, 5R, 1'RS) -1-benzyl-2- (1) -butyl ester. -hydroxy-3-methyl) butyl-3-benzyloxycarbonylamino-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'RS) -1-benzyl-2-t-butyl ester - (1-hydroxy-3-ethyl) pentyl-3-benzylcarboxylamino-pyrrole-dm-5-carboxylate as the initial material of the sequence in Example 9E. 27C. (±) - (2S.3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3-amino-pyrrolidine-5-carboxylic acid dihydrochloride The title compound was prepared in accordance with the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl-3-amino-pyrrolidin- t-butyl ester 5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3- (methoxymethyl) -pyrrolidine-5-carboxylic acid t-butyl ester . 1H NMR (de-DMSO) d 8.64 (bs, 1H), 8.32 (bs, 1H), 8.23 (bs, 1H), 8.18 (d, J = 6Hz, 1H), 4.79 (d, J = 7Hz, 1H) , 4.42 (m, 1H), 4.33 (m, 1H), 4.21 (m, 1H), 4.07 (m, 1H), 3.76 (m, 2H), 2.73 (m, 2H), 1.92 (, 3H), 0.80 -0.97 (m, 7H). MS (M + H) * = 258 Example 28 (±) - (2R, 3R, 5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3-methoxycarbonyl-1-pyrrolidine-5-carboxylic acid hydrochloride. 28A. acid t-butyl ester (±) - (2R.3R, 5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-ca rboxi lp? rrolidin-5-carboxylic acid . The title compound was prepared according to the method described in Example 2B, using (+) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-) acid t-butyl ester acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid. 28B. acid t-butyl ester (±) - (2R.3R, 5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 2C, using (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-met? l) butyl-3- carboxyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-carboxylic acid t-butyl ester -Impro-id-n-5-caboxicole. 28C. (±) -f2R acid hydrochloride, 3R.5R.1'S -2- (1-Acetamido-3-methyl) butyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 2E, using (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3-methoxycarbonyl-pyrro-udin-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) t-butyl ester -2- (1-acetamido-3-) ethyl) pentyl-3-methoxycarbonyl-? irolidine-5-carboxylic acid. 1 H NMR (DMSO-d 6): d 8.24, 8.08 (d, J = 9Hz, 1H), 4.44, 4.36 (m, 1H), 4.25, 4.15 (m, 1H), 3.98, 3.88 (m, 1H), 3.65 , 3.64 (s, 3H), 3.18, 3.10 (m, 1H), 2.57, 2.20 (m, 2H), 1.87, 1.83 (s, 3H), 1.57 (m, 2H), 1.36 (m, 1H), 0.88 (d, J = 7.5Hz, 3H), 0.82 (d, J = 7.5Hz, 3H). MS: (M + H) * = 301 EXAMPLE 29 (± - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3 - (? M? Dazol-2-? L) -pyrrolidine-5-carboxylic acid diclohydrate . 29A. (+) - (2R.3R.5R, 1'S) -1-Benzyl-2- (1-acetamido-3-methyl) butyl-3- (imidazol-2-yl) -pyrrolidin-5-butyl ester. -carboxylic The title compound was prepared according to the method described in Example 15A, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1) t-butyl ester. -acetamido-3-met? l) butyl-3-formyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2-t-butyl ester ( 1-Acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid (yield: 27.4 mg, 83.%). MS: (M + H) * = 455. 29B. acid t-butyl ester (± - (2R, 3R, 5R.1'S) -2- (1-Acetamido-3-methylobutyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid The title compound is Prepared according to the method which is described in Example 15B, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-methyl) butyl- t-butyl ester 3 - (? Midazol-2-yl) -pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-) t-butyl ester 3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid (yield: 19.1 mg, 95.5%). MS: (M + H) * = 365. 29C (±) - (2R, 3R.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (midazol-2-yl) -pyrrolidine-5-carboxylic acid dihydrochloride. The title compound was prepared according to the method described in Example 15B, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-methyl) butyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl- t-butyl ester 2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-d 6): G 0.76 (d, J = 6.6 Hz, 3 H), 0.82 (d, J = 66 Hz, 3 H), 1.18 (t, 2 H), 1.44 (m, 1 H), 1.71 (s) , 3H), 2.43-2.47 (m, 1H), 2.80 (m, 1H), 3.83 (m, 1H), 4.05 (m, 1H), 4.28 (m, 1H), 4.55 (t, 1H), 7.65 ( s, 2H), 8.03 (d, J = 8.4 Hz, 1H). MS: (M + H) * = 326.

EXAMPLE 30 (±) - (2R.3R.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (imidazol-4-yl) -pyrrolidine-5-carboxylic acid hydrochloride. 30A. t-butyl ester of (±) - (2R, 3R, 5R, 1'SM-f-Butoxycarbonyl-2- (1 -acetam id 0-3-methy) butyl-3-carboxyl-pi rrol id i n- 5-ca rboxí lico.

The title compound was prepared according to the method described in Example 2B, using (+) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid prepared according to the method described in Example 20J in place of (±) - (2R, 3R, 5R) t-butyl ester , 1, S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid (yield: 129.5 mg,> 100%). MS: (M + H) * = 443. ? 30B. (±) - (2R, 3R, 5R, 1 'S) -1-Benzyl-2- (1-acetamido-3-methyl) butyl-3-diazoacetyl-pyrrolidine-5-carboxylic acid t-butyl ester. The title compound was prepared according to the method described in Example 12A, using (±) - (2 R, 3 R, 5 R, 1'S) - 1 -benzyl-2-t-butyl ester (1 -acetam id or -3-methyl) butyl-3-carboxyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl- t-butyl ester 2- (1-Acetamido-3-ethyl) pentyl-3-carboxyl-pyrrolidine-5-carboxylic acid (yield: 218.8 mg, 100%). MS: (M + H) * = 458. 30C. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-methyl) butyl-3-bromoacetyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 12B, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) -butyl ester. -3-methyl) butyl-3-diazoacetyl-pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-) acid t-butyl ester 3-ethyl) pentyl-3-diazo- Acetyl-pyrrolidine-5-carboxylic acid (yield: 1072 mg, 45.5%). 1 H NMR (CDCl 3): 0 0.90 (d, 6 H), 1.26 - 1.35 (m, 3 H), 1.42 (s, 9 H), 1. 95 (s, 3H), 2.25 (m, 2H), 3.11 (m, 1H), 3.54 (dd, 1H), 3.69 (m, 1H), 3. 93 (dd, 2H), 4.11 (d, 1H), 427 (m, 1H), 4.35 (d, 1H), 5.05 (br d, 1H), 7.25-7.32 (m, 5H). MS: (M + H) * = 509. 30D. acid t-butyl ester (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1-acetamido-3-methyl) butyl-3- (imidazol-4-yl) -pyrrolidine -5-carboxylic acid.

The title compound was prepared according to the method described in Example 12C, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetam) t-butyl ester. Do-3-methyl) butyl-3-bromoacetyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (t) butyl ester ( 1-acetamido-3-ethyl) pentyl-3-bromoacetyl-pyrrolidine-5-carboxylic acid (yield: 32.3 mg, 60.4%). MS: (M + H) * = 455. 30E. (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) -butyl-3- (imidazol-4-yl) -pyrrolidine-5-carboxylic acid t-butyl ester . The title compound was prepared according to the method described in Example 1J, using (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido) t-butyl ester -3-methy1) butyl-3- (imidazol-4-yl) -p-rrolidin-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) t-butyl ester -1 -benzyl-2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 23.9 mg, 96.2%). 1 H NMR (CDCl 3). D 0.87 (d, 3H), 0.89 (d, 3H), 1.26 (m, 1H), 1.41 (m, 2H), 1.46 (s, 9H), 1.59 (m, 1H), 1.93 (s, 3H), 2.62 (m, 1H), 3.30 (m, 1H), 3.54 (m, 1H), 3.79 (m, 1H), 4.01 (m, 1H), 6.11 (br d, 1H), 6.89 (s, 1H), 7.63 (s, 1H). MS: (M + H) * = 365. 30F. (±) - (2R, 3R.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (im-dazol-4-yl) -pyrrolidine-5-carboxylic acid dihydrochloride. The title compound was prepared according to the method which is described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl-3- (imidazole-4) t-butyl ester -? l) -pyrrolidine-5-carboxyl? co in place of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl- t-butyl ester 3- (methoxymethyl) -pyrrolidine-5-carboxylic acid to give the title solid compound (yield: 24.4mg, 100%). 1 H NMR (DMSO-d 6): G 0.76 (d, J = 3.6 Hz, 3 H), 0.88 (d, J = 3.6 Hz, 3H), 1.22 (m, 1H), 1.28 (m, 1H), 1.48 (m, 1H), 1.79 (s, 3H), 2.32 (dt, 1H), 2.71 (dt, 1H), 3.68 (m, 1H) ), 3.96 (m, 1H), 4.28 (m, 1H), 4.51 (t, 1H), 7.63 (s, 1H), 8.23 (d, J = 5.1 Hz, 1H), 9.10 (s, 1H), 9.67 (br s, 1H), 14.51 (br s, 1H). MS: (M + H) * = 309.

Example 31 (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3-ythiazol-4-yl) -pyrrolidine-5-carboxylic acid dihydrochloride. 31A. acid t-butyl ester (±) - (2R, 3R, 5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (thiazol-4-yl) -pyrrolidine-5-carboxylic acid.

Reacted t-butyl ester of (±) - (2R, 3R, 5R, 1 'S) -1-t-Bu toxic rbon 11-2- (1 -acetam id o-3-methyl) bu ti l -3-bromoacetyl pyrrolid i n- -carboxylic acid (36.5 mg, 0.07 mmol) with thioformamide (21.4 mg, 0.35 mmol) in ethanol (5 ml) at reflux for 4 hours. The reaction was concentrated in vacuo. The residue was treated with 5 ml of aqueous NaHCO 3 solution and extracted with dichloromethane (4 x 5 ml). The organic layers were washed with brine, dried over Na 2 SO 4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using ethyl acetate to give the title compound, as a white solid (yield: 23.8 mg, 70.4%). MS: (M + H) * = 482. 31B. (+) - (2R, 3R.5R, 1'S -2- (1-Acetamido-3-methyl) butyl-3- (thiazol-4-yl) -pyrrolidine-5-carboxylic acid hydrochloride. prepared according to the method described in Example 1K, using (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-) t-butyl ester methyl) butyl-3- (thiazol-4-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2 R, 3 R, 5R, 1'S) t-butyl ester) -2- (1 -aceta) mido-3-eti I) penyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 18.5 mg, 100%). 1 H NMR (DMSO-d6): at 0.62 (d, J = 4.2 Hz, 3H ), 0.72 (d, J = 4.2 Hz, 3H), 1.05 (m, 1H), 1.12 (m, 1H), 1.30 (m, 1H), 1.72 (s, 3H), 2.14 (dt, 1H), 2.59 (dt, 1H), 3.69 (m, 1H), 3.92 (br m, 1H), 4.21 (m, 1H), 4.38 ^^ gm (br m, 1H), 746 (d, J = 1 2 Hz, 1H), 802 (d, J = 5.1 Hz, 1H), 9.04 (d, J = 1.2 Hz, 1H), 939 (br s, 1H ), 9.48 (br s, 1H) MS: (M + H) * = 326.

Example 32: (+ - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (ti azol-2-yl) -pyrol lid i n-5- dihydrochloride carboxylic 32A. acid t-butyl ester (±) - (2R.3R.5R.1 'S) -1-f-Butoxycarbonyl-2- (1 -acetamido-3-methyl) bu ti l-3-carbamoyl-pyrrolidin- 5-carboxylic. The t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1- f- Butoxycarbonyl-2- (1 -acetamido-3-methyl) butyl-3-carboxyl-pyrrolidine was reacted. -5- carboxylic acid (0.258 g, 0.584 mmol) with isobutyl chloroformate (80 mg, 0.84 mmol) and N-methylmorpholine (59 mg, 0.584 mmol) in THF (10 mL) at 0 ° C for 0.25 hours. Aqueous ammonium hydroxide solution (.39 mL) was added and the reaction was stirred at 0 ° C for 0.5 hour. The reaction was diluted with ethyl acetate. The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using 100% ethyl acetate to 5% methanol-ethyl acetate to give the title compound, as a glass (yield- 182 mg, 707%) 1H NMR (CD3OD) 5 4.70 (m, 1H), 4.36 (q, J = 3 Hz, 1H), 405 (m, 1H), 2.87 (q of t, J = 9 and 3 Hz, 1H), 252 (m, 1H), 236 (m, 1H) 1.94 (d, 3H), 163 (m, 1H), 1.41-1.53 (m, 18H), 1.3 (m, 2H), 0.9-0.18 (m, 6H) MS: (M + H) * = 442 32B. t-butyl ester of (±) - (2R, 3R, 5R, 1 'S) - 1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-thiocarbamoyl-pyrrolene din -5-carboxylic acid.

The (±) - (2R, 3R, 5R, 1'S) -1 - / - Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-carbamoyl-pyrrolidin was reacted with the t-butyl ester. -5-carboxylic acid (70 mg, 0.159 mmol) with P2S10 (8.5 mg, 0.019 mmol) in 4 ml tetrahydrofuran and 1 ml of methylene chloride at room temperature. After 1.25 hrs, 9.6 mg of P S10 was added. The starter material had been consumed after 2 hrs. The mixture was diluted with ethyl acetate, washed with water and brine, dried over Mg 4. it was filtered and concentrated. TLC analysis showed two spots and the mass spectrography indicated that it was a mixture of mono-thio and di-thio compounds. The material was used in the following reaction without further purification MS: (M + H) * = 458, 474 32C. t-butyl ester of (+) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (t-azol-2-) il) -pyrrolidine-5-carboxylic acid.

Reacted t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-f- Bu toxic rbonyl-2- (1-a ceta mido-3-meti) bu ti l-3- thiocarb amoil-pyrro lidin-5-carboxylic acid (73 mg, o.16 mmol) with chloroacetaldehyde (50% in water) (0.02 ml, 0.16 mmol) in 5 ml of acetone at 75 ° C. Magnesium sulfate (0.9 g) and additional chloroacetaldehyde were added at intervals for the next 5 hr until the conversion of all the initial material. The reaction was diluted with ethyl acetate, washed with water, and brine, dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 100% ethyl acetate to give the title compound, in the form of glass (yield: 12.6 mg, 16.3%). 1 H NMR (CDCl 3) d 7.69 (m, 1 H), 7.45 (m, 1 H), 4.44 (m, 1 H), 4.28 (m, 2 H), 3.52 (m,! H), 2. 7 (m, 1 H) , 2.5 (m, 1H), 1.99 (s, 3H), 1.44 (s, 9H), 1.37 (s, 9H), 1.27 (m, 3 H), 0.95 (m, 6 H). MS: (M + H) * = 482 32D. (±) - (2R, 3R, 5R, 1'S) -1- f-Butoxycarbonyl-2- (1-acetamido-3-methyl) -butyl-3- (thiazol-2-yl) -pyrrolidin- acid dihydrochloride 5-carboxylic The title compound was prepared according to the method described in Example 1K, using (±) - (2 R, 3 R, 5 R, 1'S) - 1-f-bu toxy carbo-t-butyl ester nyl-2- (1 -acetam-ido-3-methyl) -butyl-3- (thiazol-2-yl) -pyrrolidin-5-carboxylic acid in place of (+) - (2R) -butyl ester , 3R, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 10.1 mg, 82%). 1H NMR (DMSO-d6) d 8.1 (d, J = 10Hz, 1H), 7.79 (d, J = 4Hz, 1H), 7.69 (d = 4 Hz, 1H), 4.49 (t, J = 7.5, 1H) , 4.22 (m, 1H), 4.14 (t, J = 9Hz, 1H), 4.01 (q, J = 10Hz, 1H), 2.80 (m, 1H), 2.25 (m, 1H), 1 78 (s, 3H) ), 1.47 (m, 1H), 1.25 (m, 2H), 0.83 (d, J = 6.2Hz, 3H), 0.75 (d, J = 6.2Hz, 3H) MS: (MH) "= 324, (2M) -1) "= 649, (M + 35) + = 360 EXAMPLE 33 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R.1 'S) -2- (1-acetamido-3-methyl) butyl-3- (cs-2-chloro-v) ? n-1-yl) -pyrrole? din-5-carboxylic acid 33A. t-butyl ester of (t) - (2R.3S.5R, 1'S) -1-f-Butoxycarbonyl-2- (1 -acetamido-3-methyl) butyl-3- (cs-2-chloro) acid vin-1-yl) -pi-r-idr-5-carboxylic acid and t-butyl ester of (±) - (2R.3S.5R, 1 'S) -1-f- Butoxycarbonyl-2- (1-acetamido) -3-met? L) but? L-3- (f / -af7s-2-chloro-v! N-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 20K but using (chloromethyl) triphenylphosphonium chloride in place of methyltriphenylphosphonium bromide. The new spot of Rf 0.73 higher (ethyl acetate) was identified as the cis isomer (yield: 38.4 mg, 40%) and the lower spot Rf 0.57 (ethyl acetate) the trans isomer (yield: 42 mg, 43%) . isomer cis 1H NMR (CDCI3): 5 7.44 (br, 1H), 6.13 (d, J = 7.5Hz, 1H), 5.32 (dd, J = 9Hz, J = 7.5Hz, 1H), 431-4 16 (m , 2H), 365 (m, 1H), 3.12 (m, 1H), 2.50 (m, 1H), 1.98 (s, 3H), 1.62 (, 1H), 1.47 (s, 9H), 1.45 (s, 9H) ), 1.30-1.07 (m, 2H), 082 (m, 6H) MS: (M + H) * = 459 / shallow trans 1H NMR (CDC) 'd 6.12-5.90 (m, 2H), 430-4.07 (, 2H), 3.64 (m, 1H), 262-237 (m, 2H), 1.98 (s, 3H), 1.69 (m, 1H), 1.48 (s, 9H), 1.45 (s, 9H), 1 26 (m, 2H), 0.91 (, 6H) MS. (M + H) * = 459 33B. Salt of acid trifluoroacetic acid (±) - (2R, 3S.5R, 1'S) -2- (1-acetamido- 3-methyl Dbuyl-3- (c / s-2-chloro-vinyl) 1 -i I) - pyrro I-1-n-5-carboxylic acid (±) - (2R, 3S, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-aceta) was reacted. ? do-3-methyl) butyl-3- (c / 's-2-chloro-vin-1-yl) -pyrrolidine-5-carboxylic acid (10 mg, 0.022 mmol) with trifluoroacetic acid (1.8 mL) in dichloromethane (0.4 L) at room temperature for 7 hours The reaction was concentrated in vacuo The residue was dried under high vacuum to give the title compound H NMR (DMSO-dβ): 8.015 (d, J = 7.63Hz) , 1H), 6.42 (d, J = 7.02Hz, 1H), 5.89 (dd, J = 7.02Hz, J = 8.7Hz, 1H), 4.42 (m, 1H), 4.17 (m, 1H), 3.59 (m , 1H), 3.31 (m, 1H), 2.47 (m, 1H), 1.88 (s, 3H), 1.84 (m, 1H), 1.58 (m, 1H), 1.39 (m, 1H), 1.29 (m, 2H), 0.885 (d, J = 6.71Hz, 3H), 0.83 (d, J = 6.41, 3H) MS- (M + H) * = 303 Example 34 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1 'S) -2- (1-acetamido-3-methyl) butyl-3- (rasp-2-chloro-v- n- 1-yl) -pyrrolidine-5-carboxylic acid 34B. Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'S) -2- (1-acetamido-3-methyl) butyl-3- (frans-2-chloro-vinyl) -pyrrolidin -5-rboxí lico. The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3- (fra / 7S-2-chloro-vin-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (+) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (c / s-2-chloro-vin-1-yl) -pyrrole i di n- 5 - carboxyl. 1 H NMR (DMSO-de): d 8.04 (d, J = 7.93Hz, 1H), 6355 (d, J = 13.1 Hz, 1H), 5.93 (dd, J = 13.1 Hz, J = 9.32 Hz, 1H), 4.33 (m, 1H), 419 (m, 1H), 2.95 (m, 1H), 2.40 (m, 1H), 1.94 (, 1H), 1.88 (s, 3H), 1 58 (m, 1H), 1.39 (m, 1H), 1.29 (m, 1H), 0.89 (d, J = 6.7 Hz, 3H), 0.825 (d, J = 6.7 Hz, 3H). MS: (M + H) * = 303 EXAMPLE 35 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-etipbutyl-3- (c; s-pro? In-1-) ip-pyrrolidine-5-carboxylic 35A. t-butyl ester of (+) - (2R, 3R, 5R, 1'S) -1-r-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic.

To a suspension of triphenylphosphonium bromide (479 mg, 1.29 mmol) in 3 mL anhydrous toluene was added potassium t-butoxide (1.0 M in THF, 0.94 mmol) by dropping at room temperature. After stirring for 2.5 hours, (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl- t-butyl ester pyrrolidine-5-carboxylic acid (90 mg, 0.211 mmol) in 5 mL of toluene was added dropwise and stirred for 1 hour. The reaction was set with saturated aqueous solution of ammonium chloride and diluted with ethyl acetate. The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound, as an oil (yield: 70.6 mg, 76%). MS: (M + H) * = 439 35B. Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (cys-propen-1-yl) -pyrrolidine-5-carboxylic acid .

The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetylated-3-methyl) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'S) t-butyl ester - 1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (cs-2-chloro-vinyl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-d 6): d 8.04 (d, J = 7.5 Hz, 1 H), 5.51 (m, 1 H), 5.26 (m, 1 H), 4.32 (m, 1 H), 4.18 (m, 1 H), 3.45 (m, 1H), 3.18 (m, 1H), 2.39 (m, 1H), 1.88 (s, 3H), 1.73 (m, 1H), 1.63 (dd, 3H), 1.58 (m, 1H), 1.38 (m, m, 1H), 1.28 (m, 1H), 0.88 (d, J = 6Hz, 3H), 0.81 (dd, J = 6Hz, 3H). MS: (M + H) * = 283 EXAMPLE 36 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'S) -2- (1-acetamido-3-met? L) but? L-3- (2,2-d? met? lv? n-1-? l) -pyrrolidone-5-carboxyl? 36A (±) - (2R.3S, 5R, 1'S) t-butyl ester -1-f-Butoxycarbonyl-2- (1 -acetamido-3-methyl I) butyl-3- (2,2-di methyl) l-vin-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 20K but using isopropyl tp-phenylphosphonium iodide instead of methyltriphenylphosphonium bromide (yield: 22.6 mg, 33%) 1 H NMR (CDCl 3) d 7.77 (d, 1 H), 506 (d, J = 10 Hz, 1 H), 4.18 (m, 2 H), 350 (m, 1H), 2.69 (m, 1H), 2.32 (m, 1H), 1.97 (s, 3H), 1.70 (s, 3H), 1.64 (s, 3H), 1.65 (m, 1H), 1.47 (s, 9H), 1.44 (s, 9H), 1.30-1.00 (m, 3H), 0.93 (d, J = 6Hz, 3H), 0.88 (d, J = 6Hz, 3H) MS- (M + H) * = 453 36B. Salt of trifluoroacetic acid acid (±) - (2R, 3S.5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (2,2-dimethyl-v? N-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3- (2,2-dimethyl-vin-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, t-butyl ester, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (c; s-2-chloro-vin-1-yl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-dβ): d 8.01 (d, J = 7.5HZ, 1H), 4.99 (d, J = 10Hz, 1H), 4.30 (m, 1H), 4.14 (m, 1H), 3.40 (m, 1H), 3.06 (m, 1H), 2.36 (m, 1H), 1.86 (s, 3H), 1.66 (s, 3H), 1.63 (s, 3H), 1.57 (m, 1H), 1.39-1.20 (m , 3H), 0.88 (d, J = 6Hz, 3H), 0.81 (d, J = 6Hz, 3H). MS: (M + H) * = 297 EXAMPLE 37 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-methyl butyl-3- (2, -dif luoro-v? N-1 -il) ) - pi rrol id in-5-carboxylic 37A. t-butyl ester of (+) - (2R.3S, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (2,2-difluoro-vinyl) acid 1-yl) -pyrrolidine-5-carboxylic acid. N-Butyllithium (1 6M in hexanes, 0.61 L, 0.97 mmol) was added to diisopropylamine (136 μL, 0.97 mmol) in 4 mL THF at -78 ° C and stirred for 30 min. Diethyl difluoromethylphosphonate (182 mg, 0.97 mmol) was added, the colorless solution slowly changed to yellow after stirring at -78 ° C for 2 hours. (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester was added. (59 mg, 0.138 mmol) in 3 mL THF, with stirring at "78 ° C for 30 min, then warmed to room temperature The mixture was then heated to reflux for 1.5 hour, and stirred at room temperature overnight The reaction was set with saturated aqueous solution of ammonium chloride, and diluted with ethyl acetate.The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound, as a yellow oil (23.4 mg, 37%). H NMR (CDCl 3): d 7.44 (d, 1H), 5.92 (ddd, 1H), 4.30-4.00 (m, 2H), 3.55 (m, 1H), 2.69 (m, 1H), 2.45 (m, 1H) , 200 (s, 3H), 1 47 (s, 9H), 1.43 (s, 9H), 1.45-1.00 (m, 4H), 0.91 (m, 6H). MS: (M + H) * = 461 37B. Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3- (2,2-difluoro-vin-1-yl) -pyrrolidine -5-carboxylic acid. The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3-methyl) butyl-3- (2,2-difluoro-vin-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, t-butyl ester, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (c / s-2-chloro-vin-1-yl) -pyrrolidine-5-carboxylic acid. H NMR (DMSO-dβ): d 8.04 (d, J = 7.5Hz, 1H), 4.59 (ddd, 1H), 4.23 (m, 1H), 4.14 (m, 1H), 3.48 (m, 1H), 3.39 (m, 1H), 2.91 (m, 1H), 2.43 (m, 1H), 1.85 (s, 3H), 1.58 (m, 1H), 1.40 (m, 1H), 1 31 (m, 1H), 1.22 (, 1H), 0.89 (d, J = 7.5Hz, 3H), 0.83 (d, J = 7.5Hz, 3H). MS: (M + H) * = 305 Example 38 Salt of trifluoroacetic acid of (±) - (2R.3R.5R.1'S) -2- (1-acetamido-3-methyl) butyl-3- (pyrazol-3-yl) -pyrrolidin-5 -carboxylic 38A. acid t-butyl ester (±) - (2R, 3R.5R, 1'S, 1"RS) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (1-hydroxy) 2-propyn-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 4A but using 2-propynyl magnesium bromide instead of ethyl magnesium bromide and using (+) - (2R, 3R, 5R, 1'S) -1- / - Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester (250 mg, 0.587 mmol) in place of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine t-butyl ester -5-carboxylic acid The crude product was used directly in the following reaction MS: (M + H) * = 453 UÉÁU & Mi 38B. acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -1-r-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (1-oxo-2-) propyn-1-yl-pyrrolidone-5-carboxylic acid (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1 -) acetam id o-3-methyl) butyl-3- (1-hydroxy-2-propyn-1-yl) -pyrrolidine-5-carboxylic acid with Jones's reagent (3.0 M in acetone, 0.33 mL) in acetone (90 mL) at 0 ° C at room temperature for 1 hour The reaction was diluted with ethyl acetate.The organic layer was washed with water, and brine, dried over MgSO 4, filtered and concentrated in vacuo.The residue was purified by chromatography silica gel using 50% ethyl acetate / hexanes to give the title compound, as a white solid (yield: 143 mg, 54%) MS: (M + H) * = 451 38C t-butyl ester of (+) - (2R.3R.5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl 3- (pyrazole) -3-yl) -pyrrole? Din-5-carboxyl? Co The (±) - (2R, 3R, 5R, 1'S) -1- 5 f-Butoxycarbon? -2- acid t-butyl ester was reacted. (1-acetamido-3-methyl) butyl-3- (1-oxo-1-et? Nyl) methyl-pyrrolidine-5-carboxylic acid (140 mg, 0.311 mmol) with hydrazine monohydrate (0.24 L, 4944 mmol) in ethanol (12 mL) at room temperature for 4 hours. The reaction was concentrated in vacuo. The residue was purified by chromatography on silica gel using ethyl acetate to give the title compound, as a white solid (yield: 131 mg , 91%). MS- (M + H) * = 465 38D Salt of the acid tpfluoroacetic acid (±) - (2R.3R, 5R.1 'S) -2- (1-acetamido-3-methyl) butyl-3- (pyrazol-3-yl) -pyrrolidine -5-carboxylic acid. The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbon t-butyl ester? 2- (1-acetamido-3-methyl) butyl-3- (pyrazol-3-yl) -pyrrolidin-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido) t-butyl ester -3-methyl) butyl-3- (c / s-2-chloro-vinyl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-dβ): 68.13 (d, J = 7.5Hz, 1H), 7.65 (d, J = 2.2Hz, 1H), 6.20 (d, J = 2.2Hz, 1H), 4.39 (m, 1H) , 4.25 (m, 1H), 3.94 (m, 1H), 3.56 (q, J = 7.5Hz, 1H), 2.62 (m, 1H), 2.17 (, 1H), 1.87 (s, 3H), 1.42 (m , 1H), 1.21 (m, 1H), 1.11 (m, 1H), 0.80 (d, J = 6.6Hz, 3H), 0.71 (d, J = 6.6Hz, 3H). MS: (M + H) * = 309 Example 39 Salt of the trifluoroacetic acid of (+) - (2R, 3R.5R.1'S) -2- (1-acetamido-3-methyl) butyl-3- (isoxazol-3-ip-pyrrolidin-5) carboxylic acid and salt of (±) - (2R, 3R, 5R.1'S) -2-f1-acetamido-3-methyl) butyl-3- (isoxazol-5-yl) -pyrrolidine-5-carboxylic acid trifluoroacetic acid. 39A. t-butyl ester of f ±) - (2R.3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1 -acetamido-3-methyl) butyl-3- (isoxazol-3-yl) -pyrrolidine-5-carboxylic acid y (t) -butyl ester (±) - (2R.3R.5R, 1'S) -1-r-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (isoxazol-5-yl) -pyrrolidine-5-carboxylic acid (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3) -butyl ester was reacted -methyl) butyl-3- (1 -oxo-1 -e ti nil) meti I- pyrrolidine-5-carboxylic acid (31 mg, 0.07 mmol) with hydroxyamine hydrochloride (4.9 mg, 0.07 mmol) and sodium carbonate (3.7 mg, 0.035 mmol) in ethanol (3 L) at reflux for 30 hours. The reaction was concentrated in vacuo. The residue was purified by chromatography on silica gel using 3% methanol / dichloromethane to give the title compound, as an oil (yield: 11.5 mg, 36%). MS: (M + H) * = 466 39B. Salt of trifluoroacetic acid of f ±) - (2R.3R, 5R.1 'S) -2-f 1 -acetam-ido-3-methyI) butyl-3- (isoxazol-3-yl) -pi rrol idin -5-carboxylic acid and trifluoroacetic acid salt of f ±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl-3- (-soxazole-5-p -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 33B, using (±) - (2R, 3, 5R, 1'S) -1 t-butyl ester -f-Butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (isoxazol-3-yl) -pyrrolidine-5-carboxylic acid and t-butyl ester of (±) - (2R, 3R) , 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (isoxazol-5-yl) -pyrrolidin-5-carboxylic acid instead of t-butyl acid ester (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (cs-2-chloro-v and I) -pir rol idin -5 -carboxilico. 1 H NMR (DMSO-d 6) - 58.91, 854 (d, 1 H), 8 12, 805 (d, J = 7.5 Hz, 1 H), 664, 6.43 (d, 1 H), 4.48, 4.51 (m, 1 H), 4.28 (m, 1H), 3.97, 3.89 (m, 1H), 3.70, 3.81 (m, 1H), 2.72 (, 1H), 220, 2.25 (m, 1H), 1.83, 1.80 (s, 3H), 1.48 (m, 1H), 1.34-1.10 (m, 2H), 0.83, 0.84 (d, J = 6Hz, 3H), 0.77, 0.78 (d, J = 6Hz, 3H) MS: (M + H) * = 310 EXAMPLE 40 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R) -2- (1-Acetamido-2-hydroxy) ethyl-3- / cs-propen-1-yl) -pyrrolidine -5-carboxylic 40A. (+) - (2R, 3R, 5R) -1-Benzyl-2-vinyl-3- (acetoxyethyl) D-pyrrolidin-5-carboxylic acid t-butyl ester (t-butyl ester of the acid was reacted ±) - (2R, 3R, 5R) -1- Benzyl-2-vinyl-3- (hydroxymethyl) -pyrrolidine-5-carboxylic acid (54.2 g, 0.17 mol) and 4- (dimethylamino) pyridine (0.5 g, 4.1 mmol), in anhydrous pyridine (400 mL) with acetic anhydride (30 mL, 0.32 mol) at 0 ° C for 1 hour, then allowed to cool to room temperature, the reaction was stirred an additional 16 hours. It was removed in vacuo at 30 ° C. The residue was partitioned between ethyl acetate (100 mL) and water (400 mL), the aqueous layer was extracted with ethyl acetate (3 x 100 mL) and the combined layers of ethyl acetate. ethyl were washed with brine, dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography using 10% ethyl acetate / hexanes to give the title compound as a colorless oil (yield - 49.6 g, 81%) H NMR (CDCU) d 7.28 (m, 4H), 7.21 (m, 1H), 5.68 (m, 1H), 5.21 (, 2H), 416 (dd, J = 6.3, 10.7 Hz, 1H), 4.10 (dd, J = 7.3, 10.7 Hz, 1H) , 3.92 (d, J = 13.7 Hz, 1H), 3.64 (d, J = 13.7 Hz, 1H), 3.52 (m, 1H), 3.50 (m, 1H), 2.33 (m, 1H), 2.26 (m, 1H), 2.02 (s, 3H), 1.62 (m, 1H), 1.45 (s, 9H). MS (M + H) * = 360. 40B. t-butyl ester of (+) - (2R.3R.5R.1'R) - and (±) - (2R.3R.5R.1'S) -1-Benzyl-2- (1,2-dihydroxy) ethyl-3-facetoxymethyl) -pyrrolidine-5-carboxylic acid. (±) - (2R, 3R, 5R) -1-benzyl-2-vinyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (-52.5 g, 0.15 mol) was reacted and 4-methylmorpholine N-oxide (547 g, 0.47 mol) in acetone (540 L) and water (60 mL) with osmium tetroxide (200 mg, 0.8 mmol). After 24 hours, the reaction was made with 10% sodium thiosulfate (250 mL) and concentrated in vacuo. The aqueous layer was extracted with ethyl acetate (3 x 300 mL) and the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel "** -'- * -" "--- ' using an elution gradient of ethyl acetate and dichloromethane to give the title compound as a viscous oil (yield: 41.2 g, 72%). H NMR (DMSO) d 7.32 (m, 3H), 7.30 (m, 1H), 7.22 (m, 1H), 4.48 (t, J = 5.4 Hz, 1H), 4.42 (d, J = 5.4 Hz, 1H) , 4.04 (m, 1H), 4.01 (m, 1H), 3.97 (m, 1H), 3.80 (d, J = 13.2 Hz, 1H), 3.78 (m, 1H), 3.43 (m, 1H), 3.39 ( m, 1H), 3.32 (m, 1H), 3.07 (t, J = 4.9 Hz, 1H), 2.48 (m, 1H), 2.19 (m, 1H), 1.99 (s, 3H), 1.57 (dt, J = 13.7, 2.0 Hz, 1H), 1.38 (s, 9H). MS (M + H) * = 394.

AcO- - HO- .O'Bu HO ^ W "'í O 40C.-t-butyl ester of acid (±) - (2R.3R, 5R.1'R) and (±) - (2R.3R.5R .1 'S) -2- (1,2-Dihydroxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (±) - (2R, 3R, 5R, 1) t-butyl ester was reacted 'R) and (±) - (2R, 3R, 5R, rS) -1-Benzyl-2- (1,2-dihydrox?) Ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (24 g, 61 mmol) in ethanol (300 mL) with ammonium formate (38.5 g, 0.61 mol) and 10% Pd / C (2 g) for 2 hours at reflux.The reaction was cooled and the catalyst was removed by filtration through Celite. The filtrate was concentrated in vacuo to give the title compound (yield: 16.7 g, 90%), 1 H NMR (DMSO) 54.56 (m, 1 H), 4.30 (m, 1 H), 4.06 (dd, J = 5.8, 10.9 Hz). , 2H), 379 (dd, J = 8.8, 10.5 Hz, 2H), 3.49 (m, 4H), 3.00 (, 1H), 2.35 (m, 1H), 2.16 (dt, J = 12.6, 8.5 Hz, 1H ), 2.01 (s, 3H), 1.52 (m, 1H), 1 40 (S, 9H) MS (M + H) * = 304 40D. acid t-butyl ester (±) - (2R.3R.5R.1'R) and (±) - (2R.3R.5R.1'S) -1-f- Butoxycarbonyl 2- (1, 2-dih? drox?) ethyl-3- (acetoxymethyl) -pyrrolidin-5-carboxylic acid. Reacted t-butyl ester of (±) - (2R, 3R, 5R, 1'R) and (±) - (2R, 3R, 5R, 1'S) -2- (1,2-Dih? Drox? ) ethyl-3- (acetox? methyl) -pyrrolidine-5-carboxylic acid (33.4 g, 0.11 mol) in methanol (250 mL) and water (50 mL) with di-f-butyl dicarbonate (33.6 g, 0.15 mol) during 48 hours at room temperature. The methanol was removed in vacuo and the residue was diluted with water (500 mL), and extracted with ethyl acetate (3 x 200 mL). The combined layers of ethyl acetate were washed with brine, dried with MgSO 4, filtered and concentrated. The residue was chromatographed on silica gel using methanol / dichloromethane to give the title compound as a white solid (yield: 32.8 g, 78%) 1 H NMR (DMSO) 5 4.80 (m, 1H), 445 (m, 1H ), 4.08 (m, 1H), 3.91 (m, 2H), 3.82 (m, 1H), 3.71 (m, 1H), 3.28 (m, 2H), 2.48 (m, 1H), 2.07 (m, 2H) , 2.01 (m, 3H), 1.39 (m, 18H). MS (M + H) * = 404. 40E (±) - (2R.3R, 5R, 1'R) and (+) - (2R.3R.5R, 1 'S) - 1-f-Butoxycarbonyl 2- (1-hydroxy) t-butyl ester -2-tr? Isoprop? Lsilylox?) Et? L-3- (acetoxy-methyl) -pi rrol id n-5-caboxylic acid. The (±) - (2R, 3R, 5R, 1'R) acid t-butyl ester was reacted and (+) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl 2- (1, 2-dihydroxy) ethyl-3- (acetoxy-methyl) -pyrrolidine-5-carboxylic acid (26.5 g, 66 mmol ) in anhydrous dimethylformamide (200 mL) with imiimidazole (8.9 g, 0.13 mol) and triisopropylsilyl chloride (19.0 g, 99 mmol) for 4 hours at room temperature. The solvent was removed under vacuum and the residue was partitioned between 300 mL of water and 150 mL of ethyl acetate. The aqueous layer was extracted with ethyl acetate (2 x 100 mL), and the combined layers of ethyl acetate were extracted with brine, dried with MgSO 4, filtered and concentrated. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give the title compound as a colorless oil (yield: 28.9 g, 79%) H NMR (CDCl 3) d 4.22 (m, 1H ), 4.04 (m, 3H), 3.87 (t, J = 2.0 Hz, 1H), 3.74 (dd, J = 4.9, 9.8 Hz, 1H), 3.58 (dd, J = 7.8, 10.2 Hz, 1H), 3.39 (bs, 1H), 2.61 (m, 2H). 2.03 (s, 3H), 1.75 (m, 1H), 1.46 (m, 18H), 1.07 (m, 18H). MS (M + H) * = 560. 40F (+ - (2R.3R.5R) -1-f-Butoxycarbonyl-2- (1-oxo-2-triisopropylsilyloxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-ac acid t-butyl ester Mico rbox.

Dimethylsulfoxide (6 mL, 85 mmol) was added slowly to a solution of oxalyl chloride (2 M) (19.3 mL, 38.6 mmol) in dry dichloromethane (70 mL) at -78 ° C. After 10 minutes, a solution of t-butyl ester of (±) - (2R, 3R, 5R, 1'R) and (±) - (2 R, 3 R, 5 R, 1'S) -1-f-bu toxy carbonyl 2- (1-hydroxy-2-triisopropyl-silyloxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (14.4 g, 26 mmol) in dry dichloromethane (75 mL) at a rate such that the temperature did not exceed -70 ° C. After 15 hours, triethylamine (18 mL, 0 13 mol) was added and the temperature was allowed to rise to 0 ° C. The reaction was set with an ammonium chloride solution, diluted with water, and extracted with dichloromethane (3 x 100 mL). The combined dichloromethane layers were extracted with brine, dried with MgSO, filtered and concentrated. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give the title compound as a colorless oil: (yield: 11 g, 77%). 1 H NMR (CDCl 3) d 4.32 (m, 6 H), 2.43 (m, 2 H), 2.04 (s 3 H), 1.78 (, 1 H), 1.48 (s, 9 H), 1.41 (s, 9 H), 1.1 (m , 21H) MS (M + H) * = 558. 40G t-butyl ester of the acid (+) - (2R.3R.5R.1'R) and (±) - (2R.3R.5R.1 'S) ~ 1-f-Butoxycarbonyl 2- (1-amino-2-tp? Sopropylsilyloxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid. (±) - (2R, 3R, 5R) -1-f- Butoxycarbonyl 2- (1-oxo-2-triisopropylsilyloxy) ethyl-3- (acetoxymethyl) -pyrrolidin-5-acid is reacted. carboxylic acid (22 g, 39 mmol) in methanol (1 L) with ammonium acetate (77 g, 1.0 mol) and sodium cyanoborohydride (24.8 g, 0.39 mol) under reflux for 2 hours. The solvent was removed in vacuo, and the residue partitioned between water (300 L) and dichloromethane (300 L). The aqueous layer was extracted with dichloromethane (2 x 100 mL) and the combined organic layers were washed with brine, dried with MgSO, filtered and concentrated to give the title compound (crude yield: 22. Og, 100%). . 40H t-butyl ester of the acid (±) - (2R.3R.5R.1'R) and (±) -f2R.3R.5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido) -2-triisopropylsilyloxy) ethyl-3- (acetoxy-thi O-pyrrolidine-5-carboxylic acid) (-y) 2-R, 3R, 5R, 1'R) -butyl ester was reacted and (±) - (2R, 3R, 5R, 1'S) -1- < -Butoxycarbonyl-2- (1-amino-2- trisopropylsilyloxy) ethyl-3- (acetoxy? methyl) -pyrrole? din-5-carboxylic acid (approx. 39 mmol) in dichloromethane (500 mL) with acetic anhydride (18 mL, 019 mol), triethylamine (27.5 mL, 020 mol) ) and dimethylaminopyridine (50 mg, 0.39 mmol) for 18 hours at room temperature. The reaction was set with a solution of ammonium chloride. The aqueous layer was extracted with dichloromethane (3 x 100 mL) and the combined organic layers were extracted with brine, dried with MgSO 4, filtered, and concentrated. The residue was chromatographed on silica gel using ethyl acetate / hexanes to give the title compound t-butyl ester of (+) - (2R, 3R, 5R, 1'R) -1-f-butoxycarbonyl 2- ( 1 -acetamido-2-triisopropylsilyloxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (9.14 g, 39%) and t-butyl ester of (±) - (2R, 3R, 5) acid , 1'S) -1-f-butoxycarbonyl 2- (1-acetamyldo-2-trii so propi I-silyloxy) ethyl-3- (acetoxymethyl) -pyrrolidine-5-carboxylic acid (9.75 g, 41%) as white solids . (±) - (2R, 3R, 5R, 1'R) 1H NMR (CDCI3) 5 7.38 (d, J = 8.3 Hz, 1H), 4.34 (m, 1H), 4.20 (dd, J = 2.4, 10.3 Hz , 1H), 409 (dd, J = 8.8, 10.2 Hz. 1H), 4.02 (dd, J = 7.3, 10.1 Hz, 1H), 3.88 (m, 1H), 3.71 (dd, J = 4.4, 10.3 Hz, 1H), 3.65 (dd, J = 7.9, 10.3 Hz, 1H), 274 (m, 1H), 260 (m, 1H), 2.04 (s, 3H), 1.98 (s, 3H), 1.69 (dt , J = 14.1, 2.5 Hz, 1H), 1.46 (s, 9H), 1.42 (s, 9H), 1.07 (m, 21H). MS (M + H) * = 601 (±) - (2R, 3R, 5R, 1'S) 1 H NMR (CDCl 3) d 6.82 (d, 1H), 4.10 (m, 4H), 3.81 (m, 3H), 2.55 (m, 2H), 1.98 (m, 7H), 1.46 (s, 9H), 1.42 (s, 9H), 1.07 (m, 21H) MS (M + H) * = 601. 40! acid t-butyl ester (±) - (2R.3R.5R.1'R) -1-f-Butoxycarbonyl 2- (1 -acetamido-2-triisopropylsilyloxy) ethyl-3-hydroxymethyl-pyrrolidine-5 -carboxylic. Reacted t-butyl ester of (±) - (2R, 3R, 5R, 1'R) -1-f-Bu toxycarbon I 2- (1-acetamido-2-triisopropylsilyloxy) ethyl-3- (acetoxy) methyl) -pyrrolidine-5-carboxylic acid (8.2 g, 13.66 mmol) in methanol (200 mL) and water (50 mL) with potassium carbonate (19 g, 136 mmol) at room temperature for 2 hr. The solvent was then removed in vacuo and the residue partitioned between water (100 mL) and dichloromethane (3 x 100 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound as a colorless oil. 40J (±) - (2R.3R, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1-acetamido-2-trisopropylsilyloxy) ethyl-3-formyl-pyrrolidin-5 acid t-butyl ester -carboxylic The title compound was prepared according to the method described in Example 2A using acid t-butyl ester (+) - (2, 3R, 5R, 1'R) -1-f-butoxycarbonyl 2- (1 -acetamido- (2-tri iso propy I-silyloxy) ethyl-3-hydroxymethyl-pyrrolidine-5-carboxylic instead of (±) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester ( yield: 5.9 g, 78%) .1H NMR (CDCU) d 1.04 -1.07 (m, 21H), 1.42 (s, 9H), 1.43 (s, 9H), 1.99 (s, 3H), 2.42 (m, 1H ), 2.62 (m, 1H), 3.04 (m, 1H), 3.69 (m, 1H), 3.82 (m, 1H), 4.08 (m, 1H), 4.38 (m, 1H), 4.57 (t, 1H) , 7.33 (br d, 1H), 9.65 (s, 1H) MS: (M + H) * = 557. 40K t-butyl ester of (±) - (2R, 3S.5R.1'R) -1-f-Butoxycarbonyl 2- (1-acetamido-2-triisopropylsilyloxy) ethyl-3- (c s-propen-1) -yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 35A using (±) - (2R, 3R, 5R, 1'R) -1-f-butoxycarbonyl 2- (1) t-butyl ester. -acetamido-2-trü sopropyl-silyloxy-) ethyl-3-formyl-pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1 'S) -1- t-butyl ester f -butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid (yield: 5.9 g, 78%). 1H NMR (CDCU) 5 1.03 -1.10 (m, 21H), 1.44 (s, 9H), 1.47 (s, 9H), 1.55 (m, 1H), 1.64 (dd, 3H), 1.96 (s, 3H), 2.55 (m, 1H), 3.42 (m, 1H), 3. 62-3.71 (m, 3H), .20 (dd, 1H), 4.30 (, 1H), 5.39 (m, 1H), 5.48 (m, 1H), 7.73 (br d, 1H) MS: (M + H ) * = 569 40L (+.) - (2R, 3S, 5R, 1'R) -1-r-Butoxycarbonyl 2- (1-acetamido-2-hydroxy) ethyl-3- (cs-propen- 1-yl) -pyrrolidine-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1-acetamido-2-triisopropylsilyloxy) ethyl-3- (cs-p? Pen-7- / 7-pyrrolidine-5-carboxylic acid (4.85 g, 8.54 mmol) in THF (100 mL) with tetrabutyl ammonium fluoride (1M in THF) (12.8 mL, 12.8 mmol) for 30 minutes at room temperature. Water (100 mL) was added followed by extraction using dichloromethane (2 x 100 mL) .These organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo.The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 2: 1 to give the title compound as a colorless solid (yield: 3.1 g, 89%) H NMR (CDCU): d 1.44 (s, 9H), 1.47 (s, 9H), 1.56 ( dd, 3H), 1.80 (m, 1H), 2.02 (s, 3H), 2.67 (m, 1H), 3.11 (t, 3H), 3.44 (dd, 1H), 3.59 (dd, 1H), 3.74-3.84 (m, 2H), 4.15 (dd, 1H) 5.39 (m, 1H), 5.58 (m, 1H), 6.42 (br d, 1H).

MS- (M + H) * = 413. 40M salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetami o-2-hydroxy) ethyl-3- (c; 's-propen-1-il ) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 33B, using acid t-butyl ester (+) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) ethyl-3-cs-propen-1-yl) -pyrrolidin-5- carboxylic acid instead of (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3- (frans-2-) t-butyl ester chloro-vinyl) -pyrrolidine-5-carboxylic acid (yield: 18.0 mg, 100%). ? NMR (DMSO-dβ): d 1.66 (dd, 3H), 1.71 (dt, 1H), 1.87 (s, 3H), 2.41 (dt, 1H), 3.18 (m, 1H), 3.43 (dd, 1H), 3.61 (m, 1H), 4.13 (m, 1H), 4.35 (m, 1H), 5.25 (m, 1H), 5.51 ( m, 1H), 8.05 (d, 1H), 9.16 (br s, 2H). MS: (M + H) * = 257.

Example 41 Sai of the acid trifluoroacetic acid (±) - (2R.3S, 5R.1'R, 2'S) -2- (1-Acetamido-2-hydroxyl) butyl-3- (c s- propen-1-? O-pyrrolidine-5-carboxylic acid 41A (-) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1-ace tamido-1-phenyl) methyl-3- (cs-pro) acid t-butyl ester pen-1-yl) -pyridine-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'R) -1-f- Butoxycarbonyl 2- (1-acetamido-2-hydroxy) ethyl-3- (c / ') acid was reacted. s-propen-1-yl) -pyrrolidine-5-carboxylic acid (600 mg, 1.46 mmol) in dichloromethane (50 mL) with Dess-Martin Periodinane (928 mg, 2.18 mmol) for 1 hour at room temperature. The reaction was set with 1M aqueous sodium thiosulfate solution (50 mL), stirred for 20 minutes then extracted with dichloromethane (3 x 100 mL). The organic cap was dried over magnesium sulfate, concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2/1: ethyl acetate / hexane to give the title compound (yield: 547 mg, 92%). 1H NMR (CDCU) d 9.40 (d, J = 1 Hz, 1H), 7.88 (bd), 5.69 (m, 1H), 527 (m, 1H), 4.78 (dd, J = 9.5, 1. Hz, 1H ), 4.21 (t, J = 8. Hz, 1H), 3.45 (m, 2H), 2.41 (m, 1H), 2.09 (s, 3H), 1.69 (dd, J = 7.0, 1. Hz, 3H) , 1.55 (m, 1H), 1.46 (s, 9H), 1 40 (s, 9H).

MS: (M + H) * = 411, (M-H) - = 409. 41B t-butyl ester of (+) - (2R, 3S.5R.1'R.2'R) and (± - (2R.3S, 5R.1, R, 2, S) -1-f- Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cis-pro pe n-1-yl) -pyrrolidone-5-carboxylic acid. acid ester (±) - (2R, 3S, 5R, 1'R) -1-f- Butoxycarbonyl 2- (1 -acetamido-1-f ormyl) methyl-3- (c; s-propen-1) -yl) -pyrrolidine-5-carboxylic acid (780 mg, 1.90 mmol) in THF (20 mL) to a solution of ethylmagnesium bromide (3M in ether) (3.17 mL, 9.51 mmol) in THF (15 L) at room temperature and it was reacted for 40 minutes.The reaction was set with water (20 mL) and saturated aqueous solution of ammonium chloride (20 mL) followed by extraction using dichloromethane (3 x 50 L) .The organic layer was dried over sodium sulfate. magnesium, filtered and concentrated in vacuo The residue was purified by column chromatography on silica gel using 2/1: ethyl acetate / hexane to give the title compounds t-butyl ester of (±) - (2R) acid. , 3S, 5R, 1'R, 2'R) -1-f-butoxica rbonyl 2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 472 mg, 56%) and t-butyl ester of the acid ( ±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl 2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic acid (yield: 82 mg, 10%) as a colorless oil. (±) - (2R, 3S, 5R, 1'R, 2'R) = MS: (M + H) * = 441, (M + Na) + = 463, (M-H) - = 439. (±) - (2R, 3S, 5R, 1'R, 2'S) = MS: (M + H) * = 441, (M + Na) + = 463, (M-H) - = 439. 41C salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetam ido-2-hydroxy) bu ti l-3- (c) 's-propen -1-yl) -pyrrolidine-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-Butoxycarbonyl-2- (1-acetam) -butyl ester was reacted α-dodo-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (300 mg, 0.68 mmol) with trifluoroacetic acid (8 mL) in dichloromethane (2 mL) at room temperature during 6 hrs The reaction was concentrated in vacuo overnight to give the title compound (yield: 311 mg) as a colorless solid. 1 H NMR (500 MHz, DMSO-d 6) d 7.89 (d, J-8.7 Hz, 1 H), 5.48 (m, 1 H), 5.29 (m, 1 H), 4.30 (m, 1 H), 4.02 (m, 1 H) , 3.73 (m, 1H), 3.43 (m, 1H), 3.15 (m, 1H), 2.41 (m, 1H), 1.82 (s, 3H), 1.63 (m, 1H), 1.59 (dd, J = 6.8 , 1.9 Hz, 3H), 1.55 (m, 1H), 1.27 (m, 1H), 0.85 (t, J = 7.3 Hz, 3H). MS: (M + H) * = 285, (M + Na) * = 307, (M-H) "= 283.

EXAMPLE 42 Salt of tpfluoroacetic acid of (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetam-do-2-hydroxy) butyl-3- (c s-propen -1-? L) -pyrrole-din-5-carboxylic acid 42A (±) - (2R, 3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-oxo) butyl-3- (c / s-propen) acid ester -1-yl) -pyrrolidine-5-carboxylic acid. (±) - (2R, 3S, 5R, 1'R, 2'R) -1 - / - Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3 acid was reacted. - (c / s-propen-1-yl) -pyrrol? d? n-5-carboxyl? co (460 mg, 1.05 mmol) with Dess-Martin Periodinane (666 mg, 1.57 mmol) in dichloromethane (30 mL) at room temperature for 17 hours. The reaction was fired with 1M aqueous sodium thiosulfate solution (50 mL and stirred for 20 min.) The reaction was extracted with dichloromethane (3 × 100 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2: 1: ethyl acetate / hexane to give the title compound as a colorless semi-solid (yield: 440 mg, 96%). MS: (M + H) * = 439, (M + Na) + = 461, (M-H) - = 437. 42B t-butyl ester of the acid (±) - (2R, 3S.5R.1'R.2'R) and (±) - (2R.3S.5R, 1'R, 2'S) -1-f-Butoxycarbon ? l-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxyl? co. The (±) - (2R, 3S, 5R, 1'R) -1-t-Bu toxycarbonyl-2- (1 -acetamido-2-oxo) bu ti l- (t) -butyl ester was reacted 3- (c / 's- pro pen-1-yl) -pyrrolidine-5-carboxylic acid (435 mg, 0.99 mmol) in methanol (30 mL) with sodium borohydride (188 mg, 4.97 mmol) at room temperature for 0.5 hours. The solvent was removed in vacuo and water (30 mL) was added. The aqueous layer was extracted with dichloromethane (3 x 50 mL). This organic layer was dried over magnesium sulfate, it was filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2: 1 ethyl acetate / hexane to give the title compounds t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-F-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidin-5-caboxylic acid. (yield: 305 mg, 70%) and t-butyl ester compounds of the (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-bu toxicarbonyl-2- (1 -aceta) mido-2-hydroxy) butyl-3- (c / 's- pro pen- 1 -i I) -pyrrolidine-5-carboxylic acid (yield: 17 mg, 4%). 42C salt of the acid trifluoroacetic acid (±) - (2R, 3S.5R, 1'R.2'S) -2- (1- Acetate mido-2-h id roxi) buti l-3- (cs- ro pen- 1 -il) -p? In-5-carboxylic acid hydrolyzate (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) -butyl ester was reacted ) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (300 mg, 0.68 mmol) with trifluoroacetic acid (8 mL) in dichloromethane (2 mL) at room temperature for 6 hrs. The reaction was concentrated in vacuo overnight and triturated with acetonitrile (2 x 5 mL) to give the title compound (yield: 311 mg) as a colorless solid. 1 H NMR (500 MHz, DMSO-d 6) D: 7.89 (d, J = 8.7 Hz, 1 H), 5.48 (m, 1 H), 5.29 (m, 1 H), 4.30 (m, 1 H), 4.02 (m, 1 H) ), 3.73 (m, 1H), 3.43 (m, 1H), 3.15 (m, 1H), 2.41 (m, 1H), 1.82 (s, 3H), 1.63 (, 1H), 1.59 (dd, J = 6.8 , 1.9 Hz, 3H), 1.55 (m, 1H), 1.27 (m, 1H), 0.85 (t, J - 7.3 Hz, 3H). MS: (M + H) * = 285, (M + Na) + = 307, (M-H) - = 283.

Example 43 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R, 2'R) -2- (1-Acetamido-2-hydroxyl) butyl-3- (cs-propen-1) -yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (+) - (2 R, 3S, 5 R, 1'R, 2'R) -1- t-butyl ester f-bu toxi carboni l-2- (1 -acetam ido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidin-5- carboxylic (yield: .0065 g, 100%). 1H NMR (DMSO-de) d 7.90 (d, J = 8.8Hz, 1H), 5.47 (m, 1H), 5.29 (t, J = 9.8 Hz, 1H), 4.29 (t, J = 8.8Hz, 1H) , 4.02 (q, J = 6.8Hz, 1H), 3.71 (bt, J = 8Hz, 1H), 3.43 (m, 1H), 3.15 (quint., J = 8.8Hz, 1H), 2.41 (dt, J = 12.7.7.8Hz, 1H), 1.82 (s, 3H), 1.64 (m, 1H), 1.58 (dd, J = 6.8.1.5Hz, 3H), 1.53 (m, 1H), 0.85 (t, J = 7.3 Hz, 3H). MS: (M + H) * = 285, (M + Na) + = 307, (M-H) "= 283, (M + CF3COOH) - = 397, (2M-1)" = 563 Example 44 Salt of trifluoroacetic acid of (+) - (2R, 3S.5R.1'R, 2'S) -2- (1-Acetamido-2-hydroxy-3-cyano-propyl-3- (cs-propen-1) -yl) -pyrrolidin-5-carboxylic acid 44A (±) - (2R.3S, 5R.1 'R.2'R) JL f2R, 3S.5R.1'R.2'S) -1-f-Butoxycarbonyl-2- (1) acid t-butyl ester -acetamido-2-hydroxy-3-cyano) propyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid. 10 (+) - (2R, 3S, 5R, 1'R) -1- f- Butoxycarbonyl 2- (1 -acetamido- 1 -f ormyl) methyl-3- (c) is added dropwise.; 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (150 mg, 0.37 mmol) in THF (10 mL) was added to a solution of the lithium enolate of acetonitrile (1.83 mmol, 5 equivalents) in THF (15 mL ) at -78 ° C and reacted for 15 minutes. The reaction was set up with saturated aqueous solution of ammonium chloride (10 mL) and water (10 mL) followed by extraction using dichloromethane (2 X 50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2/1: Ethyl acetate / hexane to give the title compounds t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl 2- (1-acetamido) 2-hydroxy-3-cyano) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 95 mg, 58%) and t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbon? 2- (1-Acetamido-2-hydrox? -3-cyano) propyl-3- (c s-propen-1-yl) ) -pyrrolidone-5-carboxylic acid (yield 30 mg, 18%) as a colorless oils. (±) - (2R, 3S, 5R, 1'R, 2'R) = MS: (M + H) * = 452, (MH) "= 450 (±) - (2R, 3S, 5R, 1 ' R, 2'S) = 1H NMR (CDCU) d 8.14 (d, J = 8.9Hz, 1H), 5.51 (m, 1H), 5.38 (m, 1H), 4.25 (m, 1H), 4.19 (m, 1H) , 3.94 (m, 1H), 3.74 (m, 1H), 3.22 (, 1H), 2.54 (m, 1H), 2.47 (m, 2H), 2.04 (s, 3H), 1.69 (m, 1H), 1.65 (dd, J = 6.5, 1.8Hz, 3H), 1.47 (s, 9H), 1.45 (s, 9H) MS: (M + H) * = 452, (MH) "= 450 44B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetate mido-2-h id roxi-3-cyano) propyl-3- (cs- propen-1-yl) -pyrrolidone-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of (±) - (2 R, 3S, 5R, 1"R, 2'S) -1-f-bu toxy carboni l-2- (1 -acetam id o-2-hydroxy-3) -cyano) propyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester -1 -f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 4.5 mg, 95 %%) .H NMR (DMSO-de) d 7.98 (d, J = 10.0 Hz, 1H), 5.49 (m, 1H), 5.27 (m, 1H), 430 (, 1H), 4.15 (m, 1H), 3.75 (m, 1H) ), 3.18 (, 1H), 2.72-2.58 (m, 2H), 241 (m, 1H), 1 85 (s, 3H), 1.65 (m, 1H), 1 61 (dd, J = 670, 1.80 Hz, 3H) MS: (M + H) * = 296, (MH) "= 294 EXAMPLE 45 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-3-cyano) propyl-3- ( c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy? -3-cyano) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (± ) - (2R, 3S, 5R, 1'R, 2'S) -1 - / - butoxycarbonyl-2- (1-acetam i do-2-h id roxi) butyl-3- (c s-propen-1 -il) ) -pyrrolidin-5-carboxylic acid (yield: 8 mg, 95%). 1 H NMR (DMSO-d 6) d 7.75 (d, J = 9.0 Hz, 1 H), 5.47 (m, 1 H), 5.25 (m, 1 H), 4.46 (m, 1 H), 4.20 (m, 1 H), 4.13 ( m, 1H), 3.56 (m, 1H), 3.15 (m, 1H), 2.55 (m, 2H), 2.42 (m, 1H), 1.82 (s, 3H), 1.72 (m, 1H), 1.55 (dd , J = 6.71, 1.83, 3H) MS: (M + H) * = 296, (M + 23) * = 318, (MH) '= 294 EXAMPLE 46 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R.2'R) -2- (1-Acetamido-2-hydroxy-3-ethoxycarbonyl) propyl-3- (c / s-propen-1-iD-? irrolidin-5-carboxyl 46A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'R) and (+.) - (2R.3S.5R. 1'R.2'S) -1-f- Toxic bu rbonyl-2- (1-a-tamido-2-hydroxy-3-e toxy carbonyl) propyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid. 10 (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-1-formyl) methyl-3- (c) acid was added dropwise. / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (900 mg, 2187 mmol) in THF (40 mL) was added to a solution of the lithium enolate in ethyl acetate (8.75 mmol, 4 equivalents) in THF (40 g). mL) at -78 ° C and reacted for 15 minutes. The reaction was set with saturated aqueous solution of ammonium chloride followed by extraction using dichloromethane (3X). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 1: 1 ethyl acetate / hexane to give the title compounds t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) 3- ethoxycarbonyl) propyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 690 mg, 63%) and t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R 2'S) -1 - / - butox? Carbon? L-2- (1 -acetam? Do-2-hydrox? -3-ethoxy? Carbon?) Prop? L -3- (c / s-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co (yield 246 mg 22 5%) (±) - (2R, 3S, 5R, 1'R, 2'R) 1H NMR (CDCU) d 599 (d, 1H), 560 (m, 1H), 536 (m, 1H), 481 (m, 1H), 415 (m 4H), 374 ( m, 1H), 307 (m, 1H), 268 (m, 1 H), 248 (m 1 H), 233 (m, 1 H), 203 (s, 3 H), 154 (dd, 3 H), 147 (s, 9H), 146 (s, 9H), 124 (t, J = 75Hz, 3H) MS (M + H) * = 499 (±) - (2R, 3S, 5R, 1'R, 2'S) 1H NMR (CDCU) d 793 (d, 1H), 544 (m, 2H), 419 (m, 4H), 403 (m, 1H), 372 (m, 1H), 337 (m, 1H), 263 ( m 1H), 248 (m, 2H), 201 (s, 3H), 165 (dd, 3H), 148 (s, 9H), 146 (s, 9H), 126 (t, J = 75Hz, 3H) MS (M + H ) * = 499 46B acid trifluoroacetic acid salt (±) - (2R.3S, 5R.1'R.2'R) -2- (1-A ketamido-2-h? D rox? -3-etox? Carb) on?) prop? l-3- (os-pro pen-1-? l) -p? rrol? d? n-5-carboxyl? co The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbon? l-2- (1-acetamido- 2-h? Drox? -3-ethoxy? Carbon? L) prop? L-3- (c / s-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co in place of acid t-butyl ester (±) - (2R 3S, 5R, 1'R 2'S) -1-f- bu toxicity rbon i l-2- (1 -acetam ido-2-h id roxi) buti l-3- (cs-propen-1-yl) -pyrrolidine-5-carboxyl? co. 1 H NMR (DMSO-de) - d 774 (d, J = 9 Hz, 1 H), 5.48 (m, 1 H), 5.25 (m, 1 H), 4.43 (m, 1 H), 424 (m, 1 H), 414 ( m, 1H), 4.06 (q, J = 7.5Hz, 2H), 3.54 (m, 1H), 3.16 (m, 1H), 2.41 (, 1H), 2.36 (m, 2H), 1.82 (s, 3H) , 1.77 (m, 1H), 1.56 (dd, 3H), 1.18 (t, J = 7.5Hz, 3H). MS: (M + H) * = 343 Example 47 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy-3-ethoxycarbonyl) propyl-3- (cs-propen-1- il) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-ethoxycarbonyl) t-butyl ester -3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester -1-f- butoxicarboni l-2- (1 -acetam ido-2-hidroxy) butyl-3- (cs-propen-1 -i I) -pyrrolidine-5-carboxylic acid. ] H NMR (DMSO-de) - d 7.93 (d, J = 9Hz, 1H), 5.48 (m, 1H), 530 (m, 1H), 4 19 (m, 1H), 4.09 (m, 1H), 4.06 (q, J = 7.5Hz, 2H), 3.94 (m, 1H), ^ j ^ é 373 (m, 1H), 3.18 (m, 1H), 254 (dd, 1H), 240 (m, 1H), 2.27 (m, 1H) 1.82 (s, 3H), 1.65 (m, 1H), 1 60 (dd, 3H), 1.19 (t, J = 7.5Hz, 3H). MS: (M + H) * = 343 Example 48 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy) propyl-3- (c; s-? Ropen-1-? l) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2, S) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R) t-butyl ester. 3S, 5R, 1'R, 2'S) -1 - / - butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrroli-5-carboxylic acid (yield : 0.0030 g, 100%) 1H NMR (DMSO-de) d 8.97 (bs, 1H), 7.88 (d, J = 8.5 Hz, 1H), 5.45 (m, 1H), 5.28 (t, J = 9.1Hz, 1H), 4.30 (t, J = 8.6Hz, 1H), 3.94 (q, J = 7.3Hz, 1H), 3.71 (t, J = 8.0Hz, 1H), 3.62 (m, 1H), 315 (quint. , J = 9.0Hz, 1H), 2.40 (dt, J = 12.8, 7.6Hz, 1H), 1.83 (s, 3H), 1.65 (m, 1H), 1.59 (dd, J = 7.0, 1.5Hz, 3H) , 1.08 (d, J = 5.5Hz, 3H). MS (M + H) * = 271, (M + Na) + = 293, (M-H) "= 269 Example 49 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R) -2- (1-Acetate mido-2-hydroxy) propyl-3- (cs-propen-1 -i h-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) ethyl-3- (c / 's-propen-1) -yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R.3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2) t-butyl ester -hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0143 g, 100%). 1 H NMR (DMSO-dβ) d 7.70 (d, J = 9.1 Hz, 1H), 5.49 (m, 1H), 5.25 (t, J = 9.1Hz, 1H), 4.43 (t, J = 8.6Hz, 1H), 4.03 (m, 1H), 3.92 (m, 1H), 3.55 (t, J = 8.5Hz, 1H), 3.17 (quint .. J = 8.5Hz, 1H), 2.42 (dt, J = 12.8.7.3Hz, 1H), 1.85 (s, 3H), 1.72 (dt, J = 12.8,10.0Hz, 1H), 1.57 (dd, J = 6.7.1.8Hz, 3H), 1.04 (d, J = 6.1Hz, 3H). MS: (M + H) * = 271, (M + Na) * = 293, (M-H) "= 269 Example 50 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R, 2'S) -2- (1-Acetamido-2-hydroxy-2-vinyl) ethyl-3- (c) S -propen-1-yl) -pyrrolidine-5-carboxylic acid. 50A (±) - (2R, 3S, 5R, 1 'R, 2'S) t-butyl ester and (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidin-5- carboxylic The title compounds were prepared according to the method described in Example 41B, but using vinyl magnesium bromide instead of ethyl magnesium bromide to give (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) ethyl-3- (cs-propen-1-yl) -? Irrolidin-5- carboxylic (yield: 6.5 mg, 18%) and t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido) 2-hydroxy) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 22 mg, 59%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 439, (MH) "= 437 (±) - (2R, 3S, 5R, 1'R, 2 'R) MS: (M + H) * = 439, (MH)' = 437 50B salt of acid trifluoroacetic acid (±) - (2R, 3S.5R, 1'R.2'S) -2- (1- Acetate mido-2-h id roxi-2-vi nil) ethyl-3- (cs -propen-1 -i D-pyrrolid i-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, t-butyl ester, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) ethyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid in Place of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 5 mg, 96%). 1 H NMR (DMSO-dβ) d7.85 (d, J = 9.1Hz, 1H), 5.76 (m, 1H), 5.47 (m, 1H), 5.25 (m, 2H), 5.14 (m, 1H), 4.29 (m, 1H), 4.05 (m, 1H), 3.96 (m, 1H), 3.71 (m, 1H) ), 3.18 (m, 1H), 2.41 (m, 1H), 1.78 (S, 3H), 1.64 (m, 1H), 1.59 (dd, J = 6.71, 1.21Hz, 3H) MS: (M + H) * = 283, (M + 23) * = 305, (MH) "= 281 Example 51 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'R) -2- (1-Acetamido-2-hydroxy-2-vinyl) ethyl-3- (c s-propen -1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) ethyl-3- (c s-pro ? en-1-yl) -? oleyl-din-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester-1-f-butoxycarbonyl-2 - (1-acetamido-2-hydroxy) butyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 6 mg, 95%). 1 H NMR (DMSO-de) d 7.84 (d, J = 9.7 Hz, 1 H), 5.78 (m, 1 H), 5.48 (m, 1 H), 523 (m, 34.43 (m, 1 H), 4.26 (m, 1 H) ), 4.20 (, 1H), 3.55 (m, 1H), 3.18 (m, 1H), 2.43 (m, 1H), 1.81 (s, 3H), 1.73 (m, 1H), 1.57 (dd, J = 6.72, 1.83 HZ, 3H) MS: (M + H) * = 283, (M + 23) "= 305, (M-H) '= 281, (2M-H)' = 563 Example 52 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-hydroxy-2-vinyl) propyl-3- (c s-propen -1-yl) -pyrrolidine-5-carboxylic acid. 52A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester v (±) - (2R, 3S.5R. 1'R.2lR) -1-f-Butoxycarbonyl-2 - (1-acetamido-2-hydroxy-3-vinyl) propyl-3- (cis-gold pen-1-yl) -pyrrole id in-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, but using allyl magnesium bromide in place of ethyl magnesium bromide to give (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) propyl-3- (c / s-propen-1-yl) -pyrrolidin-5 -carboxylic (yield: 2.0 mg, 5%) and t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1) -acetamido-2-hydroxy) propyl-3- (cs-pro pen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 9.0 mg, 22%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 453; (MH) "= 451. (±) - (2R, 3S, 5R, 1, R, 2, R) 1H NMR (DMSO-d6) d 7.70 (d, J = 9.3Hz, 1H), 5.80 (m, 1H), 5.51 (m, 1H), 5.30 (m, 1H), 5.00 (m, 2H), 4.58 (br d, 1H), 3.93 (m, 2H), 3.50 (m, 1H), 3.22 (br t , 1H), 2.02 (m, 3H), 1.88 (s, 3H), 1.56 (m, 4H), 1.41 (s, 9H), 1.36 (s, 9H) MS- (M-H) - = 451, (M + H) * = 452, (M + Na) * = 475 52B salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-hydroxy-3-vinyl) propyl-3- (cs-propen -1-yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (+) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-vinyl) propyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-) t-butyl ester acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2 mg, 100%). 1 H NMR (DMSO-de) d 7.85 (d, J = 9.3 Hz, 1 H), 5.81 (m, 1 H), 5.42 (m, 1 H), 5.28 (t, J = 7.3 Hz, 1 H), 5.01 (br d , 2H), 3.99 (m, 2H), 3.57 (m, 2H), 3.08 (m, 1H), 2.33 (m, 1H), 2.26 (m, 1H), 2.07 (m, 1H), 1.81 (s, 3H), 1.57 (dd, J = 1.4, 5.4Hz, 4H) MS: (M-H) - = 295; (M + H) * = 297, (M + Na) * = 319.

Example 53 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R) -2- (1-Acetamido-2-hydroxy-3-vinyl) propyl-3- (c s-propen -1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-vinyl) propyl-3- (c / s- propen-1-yl) -pyrrolidin-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (t) butyl ester ( 1-acetamido-2-hydroxy) butyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 6 mg, 100%). 'H NMR (DMSO-dβ) d 7.68 (d, J = 9.2Hz, 1H), 5.78 (m, 1H), 5.48 (m, 1H), 5.24 (t, J = 7.8Hz, 1H), 5.04 (m , 2H), 4.38 (t, J = 7.0, 1H), 4.09 (t, J = 7.0, 1H), 3.81 (t, J = 4.7, 1H), 3.53 (t, J = 8.5, 1H), 3.16 (m, 1H), 2. 40 (m, 1H), 2.11 (m, 2H), 1.83 (s, 3H), 1.70 (m, 1H), 1.55 (dd, J = 5.4, 1.4Hz, 3H) MS: (M-H) - = 295; (M + H) * = 297, (M + Na) * = 319.

Example 54 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy) pentyl-3-fc / s-pro? En-1 -yl) -pyrrolidine-5-carboxylic acid. 54A (±) - (2R, 3S.5R, 1'R.2'S) t-butyl ester V (±) - (2R.3S.5R.1 'R.2' R) - 1-f-Butoxycarbonyl -2- (1 -acetamido-2-hydroxy) penyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, but using propyl magnesium bromide instead of ethyl magnesium bromide to give (+) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pentyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 1 mg , 1%) and t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pentyl- 3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 32 mg, 39%). (±) - (2R, 3S, 5R, 1'R, 2'S) 'HNMR (CDCU) 5 7.51 (d, J = 8.2Hz, 1H), 5.46 (m, 2H), 4.17 (dd, J = 3.1, 6.8Hz, 1H), 4.05 (m, 1H) 3.81 (t, J = 3.4Hz, 1H), 3.54 (m, 1H), 3.21 (m, 1H), 2.60 (m, 1H), 2.02 (s, 3H) ), 1.70 (dt, J = 3.0, 7.4Hz, 1H), 1.61 (d, J = 5.4Hz, 3H), 1.54 (m, 1H), 1.47 (s, 9H), 1.44 (s, 9H), 1.32 (m, 4H), 0.90 (t, J = 7.1Hz, 3H) MS: (M + H) * = 455, (M + Na) * = 477; (M-H) "= 453. (±) - (2R, 3S, 5R, 1'R, 2'R) 1H NMR (CDCU) d 5.98 (d, J = 9.5Hz, 1H), 560 (t, J = 9.8Hz, 1H), 536 (m, 1H), 4 16 (m, 1H), 3.75 (d, J = 10 1Hz, 1H), 3.64 (m, 1H), 3.51 (m, 1H), 3.09 (br t, 1H), 2.68 (m, 1H), 2.02 (s, 3H), 1.81 (d, J = 13.9Hz, 1H), 1.57 (m, 4H), 1.54 (dd, J = 1.7, 5.1Hz, 3H), 1.46 (s, 9H), 1.45 (s, 9H), 0.88 (t, J = 6.8Hz, 3H) MS: (MH) - = 453; (M + H) * = 455. 54B salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy) pentyl-3- (c? S-propen-1-yl) ) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) pentyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cys-propen-1-yl) -pyrrolidin-5- carboxylic (yield: 1 mg, 100%). H NMR (DMSO-dβ) d 7.83 (d, J = 9.2Hz, 1H), 5.43 (m, 1H), 5.23 (m, 1H), 3.98 (m, 1H), 3.56 (br t, 1H), 3.46 (m, 1H), 3.08 (m, 2H), 2.32 (m, 1H), 1.80 (s, 3H), 1.57 (d, J = 1.4, 5. Hz, H), 1.43 (m, 2H), 1.23 (m, 2H), 0.85 (br t, 3H) MS. (M + H) * = 299, (M + Na) * = 321.

Example 55 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R) -2- (1-Acetam-do-2-hydroxy) pentyl-3- (cs-? Ropen-1) -yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R) t-butyl ester , 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl acid ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-r-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1) -yl) -pyrrolidine-5-carboxylic acid (yield: 0.0190 g, 100%). ? NMR (DMSO-dβ) d 7.64 (d, J = 9.3Hz, 1H), 5.48 (m, 1H), 5.24 (m, 1H), 4.38 (t, J = 8.8Hz, 1H), 4.06 (m, 1H) ), 3.75 (m, 1H), 3.53 (t, J = 8.5Hz, 1H), 3.16 (quint., J = 8.5Hz, 1H), 2.41 (dt, J = 12.8.7.3Hz, 1H), 1.82 ( s, 3H), 1.70 (dt, 12.8.9.9Hz, 1H), 1.55 (dd, J = 7.0.1.6Hz, 3H), 1.35 (, 2H), 1.26 (m 2H), 0.86 (t, J = 6.7 Hz, 3H). MS: (M + H) * = 299, (M + Na) * = 321, (M-H) "= 297.

Example 56 Salt of the acid tpfluoroacetic acid (±) - (2R.3S.5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy-3-methyl) but? L-3- ( c / s-propen-1-yl) -pyrrole-din-5-carboxylic acid. 56A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester v (±) - (2R.3S.5R. 1'R, 2'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) butyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid . The title compounds were prepared according to the method described in Example 41B, but using propyl magnesium isobromide in place of ethyl magnesium bromide to give (±) - (2R) t-butyl ester, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) butyl-3- (c / s-propen-1-15 yl) - pyrrolidine-5-carboxylic acid (yield: 0.0092 g, 10%) and t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- ( 1- acetamido-2-hydroxy-3-methyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0385 g, 40%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 455, (M + Na) * = 477, (2M + Na) * = 20 931, (MH) = 453. (±) - (2R, 3S, 5R, rR, 2'R) MS: (M + H) * = 455, (M + Na) * = 477, (2M + Na) * = 931, (M-H) - = 453. 56B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy-3-methyl) butyl-3- (cs-propen-1) -yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2 R, 3S, 5 R, 1 't-butyl ester. R, 2'S) - 1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy-3-methyl) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t -butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1) -yl) -pyrrolidine-5-carboxylic acid (yield: 0.010 g, 100%). 1 H NMR (DMSO-dβ) d 7.63 (d, J = 9.2Hz, 1H), 5.48 (m, 1H), 5.23 (m, 1H), 4.44 (m, 1H), 4.24 (m, 1H), 357 ( t, J = 8.7Hz, 1H), 3.33 (dd, J = 8.5.2.5Hz, 1H), 3.21 (quint., J = 9.1Hz, 1H), 2.43 (dt, J = 12.8.7.6Hz, 1H) , 1.81 (s, 3H), 1.73 (dt, J = 12.8.10.4Hz, 1H), 1.56 (dd, J = 6.7.1.9Hz, 3H), 1.55 (m, 1H), 0.94 (d, J = 6.7 Hz, 3H), 0.78 (d, J = 6.7Hz, 3H). MS: (M + H) * = 299, (M + Na) * = 321, (M-H) "= 297, (M + CF 3 COOH) - = 411, (2M-H)" = 595.

Example 57 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-3-methyl) butyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) butyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-) acetamido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0433 g, 100%). 1H NMR (DMSO-d6) d 7.88 (d, J = 9.2Hz, 1H), 5.46 (m, 1H), 5.29 (m, 1H), 4.26 (t, J = 8.5Hz, 1H), 4.11 (m, 1H), 3.67 (m, 1H), 3.39 (dd, J = 9.8.1.8Hz, 1H), 3.15 (quint., J = 9.1Hz, 1H), 2.42 (dt, J = 12.8.7.9Hz, 1H), 1.81 (s, 3H), 1.73 (m, 1H), 1 62 (m, 1H), 1.57 (dd, J = 7.0.1.6Hz, 3H), 0.88 (d, J = 6.7Hz, 3H), 0.75 (d, J = 6.7Hz, 3H). MS: (M + H) * = 299, (M + Na) * = 321, (M-H20) * = 281, (MH) "= 297, (M + CF3COOH) - = 411, (2M-H) "= 595 Example 58 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'S -2- (1-Acetamido-2-hydroxy) hex? L-3- (cs-propen- 1-? L) -pyrrole-in-5-carboxylic acid. 58A (±) - (2R.3S.5R.1'R, 2'S) t-butyl ester v (±) - (2 R.3S.5 R.1'R.2 'R) - 1-f - Bu toxi carbo ni l-2- (1 -acetamido-2-hydroxy) hexy I-3- (c s-? Ropen-1-yl) -pyrrolidin-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, but using butyl magnesium bromide in place of ethyl magnesium bromide to give (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) hex? L-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.0 mg, 8%) and t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) hexyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 6.0 mg, 24%) ugly ... 58B salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R, 2'S -2- (1-Acetamido-2-hydrox?) Hexyl-3- (c; s-propen-1-il ) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, t-butyl ester, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) hexyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.0 mg, 100%). 1H NMR (DMSO-de) d 8.34 (d, J = 9.3Hz, 1H), 5.24 (m, 1H), 5.12 (m, 1H ), 3.90 (m, 1H), 3.78 (m, 1H), 3.23 (, 1H), 2.90 (m, 1H), 2.14 (m, 1H), 1.80 (m, 1H), 1.75 (s, 3H), 1.52 (m, 3H), 1.45 (m, 1H), 1.08 (br s, 6H), 0.83 (br t, 3H) MS: (MH) - = 311; (M + H) * = 313.

Example 59 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R.2'R) -2- (1-Acetamido-2-hydroxy) hexyl-3- (cjs-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2 R, 3S, 5R, 1'R, 2 'R) -1-r-butoxycarbon? L-2- (1 -acetam id o-2-hidroxy) hexyl-3- (c / s-propen-1-yl) -? -rololidin-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl- t-butyl ester 2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 6.0 mg, 100%). 1 H NMR (DMSO-de) - 7.60 (d, J = 9.3 Hz, 1H), 5.46 (m, 1H), 5.24 (t, J = 9.2 Hz, 1H), 4.21 (t, J = 8.3 Hz, 1H), 4.02 (t, J = 7.9Hz, 1H), 3.74 (m, 1H), 3.47 (t, J = 88, 1H), 3.12 (m, 1H), 2.37 (m, 1H), 1.81 (s, 3H), 1. 64 (m, 1H), 1.55 (dd, J = 1.5, 5.4 Hz, 3H), 1.29 (m, 6H), 0.86 (t, J = 6.9, 3H) MS: (M-H) - = 311; (M + H) * = 313, (M + Na) * = 335.

EXAMPLE 60 Salt of the acid tpfluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1- Acetamido-2-hydrox- 4-methyl) pentyl-3- (c) s-propen-1-yl) -pyrrole-din-5-carboxylic acid. 60A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'R) -1-f- Bu toxic rbon ¡I-2-Í1 -acetam ido-2-h id rox¡ -4-methyl) pen ti l-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, but using butyl magnesium isobromide in place of ethyl magnesium bromide to give (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-methyl) pentyl-3- (c / s-propen-1-1) -p? R-rolidin-5-carboxylic acid (yield: 31 mg, 51%). (±) - (2R, 3S, 5R, 1'R, 2'R) H NMR (CDCU) 5.98 (d, J = 9.5Hz, 1H), 5.61 (t, J = 8.2Hz, 1H), 5.35 ( m, 1H), 4.51 (dd, J = 1.3, 3.1Hz, 1H), 4.15 (m, 1H), 3.74 (d, J = 10.5Hz, 1H), 3.61 (, 2H), 3.09 (t, J = 7.5Hz, 1H), 2.71 (m, 1H), 2.02 (s, 3H), 1.81 (d, J = 13.9Hz, 1H), 1.58 (br s, 1H), 1.54 (dd, J = 1.7, 5.1Hz , 3H), 1.47 (s, 9H), 1 45 (s, 9H), 1.42 (m, 1H), 0.87 (dd, J = 2.4, 6.7Hz, 6H) MS- (MH) - = 467; (M + H) * = 469, (M + Na) * = 491. 60B (±) - (2R, 3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-4-methyl-2-oxo) pentyl-3 acid t-butyl ester (cs-propen-1-yl) -pyrrole-din-5-carboxylic acid. The (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-methyl) t-butyl ester was reacted butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (8.0 mg, 0.02 mmol) with Dess-Martin Periodinane (10 mg, 0.03 mmol) in dichloromethane (0.1 mL) at room temperature for 1 hour. The reaction was set with 1M aqueous sodium thiosulfate solution and stirred for 20 minutes. The reaction was extracted with dichloromethane (3 x 1 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1: 1 to give the title compound as a colorless semi-solid (yield: 4.8 mg, 61%). 60C t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'S) -1-f- Butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-methyl) pentyl-3- (cs-propen-1-yl) -pyrrolidin-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1 -acetic acid or 4-methyl-2-oxo) pen was reacted til-3- (cs-pro pen-1-yl) -pyrrolidine-5-carboxylic acid (4.8 mg, 0.01 mmol) in methanol (0.1 mL) with sodium borohydride (2.0 mg, 0.05 mmol) at room temperature for 0.5 hours . The solvent was removed in vacuo and water (1 mL) was added. The aqueous layer was extracted with dichloromethane (3 x 1 mL). This organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1: 1 to give the title compound t-butyl ester of (±) - (2 R, 3S, 5 R, 1'R, 2'S) - 1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy-4-methyl) pentyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.4 mg, 51%) 60B salt of the acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydrox? -4-methyl)? Entil-3- (c / s) -propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-methyl) pentyl-3-t-butyl ester. - (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester -1-f-butoxycarbonyl-2 - (1-acetamido-2-h id roxi) buti l-3- (cs-propen-1-yl) -pi rrol id i n-5-ca rboxí ico (yield: 4.4 mg, 100%). 1H NMR (D20) d 5.45 (m, 1H), 5.15 (t, J = 11.0Hz, 1H), 3.88 (m, 1H), 3.62 (t, J = 8 OHz, 1H), 3.43 (br t, 1H ), 298 (m, 1H), 2.36 (m, 1H), 1.81 (s, 3H), 1.60 (m, 1H), 1.51 (m, 1H), 1.45 (dd, J = 1.3, 5.4Hz, 3H) , 1.17 (m, 3H), 0.74 (dd, J = 6.7, 14Hz, 6H) MS: (MH) - = 311; (M + H) * = 313, (M + Na) * = 335.

Example 61 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-4-methyl) pentyl-3- (cs-propen- 1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-methyl) pentyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-) acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 1.7 mg, 85%). 1H NMR (DMSO-dβ) d 7.61 (d, J = 9.8Hz, 1H), 5.45 (m, 1H), 5.24 (t, J = 7.4Hz, 1H), 4.29 (br t, 1H), 4.0 (br t, 1H), 3.83 (m, 1H), 3.49 (t, J = 8.8Hz, 1H), 3.13 (m, 1H), 2.39 (m, 1H), 1.82 (s, 3H), 1.68 (m, 2H), 1. 55 (dd, J = 1.4, 5.4Hz, 3H), 1.31 (m, 1H), 1.04 (m, 1H), 0.86 (dd, J = 6.4, 8.3Hz, 6H) MS: (M-H) - = 311; (M + H) * = 313, (M + Na) * = 335.

EXAMPLE 62 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy) pent-3-ynyl) -3- (c / ') s-propen-1-ip-ρrolidin-5-carboxylic acid. 62A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester v t-butyl ester of (±) - (2R.S, 5R.1'R, 2'R) acid -1-f-Butoxycarbonyl-2- (1-Acetamido-2-hydroxy) pent-3-vn? L) -3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, but using propin-1-yl zinc in place of ethyl magnesium bromide to give t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pe nt-3-ynyl-3- (c / s-propen-1-yl) -pi rrol id in-5-ca rboxí lico (yield: 0.0073 g, 16%) and acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido) 2-hydroxy) pent-3-ynyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0349 g, 77%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 451, (M + Na) * = 473, (2M + Na) * = 923,. (M-H) - = 449. (±) - (2R, 3S, 5R, 1'R, 2'R) MS: (M + H) * = 451, (M + Na) * = 473, (2M + Na) * = 923, (MH ) "= 449. 62B salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'S) -2- (1-Acetamido-2-hydrox?) Pent-3-vnil) -3- (c / s -propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2 R, 3S, 5R) t-butyl ester , 1 'R, 2' S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) pent-3-ynyl-3- (cs-propen-1-yl) -pyrrolidin-5 -carboxylic acid instead of t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetam ido-2-h id roxi) bu til-3- (cs-propen-1-yl) -pyrro li i n-5-carboxylic acid (yield: 0.0052 g, 100%). H NMR (DMSO-de) 5 7.97 (d, J = 8.3 Hz, 1H), 5.48 (m, 1H), 5.25 (m, 1H), 4.35-4.20 (m, 3H), 3.67 (m, 1H), 3.18 (quint., 8.8Hz, 1H), 2.41 (dt, J = 12.7.7.8Hz, 1H), 1.84 (s, 3H), 1.81 (d, J = 1.9Hz, 3H), 1.63 (m, 1H) , 1.59 (dd, J = 6.9.2.0Hz, 3H). MS: (M + H) * = 295, (M + Na) * = 317, (M-H) "= 293, (M + CF3COO = 407, (2M-H) '= 587.

Example 63 Sa1 of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R.2'R) -2- (1-Acetamido-2-hydroxy) pent-3-vnil) -3- (c s- propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pent-3-ynyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-) acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0540 g, 100%). ? NMR (DMSO-de) d 7.90 (d, J = 88 Hz, 1H), 5.50 (m, 1H), 5.25 (m, 1H), 4.40-4.35 (m, 2H), 4.28 (m, 1H), 3.71 (t, J = 8.0 Hz, 1H), 3.18 (quint., 8.3Hz, 1H), 2.42 (dt, J = 13.2.7.4Hz, 1H), 1.87 (s, 3H), 1.82 (d, J = 1.9Hz, 3H), 1.71 (dt, J = 12.7, 10.0Hz, 1H), 1.57 (dd, J = 6.9.1.5Hz, 3H). MS: (M + H) * = 295, (M + Na) * = 317, (M-H) "= 293, (M + CF3COO) = 407.

EXAMPLE 64 Salt of tpfluoroacetic acid of (±) - (2R, 3S, 5R, 1'R.2'R) -2- (1-Ace-tamido-2-hydroxy-2-heptaf luoropropyl) ethyl- 3- (c / 's- propen-1 -i D-pi rrol id in -5-carboxylic 64A t-butyl ester of (±) - (2R.3S.5R.1 'R.2'R) -1-f- Toxic Bu rbonyl-2- (1-acetamido-2-hydroxy-2-) heptafl uoro pro pil) ethyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'R) -1- f- Butoxycarbonyl 2- (1-acetamido-1-formyl) methyl-3- (c /) acid t-butyl ester was reacted. s-propen-1-yl) -pyrrolidine-5-carboxylic acid (41 mg, 0.10 mmol) and heptafluoropropyl iodide (0.144 mL, 1.0 mmol, 10 equivalents) in THF (2 mL) with 1M phenylmagnesium bromide (0.90 mL, 0.90 mmol, 9 equivalents) at -78 ° C for 5 minutes. The reaction mixture was allowed to take the room temperature after 1 h. The reaction was set up with saturated aqueous solution of ammonium chloride (10 mL) and water (10 mL) followed by extraction using ethyl acetate (3 X 25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1/2 to give the title compound t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2 'acid R) -1-f-bu toxic rboni I 2- (1 -acetam ido-2-hydroxy-2-heptaf Ioropropyl) eti I-3- (c s-propen-1-yl) -p? rrolid? n-5-carboxyl? co (yield: 12.6 m? 22%) (±) - (2R, 3S, 5R, 1'R, 2'R) MS: (M + H) * = 581, (M + Na) * = 603, (2M + Na) * 1183, (M-H) - = 579. 64B acid trifluoroacetic acid salt (±) - (2R.3S.5R.1'R.2'R) - 2- (1-Acetamido-2-hydroxy-2-heptafluoropropyl) ethyl-3- (c / s) -propen-1-yl) -? -rolyolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-heptafluoropropyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydrox?) butyl-3- (t) butyl ester. c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0003 g, 100%). 1 H NMR (DMSO-d 6) d 7.84 (d, J = 9.3 Hz, 1 H), 5.45 (m, 1 H), 5.26 (m, 1 H), 4.71 (t, J = 9.7 Hz, 1 H), 4.63 (d, J = 22.0 Hz, 1H), 4.51 (m, 1H), 3.59 (t, J = 9.3 Hz, 1H), 3.19 (quint., 8.3Hz, 1H), 2.43 (dt, J = 12.7.7.3Hz, 1H ), 1.76 (s, 3H), 1.74 (m, 1H), 1.53 (dd, J = 6.8.1.4Hz, 3H). MS: (M + H) * = 425, (M + Na) * = 447, (M-H) '= 423, (2M-1)' = 847.

Example 65 Salt of trifluoroacetic acid acid (± H2R, 3S.5R, 1'R, 2'S) -2-MA ceta mi do-2.4-di hydroxy) but? L-3- (cs-pro pen- 1-il ) -p? id-5-carboxylic acid 65A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester -1-f- Butoxycarbonyl-2- (1-acetamido-2,4-dihydroxy) but? L-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxylic acid. Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-ethoxycarbonyl) ethyl ester was reacted 3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (35 mg, 0.07 mmol) with lithium borohydride (8 mg, 0.35 mmol) in THF (5 mL) at 25 ° C for 3 hours. The reaction was set up with saturated aqueous solution of ammonium chloride (2 mL) and water (2 mL) followed by extraction using dichloromethane (2 X 10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 5% methanol in dichloromethane to give the title compound t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1 -f-butoxycarbonyl 2- (1-acetamido-2,4-dihydrox) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield 14 mg, 44%). (±) - (2R, 3S, 5R, 1'R, 2'S) = MS. (M + H) * = 457, (M-H) "= 455 65B salt of trifluoroacetic acid of (+) - (2R.3S.5R.1'R, 2'S) -2- (1-Acetamido-2,4-dihydrox) butyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (+) - (2R, 3S, 5R, 1'R) t-butyl ester , 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2,4-dihydroxy) butyl 3- (c / s-propen-1-yl) -pyrrole-din-5-carboxylic acid instead of t- butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen- 1-yl) -pyrro! Idin-5-carboxylic acid. H NMR (DMSO-de) d 7.93 (d, J = 9.0Hz, 1H), 5.56 (m, 1H), 5.31 (m, 1H), 4.43 (m, 1H), 4.14 (m, 1H), 3.69 (m, 1H), m, 1H), 3.63 (m, 1H), 3.23 (m, 2H), 3.07 (m, 1H), 2.43 (m, 1H), 2.06 (s, 3H), 1.83 (m, 2H), 1.79 (m , 1H), 1.62 (dd, J = 6.71, 1.22 Hz. 3H) MS: (M + H) * = 301, (MH) "= 299.

Example 66 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'R) -2- (1-Acetamido-2,4-dihydroxy) but? L-3- (c s-propen-1-ip-pyrrole? din-5-carboxylic 66 A (2R, 3S, 5R, 1'R, 2'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2,4-dihydroxy) butyl-3- (c s-propen-1-yl ) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 65A using (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbon t-butyl ester L-2- (1-acetamido-2-hydroxy-3-ethoxycarbonyl) ethyl-3- (c; s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (± ) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-ethoxycarbonyl) etl-3- (c s-propen-1) -yl) -pyrrolidine-5-carboxylic acid. (yield: 11 mg, 70%). 1H NMR (CDCU) d 5.58 (m, 1H), 5.38 (m, 1H), 4.16 (m, 1H), 4.05 (m, 1H), 3.97 (m, 1H), 3.78 (m, 2H), 3.20 ( m, 1H), 2.66 (m, 1H) 2.54 (m, 1H), 2.04 (s, 3H), 1.80 (m, 1H), 1.55 (m, 2H), 1.47 (s, 9H), 1.44 (s, 9H) MS: (M + H) * = 457, (MH) "= 455 66B Salt of trifluoroacetic acid of (+) - (2R.3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2,4-dihydroxy) butyl-3- (c- 's-propen- 1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (+) - (2R, 3S, 5R, 1'R) t-butyl ester , 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2,4-dihydroxy) butyl 3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxicarbon l-2- (1-acetal-2-hydroxy gone) butyl-3- (c s -propen-1-? l) -pyrrolidine-5-carboxylic acid (yield: 8 mg, 96%). ? NMR (DMSO-de) d July 91 (d, J = 9.1 Hz, 1H), 5.50 (m, 1H), 5.25 (m, 1H), 4.43 (m, 1H), 4.30 (m, 1H), 4.22 ( m, 1H), 3.94 (m, 1H), 3.86 (, 1H), 3.62 (m, 1H), 3.18 (m, 1H), 2.43 (, 1H), 1.85 (s, 3H), 1.75 (m, 1H) ), 1.65 (m, 2H), 1.58 (dd, J = 6.70, 1 81 Hz, 3H). MS: (M + H) * = 301, (M-H) "= 299.

Example 67 Methyl ester (±) - (2R.3S.5R.1 'R, 2'S) -2- (1- acetamido-2-h droxi-2- (fenilacetilen-1-yl)) ethyl -3- (c / s-propen-1-pyrrolidin-5-carboxylic acid 67A (+) - (2R .3S.5R.1 'R, 2'R) v (±) - (2R, 3S.5R.V R.2'S) -1-f-Butoxycarbonyl- 2- (1-acetamido-2-hydroxy-2- (phenylacetylene-1-yl)) and tyl-3-y cs-propen-1-? l) -pyrid lid in -5-carboxylic.

The title compounds were prepared according to the method described in Example 41B, but using lithium phenylacetylide instead of ethyl magnesium bromide to give (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2- (phenylacetyl-1-yl)) ethyl-3- (c / s- propen-1-? I) - 15 pyrrolidine-5-carboxylic (yield: 0.0010 g, 4%) and t-butyl ester of (±) - (2R, 3S, 5R, 1 'R, 2') R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2- (phenylacetylene-1-yl)) ethyl-3- (c s-propen-1-yl) -pyrrolidin-5 - carboxylic (yield: 0.0050 g, 21%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 513, (M + Na) * = 535, (2M + Na) * = 1047, (MH) "= 511. (±) - (2R, 3S, 5R, 1'R, 2'R) MS: (M + H) * = 513, (M + Na) * = 535, ( 2M + Na) * = 1047, (MH) = 511. 67B salt of trifluoroacetic acid of (+) - (2R.3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy-2- (phenylacetylene-1-yl)) ethyl-3- (c s-pro? en-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 1C, using (±) - (2) - t-butyl ester R, 3S, 5 R, 1'R, 2 'S) -1-f-bu toxi carbon il-2- (1 -acetam id o-2-hid rox¡-2- (phenylacetylene-1-yl)) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1 'R, 2'S) t-butyl ester -1- fb or toxi carbon il-2- (1 -acetamido-2-hydroxy) butyl-3- (cspro-n-1 -i I) -pyrrolidine-5-carboxylic acid.

EXAMPLE 68 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R.2'R) -2- (1-Acetate mido-2-h id roxy-2-p-phenylacetyl 1-) il)) ethyl-3- (c s-pro pen- 1 -i D-pyrrolidin-5-carboxylic acid 68A salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.2'R) -2- (1-Acetamido-2-hydroxy-2- (phenylacetylene-1-yl)) ethyl-3-fc s-propen-1-yl) -? irrolidin-5-carboxyl The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy-2- (phenylacetylene-1-yl)) ethyl-3- (c / s-? ropen-1-yl) -pyrrolidine-5-carboxylic acid instead of t- Butyl ester of acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxi carbon i l-2- (1 -acetam id o-2-hid roxi) buti l-3 - (c / s-pro pen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0034 g, 100%). 1 H NMR (DMSO-de) d 9.2 (bs, 1H), 8.04 (d, J = 9.2 Hz, 1H), 7.45-7.35 (m, 5H), 5.50 (m, 1H), 5.29 (m, 1H), 4.64 (d, J = 4.9, 1H), 4.5-4.4 (m, 2H), 3.81 (m, 1H), 3.22 (quint., J = 8.5Hz, 1H), 2.45 (dt, J = 12.8.7.3Hz , 1H), 1.89 (s, 3H), 1.74 (dt, J = 12.7, 10.0Hz, 1H), 1.58 (dd, J = 7.3.1.8Hz, 3H). MS: (M + H) * = 357, (M + Na) * = 379, (M-H) "= 355.

Example 69 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-hydroxy-3-ethyl) pentyl-3- (c s-propen -1-yl) -pyrrolidine-5-carboxylic acid 69A (±) - (2R.3S.5R.1 'R) -1-f-Butoxycarbonyl-2- (1-Acetamido-2-oxo-3-ethyl) pentyl-3- (c) acid t-butyl ester ? s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method which is described in Example 42A, using (±) - (2R, 3S, 5R, 1'R, 2 ', R) -1-f-butoxycarbonyl-2- (1-acetamido) t-butyl ester -2-hydroxy-3-ethyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1'R, 2 'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c s -propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 8 mg, 81 %). MS: (M + H) * = 481, (M-H) "= 479 69B t-butyl ester of (±) - (2R, 3S.5R, 1'R, 2'S) -1-f-Bu toxic rbon i I-2-Í1 -Aceta mi do-2-hidroxi-3-eti I) penyl-3- (c s-propen-1 -yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 42B, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-butyl ester. 2- (1-acetamido-2-oxo-3-ethyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxylic acid instead of (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl 2- (1 -acetam-do-2-oxo) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 5 mg , 63%). MS: (M + H) * = 483, (M-H) - = 481 (±) - (2R, 3S, 5R, 1 'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydrox?) butyl-3- (c; s-) acid ester propen-1-? l) -pyrrolidine-5-carboxyl? co (yield: 7.5 mg, 100%). H NMR (DMSO-de) d 783 (d, J = 9.2Hz, 1H), 7.36 (m, 2H), 7.32 (m, 2H), 7 25 (m, 1H), 5.47 (, 1H), 5.33 ( m, 1H), 4.54 (d, J = 9.8Hz, 1H), 4.36 (m, 1H), 4.23 (m, 1H), 3.78 (m 1H), 3.20 (m, 1H), 2.43 (m, 1H) , 1.63 (m, 1H), 1.56 (dd, J = 6.7, 1.2Hz, 3H), 1.53 (s, 3H) MS: (M + H) * = 333, (M + Na) * = 355, (MH ) - = 331.

Example 73 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R.2'R) -2- (1-Acetamido-2-hydroxy-2- (tofen-2-yl) ) ethyl-3- (c s-propen-1-? l -pyrrolidine-5-carboxylic acid) Bu toxic rbon i l-2- (1 -acetam ido-2-hydroxy-2- (thiof en-2-yl)) and il-3- (c s-propen-1-yl) -pyrrolidin-5-ca rboxí lico. acid t-butyl ester (±) - (2R, 3S, 5R, 1 'R) -1-f-Butoxycarbonyl 2- (1-acetamido-2-formyl) ethyl-3- (c / s-propen-1) -yl) -pyrrolidine-5-carboxylic acid (40 mg, 0.098 mmol) in THF (2 mL) was added dropwise to a solution of 2-thienyl lithium (1M in THF, 0 505 mmol, 5 equivalents) in THF (1 L) at 25 ° C was reacted for 20 minutes The reaction "* --- • ---- • - • - was set with aqueous ammonium chloridesaturated (2 mL) and water (5 L) followed by extraction using dichloromethane (2 X 10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified through column chromatography on silica gel using 1/1 ethyl acetate / hexane to give the title compound (yield 9 5 mg, 20%) MS (M + H) * = 495, (M + Na) * = 517 , (MH) = 493 73B salt of the acid tpfluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydrox? -2- (t? Ofen- 2-? L)) et? L-3- (c < s-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co The title compound was prepared in accordance with the method described in Example 41C, using t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butox? carbon? l-2- ( 1-acetamido-2-hydrox? -2- (t? Ofen-2-? L)) et? L-3- (c; s-propen-1-? l) -pyrrolidone-5-carboxyl? co instead of acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butox? Carbon? L-2- (1 -acetam id o-2-h? Drox?) Bu ti l-3- (c / sp rapen- 1-? L) -p? id-5-carboxylic acid (yield 4 3 mg, 100%) 1 H NMR (DMSO-de) d 786 (d, J = 98 Hz, 1 H), 763 (dd, J = 54, 1 0 Hz, 1 H) , 707 (m, 1 H), 6 98 (m 1 H), 58 (m, 1 H), 543 (m, 1 H), 455 (m, 1 H), 4 39 (m, 1 H), 372 (m 1 H) , 3 11 (m, 2H), 243 (m, 1H), 2 04 (s, 3H), 1 80 (m, 1H), 1 57 (m, 3H) faith" MS: (M + H) * = 339, (M + Na) + = 361, (M-H) 337.

Example 74 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy-3- (4-methyl-lthiazol-2-yl) ) propi l-3- (cs-pro pen-1-yl) -pyrrolidine-5-carboxylic acid 74A t-butyl ester of acid (±) - (2R.3S.5R.1'R, 2'S) y. l ± (2R.3S.5R.1'R.2'R) -1-f-Butoxycarbo2- (1-Acetamido-2-hydroxy-3- (4-methylthiazol-2-yl)) propyl -3- (cs-propen-1-yl-1-pyrrolidine-5-carboxylic acid. 1. 6 M n-Butyllithium (0.125 mL, 0.20 mmol, 4 equivalents) was added to a solution of 2,4-dimethylthiazole (28.3 mg, 0.25 mmol, 5 equivalents) in 1 mL of THF at -78 ° C was reacted by 30 min. ((±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbo2- (1 -acetamido-2-formyl) ethyl-3- (cs-) acid t-butyl ester propen-1 -i I) -pyrrolidine-5-carboxylic acid (20.5 mg, 0.050 mmol) in THF (1 mL) was added dropwise to the above solution, reacted for 30 minutes at -78 ° C and then for 30 minutes. minutes at room temperature The reaction mixture was set with saturated aqueous ammonium chloride (5 mL) and water (5 mL) followed by extraction using dichloromethane (3 X 25 mL) .The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified through column chromatography on silica gel using 1/2. ethyl acetate / hexane to give t-butyl ester of (±) - (2R, 3S, 5, 1'R, 2'S) -1-f-butoxycarbo2- (1-acetamido-2-hydroxy) -3- (4-Methylthiazol-2-yl)) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 3.3 mg, 13%) and t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbo2- (1-acetamido-2-hydroxy-3- (4-methylthiazol-2-yl)) propyl -3- (c / s-propen-1-? L) -pyrrolidine-5-carboxylic acid (yield: 7.5 mg, 29%). (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 524, (M + Na) * = 546, (2M + Na) * = 1069, (M-H) - = 522. (2R, 3S, 5R, 1'R, 2'R) MS: (M + H) * = 524, (M + Na) * = 546, (2M + Na) * = 1069, (MH) '= 522 . 74B salt of trifluoroacetic acid of f ±) - (2R.3S, 5R, 1'R, 2'S) -2- (1-Acetam id o-2-h id roxi-3- (4-me ti I ti azole -2-i I)) propyl-3-fc s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbo2- (1-acetamido-2-hydrox? -3- (4-methylthiazole- 2-? L)) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxicarbo ni l-2- (1 -ace tamido-2-hydrox) ) Buyl-3- (c / s-pro pen-1-yl) -p-rrolidin-5-carboxylic acid (yield: 0.0030 g, 100%). 1H NMR (DMSO-de) d 9.0 (bs, 1H), 8.10 (d, J = 8.3Hz, 1H), 7.11 (d, J = 1.0 Hz, 1H), 5.48 (m, 1H), 5.30 (m, 1H), 4.30 (m, 1H), 4.10 (, 1H), 3.88 (dt, J = 9.4.2.6Hz, 1H), 3.78 (m, 1H), 3.25-3.15 (m, 2H), 2.93 (dd, J = 15.1, 8.3Hz, 1H), 2.41 (dt, J = 12.3.7.3Hz, 1H), 2.33 (d, J = 1.0Hz, 3H), 1.86 (s, 3H), 1.66 (dt, J = 12.7 , 10.3Hz, 1H), 1.61 (dd, J = 6.8.1.5Hz, 3H). MS: (M + H) * = 368, (M + Na) + = 390, (M-H) - = 366.

Example 75 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R, 2'R) -2- (1-Acetamido-2-hydroxy-3- (4-methylthiazol-2-yl) ) propyl-3- (c / s-propen-1-yl) -pyrrol id i n-5-ca rboxí lico The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- t-butyl ester butoxycarbo2- (1-acetamido-2-hydroxy-3- (4-methylthiazol-2-yl)) propyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f- . & .. butoxycarbo2- (1-acetamido-2-hydroxy) butyl-3- (c ('s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0030 g, 100%). 1 H NMR (DMSO- de) d 9.0 (bs, 1H), 7.77 (d, J = 9.3Hz, 1H), 7.11 (s, 1H), 5.47 (m, 1H), 5.25 (m, 1H), 4.45 (m, 1H), 4.20 (m, 2H), 3.58 (t, J = 9.1Hz, 1H), 3.19 (m, 1H), 2.96 (m, 2H), 2.41 (m, 1H), 2.33 (d, J = 1.0Hz, 3H ), 1.85 (s, 3H), 1.73 (dt, J = 12.7, 10.3Hz, 1H), 1.54 (dd, J = 6.9.1.5Hz, 3H) MS: (M + H) * = 368, (M + Na) + = 390, (MH) - = 366, (M + CF 3 COOH) - = 480, (2M-H) "= 733.

Example 76 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1 'R, 2'RS) -2- (1-Acetamido-2-hydroxy-3- (thiazolin-2-yl)) propyl -3- (c s-propen-1-yl) -pyrrolidin-5-carboxylic acid 76A. acid t-butyl ester (±) - (2R.3S.5R.1'R.2'RS) -1-f- Butoxycarbonyl-2- (1-Acetamido-2-hydroxy-3- (thiazolin-2- il)) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid t-butyl ester (±) - (2R, 3S, 5R, 1'R) -1-f- Butoxycarbonyl 2- (1-acetamido-2-formyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (20.5 mg, 0.05 mmol) in THF (1 mL) was added dropwise to a solution of (thiazolin-2-yl) methyl lithium (0.20 mmol, 4 equivalents, prepared from 0.025 g of 2-methylthiazoline and 0.125 mL of 1.6 M n-BuLi at -78 ° C) in THF (2 mL) a -78 ° C was reacted for 30 minutes. The reaction was perfused with saturated aqueous ammonium chloride (5 mL) and water (5 mL) followed by extraction using dichloromethane (3 X 20 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 1/1: ethyl acetate / hexane to give the title compound as a mixture of isomers (yield: 10 mg, 40%). MS: (M + H) * = 512, (M + Na) * = 534, (M-H) '= 510. 76B salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R, 2'RS) -2- (1- Acetamido-2-hydroxy-3- (ti azol in-2-il) ) pro? il-3- (cs-propen-1 -i I) -pyrrolidine-5-carboxylic acid The title compounds were prepared according to the method described in Example 41C, using t-butyl ester of the acid ( ±) - (2R, 3S, 5R, 1'R, 2'RS) -1-r-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3- (thiazolin-2-yl)) propyl-3 (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl- t-butyl ester 2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) - pyrrolidin-5-carboxyl? co (yield: 0003 g, 100%) Main isomer 1 H NMR (DMSO-d 6) d 8.88 (m, 1 H), 7.76 (d, J = 8.8 Hz, 1 H), 5 46 ( m, 1H), 5.19 (m, 1H), 4 69 (m, 1H), 3.90 (m, 1H), 3.85 (m, 1H), 3.49 (m, 2H), 3.35 (t, J = 9.0Hz, 1H), 3.29 (dd, J = 17.6, 5.9Hz, 1H), 3.04 (t, J = 8.9Hz, 1H), 2.78 (dd, J = 17.6.8.1 Hz, 1H), 2.7-2.55 (m, 2H ), 1.75 (s, 3H), 1.70 (m, 1H), 1.56 (dd, J = 6.8.1.5Hz, 3H). MS: (M + H) * = 356, (M + Na) * = 378, (2M + Na) * = 733, (M-H) = 354.

Example 77 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R.1'R.2'S) -2- (1-Acetamido-2-hydroxy-3,3-difluoro-3-vinyl) propyl-3 - (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid 77A (±) - (2R.3S, 5R.1'R.2'S) -1-t-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3,3-difluoro-) t-butyl ester 3-vinyl) propyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid t-butyl ester (±) - (2R, 3S, 5R, 1'R) -1-f- Butoxycarbonyl 2- (1-acetamido-2-formyl) ethyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (41 mg, 0.10 mmol) and 1,1-difluoroalide iodide (94 mg , 0.60 mmol, 6 equivalents) in THF (2 mL) was reacted with zinc powder (33 mg, 0.50 mmol, 5 equivalents) at 0 ° C for 5 minutes and then at room temperature for 4 hours. The reaction mixture is Fractioned with saturated aqueous ammonium chloride (15 L) and water (15 L) and extracted with 3 X 25 mL dichloromethane. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 1/3: ethyl acetate / hexane to give the title compound (yield: 35 mg, 71%). MS: (M + H) * = 489, (M + Na) * = 511, (2M + Na) * = 999, (M-H) = 487. 77B salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1 'R, 2'S) -2- (1-Acetam-ido-2-hydroxy-3,3-d-flu-3-vi-nyl) propyl I -3- (c / 's-pro pen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3,3-difluoro-3-vinyl) propyl-3- ( cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxic rbo ni -2- (1 -aceta my do-2-hydroxy) b util-3- (cs-propen-1 -i I) -pyrrolidine-5-carboxylic acid (yield: 0.0026 g, 96%). 1H NMR (DMSO-de) d7.68 (d, J = 7.8Hz, 1H), 5.97 (m, 1H), 5.55-5.45 (m, 2H), 5.43 (m, 1H), 5.23 (m, 1H) , 4.45 (m, 2H), 4.10 (m, 1H), 3.16 (quint J = 9.1Hz, 1H), 2.41 (dt, J = 12.8.7.3Hz, 1H), 1.72 (s, 3H), 1.70 ( dt, J = 12.8, 10.3Hz, 1H), 1.61 (dd, J = 6.7.1.2Hz, 3H).

MS- (M + H) * = 333, (M + Na) * = 355, (M-H) "= 331, (2M-H)" = 663 Example 78 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.2'R) -2-f1-Acetamido-2-hydroxy-3,3-d? Fluoro-3-vinyl) prop? l-3- (c / s-propen-1-i0-pyrrolidine-5-carboxylic acid 78A (±) - (2R.3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1-Acetamido-2-oxo-3,3-d-fluoro-) t-butyl ester 3-vini0? Rop? L-3- (c / s-propen-1-yl) -pi rrol id i n-5-caboxylic acid The title compound was prepared according to the method described in Example 42A, using t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3) , 3-difluoro-3-vinyl) propyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy!) Butyl-3- (c; s-propen-1-yl) -pyrrolidine-5-carboxylic acid to give t-butyl ester of (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-oxo-3,3-difluoro-3,3-difluoro-3-vinyl) propyl-3- (c / s-propen-1 -yl) -pyrrolidine-5-carboxylic acid (yield: 0.0050 g, 44%) MS: (M + H) * = 487, (M + Na) * = 509, (M-2F) * = 448, (MH ) _ = 485. 78B t-butyl ester of (+) - (2R.3S.5R, 1'R, 2'RM-f-Butoxycarbonyl-2- (1-Acetamido-2-hydroxy-3,3-difluoro-3-vinyl) ) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 42B, using t-butyl ester of the acid ( ±) - (2 R, 3S, 5 R, 1'R) -1-t-butoxy carbon il-2- (1 -acetam id 0-2-0X0-3-difluoro-3-vinyl) propyl-3- (c ?s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1'R) -2- (1-acetamido-2-oxo) butyl-3- (c s) -propen-1-yl) -pyrrole-din-5-carboxylic acid. 78C salt of the acid trifluoroacetic acid (±) -f2R.3S.5R.1'R.2'R) -2- (1-Acetamido-2-hydroxy-3,3-difluoro-3-vinyl) propyl-3 - (c? 's-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 41C, using t-butyl ester of (±) - ( 2R, 3S, 5R, 1'R, 2'R) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3, 3-difluoro-3-vinyl) propyl-3- (c s- propen-1-yl) -pyrrolidin-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2-t-butyl ester - (1-acetamido-2-hydrox?) Butyl-3- (cís-propen-1-yl) - - -."My-.,. pyrrolidin-5-carboxylic acid.

Example 79 Salt of trifluoroacetic acid of (±) -> 2R.3S.5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-2-fc / s-buten-2-) il)) ethyl-3- (c? s-propen-1-i0-pyrrolidine-5-carboxylic acid) 79A t-butyl ester of the acid (±) - (2R.3S.5R.1'R.2'R) -1-f-Bu toxi carbon i l-2- (1-Acetam-ido-2-hydroxy-2) -fc s-bu ten-2-yl)) and I-3- (c / s-? ropen-1-yl) -pyrrolidine-5-carboxylic acid. acid t-butyl ester (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1-acetamido-2-formyl) ethyl-3- (c s-propen-1- il) -pyrrolidine-5-carboxylic acid (30 mg, 0.073 mmol) in THF (5 mL) was reacted with c / s-2-buten-2-yl lithium (0.75 mL (0.5M), 0.37 mmol) at 25 ° C for 45 min. The reaction was perfused with aqueous saturated ammonium chloride (5 mL) and water (5 mL) followed by extraction using dichloromethane (2 X 10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified through column chromatography on silica gel using 1/1: ethyl acetate / hexane to give the title compound (yield: 20 mg, 59%). 1H NMR (CDCU) d 6.19 (d, J = 8.9 Hz, 1H), 5.61 (m, 1H), 5.35 (m, 1H), 5.27 (m, 1H), 4.48 (m, 1H), 4.18 (m, 1H), 4.77 (m, 2H), 3.10 (m, 1H), 2. 72 (m, 1H), 1.99 (s, 3H), 1.82 (m, 1H), 1.73 (m, 3H), 1.55 (m, 6H), 1. 47 (s, 9H), 1.44 (s, 9H) MS: (M + H) * = 467, (M-H) "= 465 79B salt of trifluoroacetic acid of (+) - (2R.3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-2- (c? S-buten-2-yl) acid )) ethyl-3- (c / s-propen-1-iD-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (± ) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2- (cs-buten-2-yl)) ethyl-3 - (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxic rbon i-2- (1 -acetamide -2-hydroxy) butyl-3- (cs-propen-1 -i I) -pyrrolidine-5-carboxylic acid (yield: 4 mg, 96%). 1H NMR ( DMSO-dβ) d 8.09 (d, J = 9.0 Hz, 1H), 5.50 (m, 1H), 5.32 (m, 1H), 5.16 (m, 1H), 4.50 (m, 1H), 4.38 (m, 1H) ), 4.19 (m, 1H), 3.43 (m, 1H), 3.20 (m, 1H), 2.43 (m, 1H), 1.88 (s, 3H), 1.74 (m, 1H), 1.70 (s, 3H) , 1.62 (m, 3H), 1.58 (m, 3H) MS: (M + H) * = 311, (MH) - = 309 EXAMPLE 80 Salt of the acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R, 3'R) and (±) - (2R, 3S.5R, 1'R, 2'R, 3'S) -2- (1-Acetam? Do-2-hydroxy-3-methyl) pent? L-3- (c s-propen -1-? L) -pyrrolidine-5-carboxylic acid 80A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'R.3'R) and (±) - (2R.3S. 5R, 1'R.2'R.3'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1 -yl) -pyrrolidine-5-carboxylic acid. t-butyl ester of (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1 -acetamido-1-formyl) methyl-3- (c s-propen-1) -yl) -pyrrolidone-5-carboxylic acid (60 mg, 0.15 mmol) in THF (1 mL) was added dropwise to a solution of 2-butylmagnesium bromide (3M in ether) (0.45 mL, 0.85 mmol) at room temperature was reacted for 40 minutes. The reaction was set with saturated NH 4 Cl (1 L) followed by extraction using dichloromethane (3 x 1 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via column chromatography on silica gel using 1/4: ethyl acetate / hexane to give the title compounds t-butyl ester of (±) - (2R, 3S, 5R, 1'R) , 2'R, 3'S) -1-f-butoxycarbonyl 2- (1-acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid Rf = 0.65 (11 ethyl acetate: hexanes) (yield: 19 mg, 27%) and t-butyl ester of the acid (±) - Mt-y, (2R, 3S, 5R, 1'R, 2'R, 3'R) -1-f-bu toxic rbonyl 2- (1 -acetam id o-2-h id roxi-3-methyl) pentyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid Rf = 0.5) (1: 1 ethyl acetate: hexanes) (yield: 19 mg, 27%). Rf = 0.65 1H NMR (CDCU) d 5.98 (d, J = 8.8Hz, 1H), 5.62 (t, J = 10.5Hz, 1H), 5.35 (m, 1H), 4.66 (d, J = 4.4Hz, 1H ), 4.16 (d, J = 9.5Hz, 1H), 3.78 (m, 3H), 3.12 (m, 2H), 2.73 (m, 1H), 2.0 (s, 3H), 1.81 (d, J = 13.2Hz) , 1H), 1.54 (br s, 3H), 1.47 (s, 9H), 1.44 (s, 9H), 1.25 (m, 1H), 0.81 (m, 6H) MS: (MH) - = 467; (M + H) * = 469. R, = 0.5 1H NMR (CDCU) d 6.00 (d, J = 10.2Hz, 1H), 5.61 (br t, 1H), . 36 (m, 1H), 4.58 (d, J = 4.7Hz, 1H), 4.14 (d, J = 8.8Hz, 1H), 3.82 (m, 3H), 3.13 (m, 2H), 2.73 (m, 1H) ), 1.99 (s, 3H), 1.80 (d, J = 13.9Hz, 1H), 1.54 (br s, 3H), 1.46 (s, 9H), 1.44 (s, 9H), 1.43 (m, 1H), 0.97 (d, J = 6.8Hz, 3H), 0.81 (t, J = 7.2Hz, 3H) MS: (MH) - = 467; (M + H) * = 469. 80B acid trifluoroacetic acid salt (±) - (2R.3S.5R.1'R.2'R, 3'S) -2- (1-Acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R, 2'R, 3'S) -1-f-Bu toxi-t-butyl ester carbon i l-2- (1 -acetam id o-2-hydroxy-3-methyl) pen tyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (2.5 mg, 0.005 mmol) he was made to react with tpfluoroacetic acid (08 mL) in dichloromethane (02 mL) at room temperature for 6 hrs. The reaction was concentrated in vacuo overnight and titrated with acetonitrile (2 x 1 mL) to give the title compound (yield: 2.0 mg, 100%). 1 H NMR (DMSO-d 6) 5 7.68 (d, J = 8.8 Hz, 1 H), 5 45 (m, 1 H), 5.23 (t, J = 7.3 Hz, 1 H), 4.24 (br t, 1 H), 4.18 ( m, 1H), 3.52 (t, J = 7.3Hz, 1H), 3.45 (m, 1H), 3.16 (m, 1H), 2.38 (m, 1H), 1.83 (s, 3H), 1.68 (m, 1H) ), 1.58 (dd, J = 2.0, 4.8Hz, 3H), 1.37 (m, 2H), 0.99 (m, 1H), 0.89 (d, J = 6.8Hz, 3H), 0.79 (t, J = 7.4Hz , 3H) MS: (MH) - = 311; (M + H) + = 313, (M + Na) + = 335.

Example 81 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R.2'R.3'R) -2- (1-Acetamido-2-hydroxy-3-methyl) pentyl-3 -fc s-propen-1-? l) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'R, 3'R) t-butyl ester - 1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-ethyl) pentyl-3- (c / 's- propen-1-yl) -pi rrol idi n-5-ca RBox (R (= 0.5, 1: 1, ethyl acetate: hexanes) in place of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester-1-t- butoxycarbonyl-2- (1-acetamido-2-hydroxy) S ^ z-Z but? l-3- (c / s-propen-1-? l) -pyrrolidine-5-carboxylic acid (yield: 1.6 mg, 76%) 'H NMR (DMSO-de) d 7.55 (d, J = 93Hz, 1H), 5.45 (m, 1H), 5.23 (m, 1H), 4.31 (br t, 1H), 4.20 (t, J = 8.3Hz, 1H), 3.51 (t, J = 9.3Hz, 1H) , 343 (d, J = 7.4Hz, 1H), 3.17 (m, 1H), 240 (m, 1H), 1.80 (s, 3H), 1.70 (m, 1H), 1.55 (dd, J = 1.4, 5.4 Hz, 3H), 1.36 (m, 2H), 1.14 (m, 1H), 0.84 (t, J = 7.3Hz, 3H), 0.73 (d, J = 6.9Hz, 3H) MS: (MH) - = 311; (M + H) * = 313, (M + Na) * = 335.

Example 82 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R, 2'S.3'S) -2- (1-Acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. 82A t-butyl ester of the acid (±) - (2R.3S.5R.1'R.3'RS) -1-f- Bu toxicarbon i l-2- (1 -acetam ido-2-oxo-3- methyl) penyl-3- (c / s-propen-1 -yl) -? -rolidolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 42A, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2, R, 3'RS) -1-f-butoxycarbonyl-2- (1-acetamido-2-h? Roxi-3-et? L)? entil-3- (c / 's-propen-1-? l) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2) t-butyl ester 'R) 1-f- butox? carbonyl-2- (1-acetamido-2-hydroxy) but? l-3- (c / s-propen-1-? l) -pyrrol? d? n-5-carboxyl? acid f? Butyl (yield - 12 mg, 63%). 82B t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'S.3'S) and (±) - (2R, 3S, 5R.1, R, 2'S, 3'R) -1 -f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) pentyl-3-fc-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 42B, using (±) - (2R, 3S, 5R, 1'R, 3'RS) -1-f- t-butyl ester butox? carbon? l-2- (1-acetamido-2-OXO-3-methyl) phenyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic (Rf) = 0.5 and 0.65, 1: 1, ethyl acetate: hexanes) instead of (2R, 3S, 5R, 1'R) -2- (1-acetamido-2-oxo) butyl-3- (c; s- propen-1-yl) -pyrrolidine-5-carboxylic acid to give t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'S, 3'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydrox? -3-met? l) pentyl-3- (c; 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (Rf = 0.15, 1: 1, ethyl acetate: hexanes ) (yield: 6.0 mg, 50%) and t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S, 3'R) -1-f-butoxycarbonyl-2- (1-) acetamid o-2-hydroxy-3-m ethyl) pentyl-3- (cis-pro pen-1-yl) -pyrrole idin-5-carboxylic acid (R (= 0.10, 1: 1, ethyl acetate: hexanes) ( yield: 2.5 mg, 63%). 82C salt of trifluoroacetic acid of the acid _L ± i? (2R, 3S.5R.1'R, 2'S, 3'S) -2- (1-Acetamido-2-hydroxyl-3-methyl) pentyl-3- (c s -propen-1-yl) -pyrrolidine -5-carboxylic acid The title compound was prepared according to the method described ßn ßl Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S, 3'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s- propen-1-yl) -pyrrolidin-5-carboxylic acid (Rf = 0. 15, 1: 1, ethyl acetate: hexanes) in place of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester-1-t-butoxycarbonyl-2- (1-) acetamido-2-hydroxy) butyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 60 mg, 100%). 1H NMR (DMSO-de) d 7.78 (d, J = 9.2Hz, 1H), 5.42 (m, 1H), 5.29 (t, J = 10.3Hz, 1H), 4.08 (m, 1H), 3.96 (br t, 1H), 3.51 (m, 2H), 3.08 (m, 1H), 2.33 (m, 1H), 1.78 (s, 3H) , 1.56 (d, J = 6.3Hz, 3H), 1.52 (m, 1H), 1. 40 (m, 1H), 1.29 (m, 1H), 1.21 (m, 1H), 0.84 (t, J = 7.3Hz, 3H), 0.73 (d, J = 6.9Hz, 3H) MS: (M-H) - = 311; (M + H) * = 313, (M + Na) * = 335.

Example 83 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R, 2'S, 3'R) -2- (1-Acetamido-2-hydroxy-3-methyl) pentyl -3- (c / s-propen-1-M) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, but using (±) - (2R, 3S, 5R, 1'R, 2'S, 3'R) -1 t-butyl ester -f-Butoxycarbonyl-2- (1-acetamidoO-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (R? = 0.10, 1: 1 ethyl acetate: hexanes) in place of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester-1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c s -propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.5 mg, 100%). H NMR (DMSO-de) d 7.85 (d, J = 8.7Hz, 1H), 5. 5 (m, 1H), 5.29 (t, J = 9.3Hz, 1H), 4.20 (m, 2H), 3.63 ( t, J = 8.3Hz, 1H), 3.42 (br d, 1H), 3.14 (m, 1H), 2.41 (m, 1H), 1.79 (s, 3H), 1.62 (m, 1H), 1.58 (d, J = 5.4Hz, 3H), 1.43 (m, 2H), 1.0 (m, 1H), 0.88 (d, J = 6.8Hz, 3H), 0.80 (t, J = 7.3Hz, 3H) MS: (MH) - = 311; (M + H) * = 313, (M + Na) * = 335.

EXAMPLE 84 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetam-o-2-methoxy) butyl-3- (c? S-propen- 1-yl) -pyrrole-din-5-carboxylic acid 84A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'S) -1-f- Bu toxic rbon i l-2- (1-acetamido-2-methoxy) bu ti I- 3- (c / 's- pro pen- 1 -i D-Pyrrolidin-5-carboxylic acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-Butoxycarbonyl -2- (1-acetamido-2-hydroxy?) Butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (22 mg, 0.05 mmol) was reacted with methyl iodide (0.016) mL, 0.25 mmol), potassium hydroxide (14 mg, 0.25 mmol) and 18-crown-6 (0.7 mg, 0.0025 mmol) in N, N-dimethylformamide (2 mL) at room temperature for 23 hours, then water was added. (5 mL) was added to the reaction mixture, followed by extraction with ether (2 x 10 mL) The organic layer was washed with water and brine, dried over MgSO 4, filtered and concentrated in vacuo. by chromatography on silica gel using 66% ethyl acetate / hexanes to give the title compound, as a colorless oil (yield: 5.2 mg, 23%) MS: (M + H) * = 455, (MH) - = 453. * "* • * - •" "" " 84B salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1'R.2'S -2- (1-Actamido-2-methoxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S t-butyl ester) ) -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) ) -pyrrolidone-5-carboxylic acid (yield: 4.7 mg, 98%) .1H NMR (DMSO-d6) 5 7.96 (d, J = 9.2Hz, 1H), 5.50 (m, 1H), 5.24 (m, 1H), 4.25 (m, 2H), 3.70 (m, 1H), 3.23 (s, 3H), 3.19 (m, 2H), 2.40 (m, 2H), 1.86 (s, 3H), 1.68 (m, 2H), 1.62 (dd, J = 7.0, 1.8Hz, 3H), 1.39 (m, 1H), 0.77 (t, J = 7.3Hz, 3H) MS: (M + H) * = 299, ( M + Na) + = 321, (MH) - = 297 Example 85 Salt of the tpfluoroacetic acid of (±) - (2R, 3S, 5R, VR, 2'R) -2- (1-Acetamido-2-methoxy) butyl-3- (cis-propen-1-yl) -pyrrole din-5-carboxylic 85A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1-acetamido-2-methoxy) butl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- 10 B utoxy carbo nyl-2- (1 -acetamido-2-hydroxy) buyl-3- (cis-pro pen-1 -i I) -pyrrolidine-5-carboxylic acid (17 mg, 0.04 mmol) was reacted with methyl iodide (28 mg, 0.19 mmol), potassium hydroxide (8 mg, 0.19 mmol) and 18-crown-6 (0.002 mmol) in N, N-dimethylformamide (1.5 mL) at room temperature for 6 hours. Then it was added Water (5 mL) was added to the reaction mixture, followed by extraction with ether (2 x 10 mL). The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexanes to give the title compound, (yield: 5 mg, 29%). MS: (M + H) * = 455, (M-H) - = 453 85B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R, 2'R) -2- (1-Acetamdode-2-methoxy) butyl-3-ic s-propen-1 -yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, t-butyl ester, 2'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t -butyl ester of acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c s- propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 4 mg, 95%). 1 H NMR (DMSO-d 6) 5 8.00 (d, J = 9.8HZ, 1H), 5.57 (m, 1H), 5.35 (m, 1H), 4.42 (m, 1H), 4.28 (m, 1H), 3.95 (m, 1H), 3.54 (m, 1H), 3.28 (s, 3H), 2.80 (m, 1H), 2.30 (m, 1H), 1.92 (s, 3H), 1.65 (m, 1H), 1.60 ( m, 3H), 1.43 (m, 2H), 0.82 (t, J = 7.31HZ, 3H). MS: (M + H) + = 299, (M-H) - = 297 Example 86 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R.2'S) -2- (1-Acetamido-2-methoxy-3-methyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 86A t-butyl ester of the acid (±) - (2R.3S.5R, 1'R.2'S) -1-r- B u toxic rbon il-2- (1 -acetam id Q-2- methoxy-3 -methyl) buyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 84A, using t-butyl ester of (±) - (2 R, 3S, 5 R, 1'R, 2 'S) -1-f-bu toxic rboni l-2- (1 -acetamido-2-h) idroxy-3-methyl) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-t-butoxycarbonyl-2- (1-acetam id or-2-hydroxy) butyl-3- (cs-propen-1-yl) -pi-idol-5-carboxylic acid. 86B salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'S -2- (1-Acetate mi do-2-methoxy-3 me ti I) bu ti I -3- ( c / s- pro pe n-1-yl) -pi rrolid i n- 5-carboxylic The title compound is prepared according to the method ? i ^ aíÉ ^^ t ^ which is described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-) t-butyl ester methoxy-3-methyl) butyl-3- (cs-propen-1-? l) -pyrrole-din-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1 ') t-butyl ester R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrole-dino-5-carboxylic acid.

Example 87 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R, 2'R) -2- (1-Acetamido-2-methoxy-3-methyl) butyl-3- (cs- propen-1-yl) -pyrrolidine-5-carboxylic acid 86A (±) - (2R.3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1 -acetam-do-2-methoxy-3-methyl) acid t-butyl ester butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 84A, using acid t-butyl ester (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) butyl-3- (cs-propen -1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido) t-butyl ester -2-hydroxy) butyl-3- (cs-propen-1-? L) -pyrrolidine-5-carboxylic acid (yield: 6.8 mg, 33%) MS: (M + H) * = 469, (M + Na) * = 491, (M-H) - = 467. 87B salt of the acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'R) -2- (1-Acetamido-2-methoxy-3-m ethyl) buti l-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R) t-butyl ester , 3S, 5R, 1"R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-3-methyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetam id o-2-) t-butyl ester hydroxy) butyl l-3- (cs-propen-1-yl) -pyrrolidine-5-carboxyl ico ester (yield: 6.6 mg, 100%). 1 H NMR (DMSO-de) d 7.65 (d, J = 9.2 Hz, 1H), 5.43 (m, 1H), 5.23 (m, 1H), 4.42 (m, 1H), 4.37 (m, 1H), 3.56 (m, 1H), 3.46 (s, 3H), 3.17 (m , 2H), 2.44 (m, 1H), 1.80 s, 3H), 1.78 (m, 1H), 1.70 (, 1H), 1.57 (dd, J = 6.7, 1.2Hz, 3H), 0.94 (d, J = 6.7Hz, 3H), 0.82 (d, J = 6.7Hz, 3H) MS: (M + H) * = 313, (M + Na) + = 335, (MH) - = 311.

Example 88 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1 'R.2'S) -2- (1-Acetamido-2-methoxy) pentyl-3- (c; s-propen-1-) il) -pyrrolidine-5-carboxylic acid 88A (±) - (2R.3S.5R.1'R.2'S) -1-f- Butoxycarbonyl-2- (1-acetamido-2-methoxy) pentyl-3- (c / s) acid t-butyl ester -propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 84A, using (±) - (2R, 3S, t-butyl ester, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) -thiyl-3- (c / s-propen-1-yl) -pyrrolidin-5 -carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 11.9 mg, 36%). MS: (M + H) * = 469, (M + Na) + = 491, (M-H) - = 467. 88B salt of trifluoroacetic acid of (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-methoxy) pentyl-3- (c / s-propen-1- il) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S t-butyl ester) ) -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester ( ±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-h id roxi) butyl-3- (c / s-propen- 1 -yl) - pyrrole and di-5-carboxylic acid. (yield: 11.5 mg, 100%). 1 H NMR (DMSO-de) d 7.95 (d, J = 9.8 Hz, 1 H), 5.49 (m, 1 H), 5.23 (m, 1 H), 4.25 (m, 2 H), 3.68 (m, 1 H), 3.24 (m, 1 H), s, 3H), 3.22 (m, 1H), 3.18 (m, 1H), 2.40 (m, 1H), 1.85 (s, 3H), 1.66 (m, 1H), 1.62 (m, 3H), 1.58 (m , 1H), 1.38 (m, 1H), 1.27 (m, 2H), 0.86 (t, J = 7.3Hz, 3H). MS: (M + H) * = 313, (M + Na) + = 335, (M-H) - = 311. _ Ígi ^^^ EXAMPLE 89 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1 'R.2'R) -2-p-Acetamido-2-methoxy) pentyl-3- (cs-propen-1) -yl) -pyrrolidine-5-carboxylic acid 89A (±) - (2R, 3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1 -acetamido-2-methoxy) pentyl- t-butyl ester 3- (cs- pro pen- 1 -i 0-pyrrolidin-5-carboxylic acid) The title compound was prepared according to the method described in Example 84A, using (±) - (2R) t-butyl ester , 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) pentyl-3- (c / 's-propen-1-yl) -pyrrolidin- 5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl ester -3- (c / s-propen-1-yl) -pyrroli di n-5-carboxylic acid (yield: 4.3 mg, 21%) MS: (M + H) * = 469, (M + Na) * = 491, (MH) - = 467. 89B salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-methoxy) pentyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'R) t-butyl ester. ) -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxy) pentyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-ace tamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -Ir-5-carboxylic acid (yield: 4.8 mg, 100%). 1H NMR (DMSO-de) d 7.70 (d, J = 9.8Hz, 1H), 5.45 (m, 1H), 5.24 ( m, 1H), 4.40 (m, 1H), 4.25 (m, 1H), 3.57 (t, J = 8.5Hz, 1H), 3.40 (m, 1H), 3.35 (s, 3H), 3.17 (m, 1H) ), 2.42 (m, 1H), 1.82 (s, 3H), 1.69 (m, 1H), 1.56 (dd, J = 7.1, 1.2Hz, 3H), 1.24 (m, 4H), 0.88 (t, J = 7.0Hz, 3H) MS: (M + H) * = 313, (M + Na) + = 335, (MH) - = 311 EXAMPLE 90 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1'R, 2'S) -2- (1-Acetamido-2-methoxy-2-allyl) ethyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid 90A (±) - (2R, 3S.5R.1'R.2'S) -1-f- Butoxycarbonyl-2- (1-acetamido-2-methoxy-2-allyl) ethyl-3- (c s-propen-1-yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 84A, using (±) - (2R, 3S) t-butyl ester , 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-allyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidin-5 -carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3 acid t-butyl ester - (c s-propen-1-yl) -pi rrol id i n- 5-carboxylic (yield: 8 mg, 31%). MS: (M + H) * = 467, (M-H) = 465 90B salt of the acid trifluoroacetic acid (±) - (2R, 3S.5R, 1'R, 2'S) -2- (1-Acetamido-2-methoxy-2-allyl) ethyl-3- (c? 'S- propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-2-allyl) ethyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxyl? Co in place of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-) t-butyl ester acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 6 mg, 96%). 1 H NMR (DMSO-dβ) d 8.02 (d, J = 8.6HZ, 1H), 5.75 (m, 1H), 5.51 (m, 1H), 5.24 (m, 1H), 5.05 (m, 2H), 4.27 ( m, 1H), 4.22 (m, 1H), 3.74 (m, 2H), 3.26 (s, 3H), 3.18 (m, 1H), 2.47 (m, 1H), 2.39 (m, 1H), 2.17 (m , 1H), 1.87 (s, 3H), 1.67 (m, 1H), 1.63 (dd, J = 6.71, 1.23 HZ, 3H). MS: (M + H) * = 311, (M-H) - = 309 Example 91 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R.2'R) -2- (1-Acetamido-2-methoxy-2-allyl) ethyl-3- (cs- propen-1-yl) -pyrrolidine-5-carboxylic acid 91A (±) - (2R, 3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1 -acetamido-2-methoxy-2-allyl) ethyl t-butyl ester -3- (cs-propen-1 -i I) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 84A, using acid t-butyl ester ( ±) - (2 R, 3S, 5 R, 1'R, 2'R) -1-f-bu toxi carboni l-2- (1 -acetamido-2-hydroxy-2-) allyl) ethyl-3- (cs-pro? en-1-yl) -pyrrolidin-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 4.0 mg , 16%). MS: (M + H) * = 467, (M-H) - = 465 91B salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R.1'R, 2'R) -2- (1-Acetamido-2-methoxy-2-allyl) ethyl-3- (c; ' s-? ropen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, t-butyl ester, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-2-allyl) ethyl-3- (cs-propen-1-yl) - pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl acid t-butyl ester -3- (c; s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 3 mg, 96%). 1 H NMR (DMSO-de) d 7.75 (d, J = 9.2 HZ, 1H), 5.75 (m, 1H), 5.47 (m, 1H), 5.24 (m, 1 H), 5.06 (m, 2H), 442 (m, 1H), 4.25 (m, 1H), 3.58 (m, 1H), 3.50 (m, 1H), 3.37 (s, 3H), 3.17 (m, 1H), 2.42 (m, 1H), 2.36 ( m, 1H), 1.83 (s, 3H), 1.71 (m, 1H), 1.55 (dd, J = 673, 1.83 HZ, 3H) MS: (M + H) * = 311, (MH) '= 309 EXAMPLE 92 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Actatamido-2-hydroxy-4-vinyl) butyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid. 92A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester and (±) - (2R.3S.5R.1'R, 2'R) -1-f-Butoxycarbonyl -2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 1B, but using 1-buten-4-yl magnesium bromide instead of ethyl magnesium bromide to give the t-butyl ester of the acid (±) - ( 2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (c / s-pro en-1-yl) -pyrrolidine-5-carboxylic acid (yield, 0.0030 g, 6%) and t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0. 0145 g, 28%). (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 467, (M + Na) * = 489, (2M + Na) * = 955, (MH) - = 465. (±) - (2R, 3S, 5R, 1'R, 2, R) MS: (M + H) * = 467, (M + Na) * = 489, (2M + Na) * = 955, (MH ) - = 465. 92B salt of the acid tpfluoroacetic acid of (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy-4-vinyl) butyl-3- (c / s-propen - 1-yl) - pyrrole idin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1) t-butyl ester 'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / ') t-butyl ester s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0027 g, 100%). 1H NMR (DMSO-d6) d 8.93 (bs, 1H), 7.90 (d, J = 9.2 Hz, 1H), 5.80 (m, 1H), 5.48 (m, 1H), 5.28 (m, 1H), 5.00 (m, dd, J = 17.1, 1.8Hz, 1H), 4.94 (dd, J = 10.4.1.8Hz, 1H), 4.29 (bt, J = 8.3Hz, 1H), 4.03 (m, 1H), 3.71 (m, 1H ), 3.49 (m, 1H), 3.15 (quint., J = 8.5Hz, 1H), 2.41 (dt, J = 12.8.7.3Hz, 1H), 2.16 (M, 1H), 2.05 (m, 1H), 1.83 (s, 3H), 1.79-1.75 (m, 1H), 1.64 (m, 1H), 1.58 (dd, J = 6.7.1.8Hz, 3H), 1.34 (m, 2H). MS: (M + H) * = 311, (M + Na) * = 333, (M-H) - = 309, (M + CF3COO -) - = 423 Example 93 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1 'R, 2'R) -2- (1-Acetamido-2-hydroxy-4-vinyl) butyl-3- (c) s-propen-1-yl) -pyrrolidine-5-carboxylic acid. 93A salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxy-4-vinyl) butyl-3- (c / ' s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R) t-butyl ester , 1, R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (t) butyl ester. c / s-propen-1-yl) -pyrrolidin-5-carboxy Meo (yield: 0.0027 g, 100%). 1 H NMR (DMSO-dβ) d 7.68 (d, J = 9.6 Hz, 1H), 5.81 (m, 1H), 5.48 (m, 1H), 5.25 (m, 1H), 5.01 (dd, J = 17.1, 1.8 Hz, 1H), 4.95 (dd, J = 10.3.1.7Hz, 1H), 4.43 (t, J = 8.5Hz, 1H), 4.10 (m, 1H), 3.74 (m, 1H), 3.56 (t, J = 8.9Hz, 1H), 3.16 (quint., J = 8.9Hz, 1H), 2.42 (dt, J = 12.8.7.3Hz, 1H), 2.11 (M, 1H), 2.07 (m, 1H), 1.83 ( S, 3H), 1.72 (dt, J = 12.8, 9.8Hz, 1H), 1.55 (dd, J = 6.7.1.8Hz, 3H), 1.5-1.35 (m, 2H). MS: (M + H) * = 311, (M + Na) * = 333, (M-H) - = 309, (M + CF3COO) = 423, (2M-H) '= 619.

Example 94 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1 'R, 2'S.3'S) -2- (1-Acetamido-2-methoxy-3-methyl) pentyl-3- (cs- propen-1-yl) -pyrrolidine-5-carboxylic acid 94A (±) - (2R.3S, 5R, 1'R.2'S.3'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxy-3-methyl) pentyl- t-butyl ester 3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 84A, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2"S, 3'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-buxylcarbonyl-2-t-butyl ester (1-acetamido-2-hydroxy) bu ti l-3- (c / s-propen-1-yl) -pyrrolidone-5-carboxylic acid. 94B salt of acid trifluoroacetic acid ±. (2R, 3S, 5R, 1'R, 2'S, 3'S) -2- (1-Acetamido-2-methoxy-3-methyl) pentyl-3- (c / s-propen-1-yl) -Pyrrolidin-5 carboxylic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S, 3'S) t-butyl ester. f-butoxycarbonyl-2- (1-acetamido-2-methoxy-3-methyl) pentyl-3- (c / s-propene-1-yl) -pyrrolidine-5-carboxylic acid instead of t -butyl ester of acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) buyl-3- (c / ' s-prop en-1-yl) -pyrrolidine-5-carboxylic acid.

Example 95 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'RS) -2- (1-Acetamido-2-oxo-2-heptafluoropropyl) ethyl-3- (cs-propen-1- il) -pyrrolidine-5-carboxylic acid 95A (±) - (2R, 3S, 5R, 1'RS) -1-f-Butoxycarbonyl-2- (1-Acetamido-2-oxo-3-heptafluoropropyl) ethyl-3- (c) acid t-butyl ester / s-propen-1-yl) -pyrrolidine-5-carboxylic acid.

^^^^^^^^ The title compound was prepared according to the method described in Example 42A, using (±) - (2R, 3S, 5R, 1'R, 2'RS) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy? -3-heptafluoropropyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid by t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) bu ti l-3- (c / s-propen-1- il) -pi-idrol-5-carboxylic acid (yield: 6.8 mg, 88%). MS: (M + H) * = 579, (M-H) = 577. 95B salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'RS) -2- (1-Acetamido-2-oxo-2-heptafluoropropyl) ethyl-3- (c / s-propen-1) -iD-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'RS) t-butyl ester - 1-t-Butoxycarbonyl-2- (1-acetamido-2-oxo-3-heptafluoropropyl) ethyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester ( ±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) buyl-3- (cs-propen-1 -i I) -pyrrolidine-5-carboxylic acid (yield: 0.0037 g, 100%) MS: (M + H) * = 423, (MH) = 421.

Example 96 Salt of tpfluoroacetic acid of (±) - (2R.3S, 5R, 1'RS) -2- (1- Acetamido-2-oxo-2-heptafluoropropyl) et? L-3- (cs- propen-1-? l) -pyrrolidine-5-carboxylic acid 96A (±) - (2R, 3S.5R.1'RS) -1-f-Butoxycarbonyl-2- (1-Acetam-ido-2-oxo-3-heptafluoropropyl) ethyl-3- (butyl) ester c / s-propen-1-yl) -pyrrolidone-5-carboxylic acid. The title compound was prepared according to the method described in Example 42A, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl- (5) -butyl ester. 2- (1-acetamido-2-hydroxy-3-heptafluoropropyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid by t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamide-2-h id roxl) butyl-3- (cs-propen-1-yl) -pyrrolidin-5 -carboxylic (yield: 6.8 mg, 88%). MS: (M + H) * = 579, (M-H) - = 577. 96B (+) - (2R, 3S.5R.1'RS) -2- (1-Acetamido-2-oxo-2-heptafluoropropyl) ethyl-3- (c / s-propen-1) acid trifluoroacetic acid salt -yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, t-butyl ester, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-heptaf luoropropyl) ethyl-3- (c ('s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -aceta mi do-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0037 g, 100%) MS: (M + H) * = 423, (MH) - = 421.

Example 97 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R) -2- (1-Acetamido-2-oxo) pentyl-3- (c s-propen-1-yl) - pyrrole? din-5-carboxylic. 97A (±) - (2R.3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-oxo) pentyl-3- (c; s) t-butyl ester -propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 42A, using (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-) -butyl ester. hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 14 mg, 58%). MS: (M + H) * = 453, (M + Na) * = 475; (M-H) - = 451. 97B salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R) -2- (1-Acetam-do-2-oxo) pentyl-3- (c > s-propen-1- il) -pyrrolidine-5-carboxylic acid.

The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-oxo) pentyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl- 3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 1. 4 mg, 28%). 1H NMR (DMSO-dβ) d 8.31 (d, J = 8.3Hz, 1H), 5.40 (m, 1H), 5.19 (br t, 1H), 4.26 (t, J = 6.8Hz, 1H), 3.63 (t, J = 8.3Hz, 1H), 3.35 (m, 1H), 2.97 (m, 1H), 2.45 (m, 1H), 2.34 ( dt, J = 3.4, 7.4Hz, 1H), 2.20 (m, 1H), 1.84 (s, 3H), 1.58 (dd, J = 2, 4.3Hz, 3H), 1.43 (m, 3H), 0.82 (t, J = 7.3Hz, 3H) MS: (M-H) - = 295; (M + H) * = 297, (M + Na) * = 319.

EXAMPLE 98 Salt of trifluoroacetic acid of (+) - (2R, 3S, 5R, 1'R) -2-M-Acetamido-2-oxo) butyl-3- (cs-propen-1-yl) -pyrrolid? n-5-carboxylic acid.

FA The title compound was prepared according to the method described in Example 41C, using (+) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2-t-butyl ester - (1-acetamido-2-oxo) butyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid prepared in Example 42A in place of (±) - t-butyl ester (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxic rbon l-2- (1-acetamido-2-hydroxy) butyl-3- (c; s-propen-1 -i I ) -pyrrolidine-5-carboxylic acid (yield: 5.0 mg, 100%). 1 H NMR (DMSO-dβ) d 8.52 (d, J = 8.6Hz, 1H), 5.47 (m, 1H), 5.15 (m, 1H), 4.54 (m, 1H), 4.39 (dd, J = 11.0, 6.7 Hz, 1H), 3.84 (t, J = 9.2Hz, 1H), 3.17 (m, 1H), 2.50 (m, 1H), 2.38 (m, 1H), 2.33 (m, 1H), 1.83 (s, 3H ), 1.63 (m, 1H), 1.58 (dd, J = 6.7, 1.8Hz, 3H), 0.94 (t, J = 7.5Hz, 3H). MS: (M + H) * = 283, (M + Na) * = 305, (M-H) "= 281.

-Mea «¿¿-7- ^ Examples 99-115 The title compounds were prepared according to the method described in Examples 20 and 40-42 b but using the respective reagents.

Example 99 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R) -2- (1-Acetamido-2-oxo-2-allyl) ethyl-3- (c / 's-propen-1) -yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-de) d 8.38 (d, J = 8.5 Hz, 1 H), 5.73 (m, 1 H), 5.37 (, 1 H), 5.05 (m, 3 H), 4.32 (t, J = 7.9Hz, 1H), 3.90 (m, 1H), 3.49 (m, 1H), 3.13 (m, 2H), 2.98 (m, 1H), 3.18 (, 1H), 1.78 (s, 3H) ), 1.51 (dd, J = 5.5, 1.2Hz, 3H), 1.44 (m, 1H). MS: (M + H) * = 295, (M-H) - = 293 Example 100 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R) -2- (1-Acetamido-2-oxo-3-methyl) butyl-3-v? Nil-p? Rrol¡din -5-carboxylic acid] H NMR (DMSO-dβ) d 8.64 (d, J = 8.5Hz, 1H), 5.59 (m, 1H), 5.08 (d, J = 17 1Hz, 1H), 502 (d, J = 9 8Hz, 1H), 465 (t, J = 86Hz, 1H), 4 32 (m, 1H), 3 82 (t, J = 9.2Hz, 1H ), 2 82 (m 2H), 2 36 (m, 1H), 1.83 (s, 3H), 1 80 (m, 1H), 1.03 (d, J = 67Hz, 3H), 0.97 (d, J = 67Hz) , 3H) MS: (M + H) * = 283, (M + Na) * = 305, (MH) - = 281.

Example 101 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R) -2- (1-Acetamido-2-oxo) propyl-3-vinyl-pyrrolidine-5-caboxic acid 1H NMR (DMSO-de) d 8.96 (d, J = 79Hz, 1H), 5.71 (m, 1H), 5.27 (d, J = 17.7Hz, 1H), 5.17 (d, J = 11. OHz, 1H) , 4.38 (m, 1H), 4.29 (m, 1H), 381 (m, 1H), 2.61 (m, 1H), 2.22 (m, 1H), 2.13 (s, 3H), 2.01 (s, 3H), 1 24 (m, 1H). MS: (M + H) * = 255, (M + Na) * = 277, (M-H) "= 253.

Example 102 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R) -2- (1-Acetami o-2-oxo) butyl-3-vinyl-pyrrole d-5-carboxyl co 1H NMR (DMSO-d6) d 861 (d, J = 8 5Hz, 1H), 5.60 (m, 1H), 5 10 (d, ag ^^^^ ^ J = 17.7Hz, 1H), 5.03 (dd, J = 10.4, 1.2Hz, 1H), 4.54 (t, J = 8.5Hz, 1H), 4.38 (dd, J = 11.0, 6.7Hz, 1H), 3.86 ( , 1H), 2.84 (m, 1H), 2.52 (m, 1H), 2.37 (m, 2H), 1.85 (s, 3H), 1.82 (m, 1H), 0.94 (t, J = 7 OHz, 3H) . MS: (M + H) * = 269, (M + Na) * = 291, (M-H) '= 267.

Example 103 Salt of trifluoroacetic acid acid (±) - (2R.3S.5R.1'R) -2- (1- Ace-2-oxo) pentyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO- dβ) d 8.60 (d, J = 9.7Hz, 1H), 5.60 (m, 1H), 5.07 (m, 2H), 4.65 (m, 1H), 4.54 (m, 1H), 4.38 (m, 1H), 3.86 (m, 1H), 2.84 (m, 1H), 2.45 (m, 1H), 2.36 (m, 1H), 1.86 (s, 3H), 1.82 (m, 1H), 1.47 (m, 2H), 0.87. (t, J = 5.8Hz, 3H). MS: (M + H) * = 283, (M + Na) * = 305, (M-H) "= 281.

Example 104 Salt of the acid trifluoroacetic acid (±) - (2R.3S.5R.1'R) -2- (1- Acetate mi do-2-hydroxy) ethyl-3- vi or I- pyrrole id i n- 5-ca rboxylic 1H NMR (DMSO-d6) d 8.00 (d, J = 9.9Hz, 1H), 5.63 (m, 1H), 5.08 (m, 1H), 4.98 (m, 1H), 4 35 (m, 1H), 4.25 (m, 1H), 4.08 (m, 1H), 3.55 (m, 1H), 3.45 (m, 1H), 3.38 (m, 1H), 2.83 (m, 1H), 2.33 (m, 1H), 1.78 (s, 3H). MS: (M + H) * = 243, (M + Na) + = 265, (M-H) - = 241.

Example 105 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R.2'S) -2- (1-Acetam id o-2-hydroxy)? Ropil-3- vi nil-pi rrol id in- 5-carboxylic H NMR (DMSO-de) d 7.96 (d, J = 9.7Hz, 1H), 5.74 (m, 1H), 5.12 (m, 1H), 5.03 (m, 1H), 4.27 (m, 1H) ), 3.96 (m, 1H), 3.77 (m 1H), 3.65 (m, 1H), 2.87 (m, 1H), 2.38 (m, 1H), 1.82 (s, 3H), 1.80 (m, 1H), 1.08 (d, J = 6.0Hz, 3H). MS: (M + H) * = 257, (M + Na) * = 279, (M-H) - = 255.

Example 106 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R.2'S) -2- (1-Ace tamido-2-hydroxy) buti l-3-vi or I-pyrrole? Din -5-carboxylic 1H NMR (DMSO-dβ) 67.99 (d, J = 9.0Hz, 1H), 5 75 (m, 1H), 5.13 (d, J = • Jl Má ^ 17 1Hz, 1H), 5.04 (d, J = 10.5Hz, 1H), 4.27 (t, J = 8.4Hz, 1H), 4.04 (, 1H), 3.78 (m, 1H), 3.48 (m, 1H), 2.89 (m, 1H), 2.40 (m, 1H), 1.88 (m, 1H), 1 85 (s, 3H), 1.54 (m, 1H), 1.28 (m, 1H), 0.86 (t, J = 7.2 Hz, 3H). MS: (M + H) * = 271, (M + Na) + = 293, (M-H) - = 269.

Example 107 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'S) -2- (1-Acetate mido-2-hydroxy) pentyl-3-vini l-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-dβ) d 7.99 (d, J = 9.9Hz, 1H), 5.75 (, 1H), 5.08 (m, 2H), 4.28 (m, 1H), 4.03 (m, 1H), 3.77 (m, 1H), 3.52 (m, 1H), 2.88 (m; 1H), 2.40 (m, 1H), 1.86 (s, 3H), 1.75 (m, 1H), 1.45 (m, 2H), 1.25 (m, 2H), 0.87 (t, J = 5.9Hz, 3H). MS: (M + H) * = 285, (M + Na) * = 307, (M-H) "= 283 Example 108 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-hydroxy-3-methyl) butyl-3-vinyl-pyrrolidin-5 -carboxylic acid 1H NMR (DMSO-de) d 7.97 (d, J = 9.3Hz, 1H), 5.75 (m, 1H), 5.12 (d, J = 17.1Hz, 1H), 5.04 (d, J = 11.2Hz, 1H), 4.24 (m, 1H), 4.13 (, 1H), 3.74 (dd, J = 9.8, 6.1Hz, 1H), 344 (dd) , J = 10.3, 2.0Hz, 1H), 287 (m, 1H), 2.40 (m, 1H), 1.84 (m, 1H), 1.83 (s, 3H), 1.75 (m, 1H), 0.89 (d, J = 6.8, 3H), 0.75 (d, J = 6.8Hz, 3H). MS: (M + H) * = 285, (M + Na) * = 307, (M-H) - = 283.

Example 109 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'S) -2- (1-Acetamido-2-hydroxy-2-cyclopropyl) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-de) d 7.81 (d, J = 10.0 Hz, 1 H), 5.73 (m, 1 H), 5.05 (m, 2 H), 4.39 (m, 1 H), 4.20 (m 1 H), 3.90 (, 1H), 3.61 (m, 1H), 3.08 (m, 1H), 2.86 (m, 1H), 2.42 (m, 1H), 1.85 (s, 3H), 0.88 (m, 1H), 0.45 (, 1H) , 0.35 (m, 2H), 0.11 (m, 1H). MS: (M + H) * = 283, (M + Na) * = 305, (M-H) - = 281.

Example 110 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.2'R) -2- (1-acetamido-2-h id roxi) propi l-3-vinyl-pyrrolid i n -5-carboxylic acid 1 H NMR (DMSO-de) d 7.77 (d, J = 9.7 Hz, 1 H), 5.72 (m, 1 H), 5.07 (m, 2 H), 4.40 (m, 1 H), 4.03 (m, 1 H) ), 3.95 (m 1 H), 3.57 (m, 1H), 2.86 (m, 1H), 2.43 (m, 1H), 1.88 (m, 1H), 1.84 (s, 3H), 1.04 (d, J = 6.0) Hz, 3H). MS: (M + H) * = 257, (M + Na) * = 279, (M-H) - = 255.

Example 111 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R) -2- (1-acetamido-2-hydroxy) butyl-3-vinyl-pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-dβ) 57.72 (d, J = 9.8Hz, 1H), 5.73 (m, 1H), 5.08 (d, J = 17.1Hz, 1H), 5.03 (d, J = 10.4Hz, 1H), 4.41 (m, 1H), 4.13 (m, 1H), 3.68 (m, 1H), 3.63 (m, 1H), 2.88 (m, 1H), 2.44 (m, 1H), 1.90 (m, 1H), 1.83 (s, 3H), 1.38 (m, 2H), 0.84 (t, J = 7.3Hz, 3H). MS: (M + H) * = 271, (M + Na) * = 293, (M-H) - = 269.

Example 112 Salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetam id o-2-h id roxi) pen til-3- vi nil-p 1-NMR (n-5-ca) 1H NMR (DMSO-de) 5 7.72 (d, J = 9.9Hz, 1H), 5.72 (m, 1H), 5.06 (m, 2H), 4.42 (m, 1H), 4.09 (m, 1H), 3.77 (m, 1H), 3.61 (m, 1H), 2.87 (m, 1H), 2.43 (m, 1H), 1.90 (m, 1H), 1.83 (s, 3H) ), 1.37 (m, 2H), 1.27 (m, 2H), 0.87 (t, J = 5.9Hz, 3H). MS: (M + H) * = 285, (M + Na) * = 307, (M-H) - = 283.

Example 113 Salt of trifluoroacetic acid acid (±) - (2R, 3S, 5R.1'R.2'R) -2- (1-acetamido-2-hydroxy-3-methyl) butyl-3-vinyl-pyrrolidin-5 -carboxylic 1H NMR (DMSO-d6) d 7.71 (d, J = 9.3Hz, 1H), 5.70 (m, 1H), 5.08 (d, J = 17.1Hz, 1H), 5.03 (d, J = 10.3Hz, 1H), 4.42 (m, 1H), 4.25 (m, 1H), 3.61 (m, 1H), 3.35 (dd, J = 8.3, 25Hz, 1H), 2.90 (m, 1H), 2.44 (m, 1H) , 1.92 (m, 1H), 1 82 (s, 3H), 1.58 (m 1H), 0.95 (d, J = 6.8Hz, 3H), 0.79 (d, J = 6.4Hz, 3H).

MS: (M + H) * = 285, (M + Na) * = 307, (M-H) - = 283.

Example 114 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'R.2'R) -2- (1-acetamido-2-hydroxy-2-cyclopropyl) ethyl-3-vinyl-pyrrolidin-5 -carboxylic H NMR (DMSO-dβ) d 7.94 (d, J = 9.6Hz, 1H), 5.76 (m, 1H), 5.12 (m, 2H), 4.40 (m, 1H), 4.21 (m, 1H), 3.90 (m, 1H), 3.53 (m, 1H), 3.13 (m, 1H), 2.81 (m, 1H), 2.25 (m, 1H), 1.87 (s, 3H), 0.90 (m, 1H), 0.47. (m, 1H), 0.37 (m, 2H), 0.15 (m, 1H). MS: (M + H) * = 283, (M + Na) * = 305, (M-H) - = 281.

Example 115 Salt of trifluoroacetic acid acid (±) - (2R, 3S.5R.1'R.2'R) -2- (1-acetamido-2-hydroxy-4-methyl) pentyl-3-vinyl-pyrrolidin-5 -carboxylic 1 H NMR (DMSO-d 6) d 7.71. d, J = 9.7Hz, 1H), 5.83 (m, 1H), 5.06 (d, J = 17. 1Hz, 1H), 5.02 (d, J = 10.3Hz, 1H), 4.41 (, 1H), 4.06 (m, 1H), 3.83 (m, 1H), 3.59 (t, J = 8.8Hz, 1H), 2.84 (m, 1H), 2.42 (m, 1H), 1.90 (m, 1H), 1 82 (s, 3H), 1 71 (m, 1H), 1 34 (m, 1H), 1.07 (m, 1H), 0.89 (d, J = 6.8Hz, 3H), 0.86 (d, J = 6.3Hz, 3H) MS (M + H) * = 299, (M + Na) * = 321, (MH) - = 297.

Example 116 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R) -2- (1-acetamido-2-hydroxy-2-methyl) propyl-3-v? Nyl- pyrrolidine-5-carboxylic 116A (±) - (2R, 3S.5R.1'R) -f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-methyl) propyl-3-v acid t-butyl ester Nil-pyrrolidine-5-carboxylic acid. T-butyl ester of (+) - (2R, 3S, 5R, 1'R) -f- bu toxic rb onyl 2- (1 -acetamido-2-oxo) propyl-3-vinyl-pyrrolidin was reacted -5- carboxylic acid (11 mg, 0.027 mmol) with methyl magnesium bromide (3 M) (0.05mL, 0.134 mmol) in THF (2 mL) at 25 ° C for 2 hours. The reaction was set with saturated aqueous ammonium chloride (2 mL) and water (2 mL), followed by extraction using dichloromethane (2 X 5 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on column on silica gel using 2/1: ethyl acetate / hexane to give the title compound (yield - 1.9 mg, 17%). MS: (M + H) * = 427, (M-H) - = 425 116B Salt of trifluoroacetic acid of (±) - (2R.3S, 5R.1'R) -2- (1-acetamido-2-hydroxy-2-methyl) propyl-3-vinyl-pyrroli in-5 -carboxylic The title compound was prepared according to method 5 that is described in Example 41C, using (±) - (2 R, 3S, 5 R, 1'R) -1 -f t-butyl ester -butoxycarbonyl-2- (1 -acetamido-2-hydroxy-2-methyl) propyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (±) - (2 R, 3S, 5) t-butyl ester R, 1'R, 2'S) - 1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 10 1.6 mg, 99%). 1 H NMR (DMSO-de) d 7.70 (d, J = 9.9Hz, 1H), 5.75 (m, 1H), 5.02 (m, 2H), 4.37 (m, 1H), 4.15 (m, 1H), 3.61 ( m, 1H), 2.78 (m, 1H), 2.41 (m, 1H), 1.81 (s, 3H), 1.20 (s, 3H), 1.12 (s, 3H) MS: (M + H) * = 271, (M + 23) * = 293, (MH) - = 269 15 Example 117 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R) -2- (1- acetamido-2-hydroxy) -2-ethyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid 117A (±) - (2R, 3S, 5R, 1'R) -f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-ethyl) butyl-3-vinyl-pyrrolid acid t-butyl ester ? n-5-carboxylic acid.

The (±) - (2R, 3S, 5R, 1'R) -f-butoxycarbonyl-2- (1-acetamido-2-oxo) butyl-3-vinyl-pyrrole acid t-butyl ester was reacted? din-5-carboxylic acid (37mg, 0.087 mmol) with ethyl magnesium bromide (3M) (0.15mL, 0.44mmol) in THF (5 mL) at 25 ° C for 2 hours The reaction was set with saturated aqueous ammonium chloride (5 mL) and water (5 mL), followed by extraction using dichloromethane (2 X 10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2/1: ethyl acetate / hexane to give the title compound (yield: 14 mg, 35%). MS: (M + H) * = 455, (M-H) - = 453 117A Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R) -2- (1-acetamido-2-hydroxy-2-yl) butyl-3-vinyl-pyrrolidin Carboxylic acid The title compound was prepared according to the method described in Example 41c, using (±) - (2R, 3S, 5R, 1'R) -1-f- t-butyl ester butoxycarbonyl-2- (1-aceta-ido-2-hydroxy-2-ethyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 5.8 mg, 98%). 1 H NMR (DMSO-dβ) 5 7.62 (d, J = 9.6HZ, 1H), 5.75 (m, 1H), 5.03 (m, 2H), 4.39 (m, 1H), 4.31 (m, 2H), 3.87 (m, 1H), 3.38 (m, 1H), 2.88 (m, 1H), 240 (m, 1H), 1.83 (s, 3H ), 1.55-1.30 (m, 4H), 0.86 (m, 6H) MS. (M + H) * = 299, (M-H) - = 297 EXAMPLE 118 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'S) -2- (1-acetamido) allyl-3- (cjs-propen-1-? L) -pyrrolidine-5-carboxylic acid 118A (±) - (2R.3S, 5R.1'S) -1-f-butoxycarbonyl-2- (1-acetamido) allyl-3- (cs-propen-1-yl) -pyrrolidin- acid t-butyl ester 5-carboxylic acid The title compound was prepared according to the method described in Example 20K, using acid t-butyl ester (±) - (2 R, 3S, 5 R, 1'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-f ormyl) meti I- 3- (c; 's-propen-1) -yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl t-butyl ester 3-formyl-pyrrolidine-5-carboxylic acid (yield: 15.3 mg, 61. 4%). MS: (M + H) * = 409. 118B Salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1'S) -2- (1-acetamido) allyl-3- (cs-propßn-1-yl) -pyrrolidine-5-carboxylic acid The compound of The title was prepared according to the method described in Example 41C, using t-butyl ester of (+) - (2R, 3S, 5R, 1'S) - 1-f-butoxycarbonyl-2- (1 - acetamido) al? l-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 13.1 mg, 100%). 1 H NMR (DMSO-d 6): 51.58 (dd, 3H), 1.74 (dt, 1H), 1.88 (s, 3H), 2.41 (dt, 1H), 3.17 (m, 1H), 3.56 (dd, 1H), 4.35 (dd, 1H), 4.70 (dd, 1H), 5.22-5.30 (m, 3H), 5.51 (m, 1H), 5.82 (m, 1H), 8.15 (d, 1H), 9.18 (br s, 2H) ). MS: (M + H) * = 253.

EXAMPLE 119 Salt of tpfluoroacetic acid of (+) - (2R, 3S, 5R.1'S) -2- (1-acetamido-2- (cs and frans) buten- 1 -ID-3- (c / s) - pro pen- 1 -yl) -pi rrol idi n-5-carboxylic 119A (±) - (2R.3S.5R.1'S) t-butyl ester -1-f-butoxycarbonyl-2- (1 -acetam ido-2- (c / sv fraps) buten-1-yl) - 3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 20K, using t-butyl ester of (±) - ( 2R, 3S, 5R, 1'S) - 1-f-butoxycarbonyl-2- (1 -acetamido-2-formyl) methyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester and bromide of ethyltriphenylphosphonium instead of methyltriphenylphosphonium bromide (yield: 12.4 mg, 48.2%). MS: (M + H) * = 423 119B Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'S) -2- (1-acetamido-2- (c / s and fra / 7s) buten-1-yl) -3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5 R, 1'S) -1-f-butoxy carbon i-2- (1 -acetamido-2- (c / 's and trans) buten t-butyl ester. -1-yl) -3- (cs-propen-1-yl) -p? Rrolidin-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 11.8 mg, 100%). 1 H NMR (DMSO-de): 51.63 (dd, 3H), 1.66 (dd, 3H), 1.74 (m, 1H), 1.88 (s, 3H), 2.41 (dt, 1H), 3.17 (m, 1H), 3.50 (dd, 1H), 4.34 (dd, 1H), 4.95 (m, 1H), 5.23 (m, 1H), 5.39 (m, 1H), 5.53 (m, 1H), 5.68 (m, 1H), 8.21 (d, 1H), 9.18 (br s, 2H). MS: (M + H) * = 267 EXAMPLE 120 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'S) -2- (1-acetamido-3,3-dimethyl) allyl-3- (c / s-propen-1? ) -pyrrolidine-5-carboxylic acid 120A t-butyl ester of the acid (±) - (2R.3S.5R.1'S) -1-f-butoxycarbonyl-2- (1 -acetamido-3,3-d imethyl) allyl-3- (c / s-propen -1-yl) -pyrrol idin-5-carboxylic acid The title compound was prepared according to the method described in Example 20K, using (±) - (2 R, 3S, 5 R) t-butyl ester , 1'S) - 1-f-butoxycarbonyl-2- (1 -acetam-ido-2-p-oryl) methyl-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxyl? Co instead of t -butyl ester of acid (±) - (2R, 3R, 5R, 1"S) -1-f-butoxycarbonyl-2- (1 -acetamido-3-methyl) butyl-3-formyl-pyrrolidin-5- carboxylic acid and isopropyltriphenylphosphonium bromide in place of methyltriphenylphosphonium bromide (yield: 8.2 mg, 25.9%) MS: (M + H) * = 437 120B Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'S) -2- (1-acetamido-3,3-dimethyl) allyl-3- (cs-propen-1-yl) -pyrrolidin-5 -carboxylic The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-3,3-dimethyl) allyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1) t-butyl ester 'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 7.5 mg, 100%). H NMR (DMSO-d6): 51.53 (dd, 3H), 1.57 (s, 3H), 1.61 (s, 3H), 1.66 (m, 1H), 1.77 (s, 3H), 2.32 (dt, 1H), 3.07 (m, 1H), 3.39 (dd, 1H), 4.26 (m, 1H), 4.75 (m, 1H), 5.07 (d, 1H), 5.15 (m, 1H), 5.44 (m, 1H), 8.06 (d, 1H). MS: (M + H) * = 281.

EXAMPLE 121 Salt of the trifluoroacetic acid of (±) - (2R.3S.5R.1'S) -2- (1-acetam id 0-2- (os and fraps) penten-1-yl) -3- ( c / s-propen-1-i0-pyrrolidin-5-carboxylic acid 121A (±) - (2R, 3S, 5R, 1'S) t-butyl ester-1-f-butoxycarbonyl-2- (1-acetamido-2- (c / syfrans) penten-1-yl) -3 - (c s-propen-1-yl) -pyrrolid i-5-carboxylic acid The title compound was prepared according to the method described in the Example using (±) - (2 R) t-butyl ester , 3S, 5 R, 1'S) - 1-f- bu toxi carbon il-2- (1 -ace tamido-2-f ormil) meti I-3- (c s -propen-1-yl) -pyrrolidin- 5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine t-butyl ester -5-carboxylic acid and n-butyltriphenylphosphonium bromide in place of methyltriphenylphosphonium bromide (yield: 21.0 mg, 66.2%). MS: (M + H) * = 437. 121B Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1 'S) -2- (1-acetamido-2- (c / s and frans) penten-1-yl) -3- (cs- propen-1-? l) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5 R) t-butyl ester , 1'S) -1-f-butoxycarbonyl-2- (1 -acetam-ido-2- (cs and trans) penten-1-yl) -3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid in Place of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 16.0 mg, 98.1%). 1 H NMR (DMSO-d 6): d 0.93 (t, 3 H), 1.62 (dd, 3 H), 1.75 (m, 1 H), 1.87 (s, 3 H), 2.07 (m, 2 H). 2.40 (m, 1H), 3.17 (m, 1H), 3.50 (m, 1H), 4.34 (m, 1H), 4.94 (m, 1H), 5.23 (m, 1H), 534 (m, 1H), 5.53 (m, 1H), 5.58 (m, 1H), 8.24 (d, 1H), 9.25 (br s, 2H). MS: (M + H) * = 281.

Example 122 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'S) -2- (1-acetami or-4-hydroxy-2- (c) sv fraps) buten-1-yl) -3 - (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 122A (±) - (2R.3S.5R.1'S) t-butyl ester-1-f-butoxycarbonyl-2- (1 -acetam-do-4- (f-butyldimethylsilyloxy) -2- (c / s) rans) buten-1-yl) -3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in the Example using t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-formyl) methyl-3- (c / 's-propen-1-yl) - pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-t-butyl ester -pyrrolidine-5-carboxylic acid and 4- (f-butyldimethylsilyloxy) -butyltriphenylphosphonium bromide in place of methyltriphenylphosphonium bromide (yield: 23.1 mg, 66.9%). MS: (M + H) * = 567. 122B Salt of the tpfluoroacetic acid of (+) - (2R.3S, 5R, 1 'S) -2- (1-acetamido-4-hydroxy-2- (c / sv frans) buten-1-yl) -3 - (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R) t-butyl ester , 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1 -aceta mid o-2- (c / 's and trans) -4-hydroxy-butenyl-2-yl) -3- (cs-propen -1-? L) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-fb or toxy carboni l-2- ( 1-acetamyl-2-h id rox?) Buyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 16.9 mg,> 100%). 1 H NMR (DMSO-d 6): 51.67 (dd, 3 H), 1.78 (dt, 1 H), 1.91 (s, 3 H), 2.44 (m, 1 H), 2.50 (m, 1 H), 2.56 (m, 1 H), 2.65 (, 1H), 323 (m, 1H), 3.54 (m, 1H), 4.40 (, 1H), 4.47 (m, 2H), 5.01 (, 1H), 5.26 (m, 1H), 5.54 (m, 2H), 5.63 (m, 1H), 8.32 (d, 1H), 9.27 (br s, 2H) MS: (M + H) * = 297.

«E * a-t;« alfc? Example 123 (±) - (2R, 3S, 5R.1 'S) -2- (1-Acetamido) butyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride 123B (±) - (2R, 3R, 5R) -1-Benzyl-2-vinyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester. (±) - (2R, 3R, 5R) -1-Benzyl-2-vinyl-3-hydroxymethyl-pyrrolidin-5-carboxylic acid t-butyl ester (30.8 g, 97.1 mmol) was reacted with t-butyl chloride. -butyldiphenylsilyl (49.5 L, 190.4 mmol) and imidazole in dichloromethane (650 mL) at 0 ° C for 1 hour. The reaction was set with methanol, followed by extraction with dichloromethane (600 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 2/1: chloroform / hexane to give the title compound (yield: 52. 9 g, 98%). 1H NMR (CDCU) d 7.62-7.67 (m, 4H), 7.32-7.44 (m, 6H), 7.25-7.30 (m, 5H), 5.58-5.72 (m, 1H), 5.06-5.14 (m, 2H), 3.90 (d, 1H), 3.72-3.78 (m, 1H), 3.58-3.68 (m, 2H), 3.44 -3.52 (m, 2H), 2.26-2.40 (m, 1H), 2.10-2.23 (m, 1H), 1.68-1.78 (m, 1H), 1.38 (s, 9H), 1.03 (s, 9H).

MS: (M + H) * = 556 123B (±) - (2R, 3R.5R.1'RS) -1-Benzyl-2- (1,2-dihydroxy) ethyl-3-f-butyldiphenylsiloxyl-methyl-pyrrolidin- t-butyl ester 5-carboxylic acid The (±) - (2R, 3R, 5R) -1-benzyl-2-vinyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester (22.7 g, 41 mmol) was reacted with Os04 (4%) (2.5 mL, 0.7 mol.%) And N-methyl morpholine N-oxide (18.5 g, 2.77 eq.) In acetone (500 mL) and water (60 mL) for 48 h at room temperature. The reaction was set with 10% aqueous Na 2 S 2 3 3 (200 mL). The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate / water. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 35% ethyl acetate / hexane to give the title compound (yield: 11 g, 55%). t H NMR (DMSO-de) d 7.58-7.63 (m, 5H), 7.40-7.48 (m, 7H), 7.20-7.35 (m, 3H), 4.41-4.45 (m, 2H), 3.98 (d, 1H ), 3.75-3.84 (m, 2H), 3.50-3.68 (m, 2H), 3.4-3.46 (m, 1H), 3.16-3.25 (m, 1H), 2.97-3.0 (m, 1H), 2.09-2.28 (m, 1H), 1.62-1.89 (m, 1H), 1.34-1.39 (m, 1H), 1.30 (s, 9H), .98, .96 (2s, 9H). MS: (M + H) * = 590 TB 123C t-butyl ester of (+) - (2R, 3R.5R, 1 'RS) -2- (, 2-dihydroxy) et? 1 -3-f-butyldiphenylsilyloxymethyl I-pyrro l? Din-5- carboxylic The (±) - (2R, 3R, 5R, 1'RS) -1-benzyl-2- (1, 2-dihydroxy) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidin- (t) -butyl ester was reacted 5-carboxylic acid (11 g, 18.7 mmol) under 1 atmosphere of hydrogen with 20% Pd (OH) 2 / C (5 g) and in ethanol (40 mL) was stirred vigorously for 2.5 days at room temperature. The reaction was filtered and the catalyst was washed with methanol (3x30 mL). The filtrate was evaporated in vacuo to give the title compound as an oil (yield: 8 g, 94%) 123D (+) - (2R, 3R, 5R, 1'R) -1-f-butoxycarbonyl-2- (1,2-dihydroxy) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidin-5-butyl ester carboxylic The title compound was prepared according to the method described in Example 40D, using (+) - (2R, 3R, 5R, 1'RS) -2- (1,2-dihydroxy) t-butyl ester ) ethyl-3-f-butyl-phenylsilyloxymethyl-pyrrolidine-5-carboxyl? co instead of (2R, 3R, 5R, 1'RS) -2- (1, 2-dihydroxy) ethyl-3-acetoxy? l-pyrrolidine-5-carboxylic acid. The residue was purified by column chromatography on silica gel using % ethyl acetate / hexane to give the title compound (yield: 20.5 g, 60%). 1 H NMR (DMSO-de) d 7.57-7.60 (m, 4H), 738-7.48 (, 6H), 4.85.4.77 (2d, 1H), 4.45-4.50 (m, 1H), 402-410 (m, 1H ), 3.80-3.95 (m, 1H), 3.73.3.68 (2s, 1H), 3.45-3.67 (m, 2H), 3.18-3.28 (m, 2H), 2.36-2.46 (m, 2H), 1.86,1.70 (2d, 1H), 1.40.1.35 (2s, 9H), 1 32.1.26 (2s, 9H), 1.0.0.98 (2s, 9H). MS: (M + H) * = 600 123E (±) - (2R, 3R.5R.1'R) -1-f-butoxycarbonyl-2- (1-methanesulfonyloxy-2-acetoxy) ethyl-3-f-bu ti Id-butyl ester if eni Isil i loxi meti I-pyrrolidin-5-carboxylic acid. T-butyl ester of (+) - (2R, 3R, 5R, 1'R) -1-t-bu toxic acid rbonyl-2- (1,2-dihydroxy) ethyl-3-f-butyldiphenylsilyloxymethyl- was reacted pyrrolidine-5-carboxylic acid (20.5 g, 34.2 mmol) with acetic anhydride (16.1 mL, 171 mmol) and tetylamine (47.7 mL, 342 mmol) in dichloromethane (360 mL) at 0 ° C for 16 h. The reaction was treated with methanol (35 mL) for 10 minutes and diluted with dichloromethane (1300 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was reacted with methanesulfonyl chloride (4.0 L, 51.3 mmol) and triethylamine (14.3 mL, 103 mmol) in dichloromethane (350 mL) at 0 ° C for 1.5 hours. The reaction was set with water (300 mL) and serdiluted with dichloromethane (1200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated to vacuum. The residue was purified by chromatography on silica gel using 30% ethyl acetate / hexane to give the title compound (yield: 23.8 g, 97%). H NMR (DMSO-d6) 67.58-7.62 (m, 4H), 7.38-7.50 (m, 6H), 5.12-5.26 (2m, 1H), 4.06-4.25 (m, 3H), 4.00 (d, 1H), 3.46-3.68 (m, 2H), 3.20.3.18 (2s, 3H), 2.40-2.48 (, 1H), 2.02.1.99, (2s, 3H), 1.68-1.88 (m, 1H), 1.42.1.36 (2s) , 9H), 1.31.1.25 (2s, 9H), 1.00.0.98 (2s, 9H). MS: (M + H) * = 720, (M + NH4) * = 737 TBDPSO- P'Bu ^ H R Bnorc. Y ^ 123F (±) - (2R, 3R, 5R.1'S) -1-f-Butoxycarbonyl-2-oxirani-3-f-butyldiphen-lysilyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester. Reacting t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-f-bu toxic rbon il-2- (1-methanesulf oni loxi-2-acetoxy) ethyl-3-f -butyldif in il-silyloxymethyl-pyrrolidine-5-carboxylic acid (23.8 g, 33.1 mmol) with potassium carbonate (10.1 g, 66.2 mmol) in methanol (160 mL) and THF (160 mL) at 25 ° C for 18 hours. The reaction was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine, dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 25% ethyl acetate / hexane to give the title compound, as oil (yield: 16.7 g, 87%). 1H NMR (CDCU) d 7.60-7.68 (m, 4H), 7.32-7.45 (m, 6H), 4.02-4.28 (, 2H), 3.67-3.78 (m, 1H), 3.52-3.62 (m, 1H), 3.0-3.08 (m, 1H), 2.68-2.75 (m, 1H), 2.47-2.52 (m, 3H), 1.80-1.90 (m, 1H), 1.48.1.42 (2s, 9H), 1.37.1.35 (2s) , 9H), 1.07.1.03 (2s, 9H). MS: (M + H) * = 582 HO- P'Bu N ^ 'H R Bnorc. if 123G t-butyl ester of (±) - (2R.3R, 5R.1'S) -1-f-butoxycarbonyl-2-oxy-ranyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid. Reacted t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarboni l-2-oxira or l-3-f-butylidif eni Isyl iloxy meti I-pyrrole n-5-carboxylic acid (4.17 g, 7.2 mmol) with tetrabutylammonium fluoride (1M) (14 mL, 14.0 mmol) in THF (7 mL) for 20 minutes at 0 ° C then for 1.5 hours at 25 ° C. The reaction was concentrated in vacuo, the residue was dissolved in ethyl acetate and washed with pH 7.0 buffer and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexane to give the title compound, as an oil (yield: 2.4 g, 97%). 1 H NMR (DMSO-de) d 4.72-4.78 (m, 1H), 3.94-4.05 (m, 2H), 3.35-3.47 (m, 1H), 3.18-3.28 (m, 1H), 3.03-3.08 (m, 1H), 2.63-2.73 (m, 1H), 2.37-2.44 (m, 1H), 2.30-2.36 (m, 1H), 2.08-2.20 (, 1H), 1.58-1.75 (m, 1H), 1 40 (s, 9H), 1 37.1.34 (2s, 9H) MS (M + H) * = 344, (M + Na) * = 366 0 = 7 P'Bu H Bnoc if 123H t-butyl ester of (±) - (2R, 3R.5R.1'S) -1-f-butoxycarbonyl-2-oxiranyl-3-formyl-pyrrolidin-5- carboxylic T-butyl ester of (+) - (2R, 3R, 5R, 1'S) -1-f- bu toxic rbonyl-2-oxira nyl-3-hydroxy-methyl-pyrrole-din-5-carboxylic acid was reacted. (2.4 g, 7.0 mmol) and triethylamine (3.9 mL 28.0 mmol) in diechloromethane (70 mL) at 0 ° C with the sulfur trioxide / pyridine complex (3.35 g, 21.0 mmol) in dimethylsulfoxide (21 mL) by drip followed by reaction for an additional 3 hours. The reaction was set with water (50 mL) and diluted with ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to give the title compound (yield: 2.2 g,). 1 H NMR (DMSO-dβ) (rotamers) d 9.58 and 9.56 (2s, 1H), 4.70 and 4.53 (2m, 1H), 3.96 (dd, J = 1.4, 9.2 Hz, 1H), 3.25-3.20 (m, 1H ), 2.91 (m, 1H), 2.71 (, 1H), 2.50-2.28 (m, 3H), 1.42, 1.37, 1.34, and 1.30 (4s, 18H) MS: (MH) - = 340 * ¿~ 1231 (±) - (2R.3S.5R.1'S) -1-t-butoxycarbonyl-2-oxiranyl-3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester. Triphenylphosphoranylidenemethylllide (17.6 mmol) was prepared by reacting methyltriphenylphosphonium bromide (12.63 g, 35.4 mmol) and potassium tert-butoxide (1M) (17.6 mL, 17.6 mmol) in THF (70 mL) for 1 hour at 25 ° C. (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2-oxiranyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester (2.2 g, 6.5 mmol) was added THF (10 mL) was added to the preceding solution at 0 ° C and stirred for 0.5 hour. The reaction was set with saturated ammonium chloride (50 mL) and diluted with ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexane to give the title compound (yield: 2 g, 84%). 1 H NMR (DMSO-de) 55.80-5.95 (m, 1H), 5.08 (d, 1H), 4.94-5.04 (1H), 4.00-4.07 (m, 1H), 3.59.3.90 (2t, 1H), 3.07- 3.16 (m, 1H), 2.73-2.81 (m, 1H), 2.65-2.72 (m, 1H), 2.35-2.48 (m, 1H), 1.59-1.76 (m, 1H), 1.42 (s, 9H), 1.38.1.35 (2s, 9H). MS: (M + H) * = 340 123J (±) - (2R.3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-methanesulfonyloxy-3-azido) ethyl-3-vinyl-pyrrolidin-5 acid t-butyl ester carboxyl? co.

The (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbon-l-2-oxiranyl-3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester (1.72 g, 5.1 mmol) was reacted. ) and ammonium chloride (1.36 g, 25.4 mmol) in ethanol (45 mL) and water (5 mL) with lithium azide (1.2 g, 24.5 mmol) for 7 hours at 50 ° C. The reaction was concentrated in vacuo and it was diluted with ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue (2.15 g) was dissolved in dichloromethane (50 mL), reacted with methanesulfonyl chloride (0.8 mL, 10.2 mmol) and triethylamine (2.8 mL, 20.4 mmol) for 0.5 hours at 0 ° C. The reaction was Fractioned with aqueous sodium bicarbonate (50 mL) and diluted with ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexane to give the title compound (yield 1.87 g, 80%). 1 H NMR (DMSO-de) d 5.77-5.98 (m, 1H), 4.94-5.11 (m, 3H), 412-4.19 (m, 1H), 3.99-4.06 (m, 1H), 3.66.3.71 (2d, 1H), 325.3.22 (2s, 3H), 292-3.02 (m, 1H), 2.55-263 (m, 1H), 1.68-1.82 (m.1H), 1.45.1.42 (2s, 9H), 1.38, 1.36 (2s, 9H) MS. (M + H) * = 461 P'Bu HN; N ^ H Rnr. lf 123K (±) - (2R, 3S, 5R, 1'S) -1-f-Butoxycarbonyl-2-aziridinyl-3-vinyl-pyrrolidin-5-carboxylic acid t-butyl ester. T-butyl ester of (±) - (2R, 3S, 5R, 1 'S) -1-f-bu toxicarbo or l-2- (1-methanesulfonyl oxy-3-azido) was reacted -3- saw neither I-pyrrolidine-5-carboxylic acid (2.12 g, 46 mmol) with triphenylphosphine (1.81 g, 6.9 mmol) in THF (30 L) and water (7.5 mL) at 65 ° C for 1 hour. The reaction was concentrated in vacuo and redissolved in ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using methanol in 4% dichloromethane to give 2 g of the crude title compound containing approximately 60% product and 40% Ph3PO which was used directly for acylation. 1 H NMR (DMSO-de) d 5.78-5.5.98 (m, 1H), 4.12 (d, 1H), 3.42.3.19 (2d, 1H), 2.53-2.73 (m, 2H), 2.00-2.15 (m, 1H), 1.68-1.76 (m, 1H), 1.62-1.68 (m, 1H), 1.41 (s, 9H), 1.37.1.36 (2s, 9H). MS: (M + H) * = 339, (M + Na) * = 361 P'Bu AcN N ^ H R r. lf 123L t-butyl ester of (±) - (2R.3S.5R, 1'S) -1-f-butoxycarbonyl-2- (N-acetylaziridinyl) -3-vinyl-pyrrolidine-5-carboxylic acid. The (+) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2-aziridinyl-3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester (1.03 g, 3. 1 mmol) with acetic anhydride (.42 mL, 4.7 mmol) and triethylamine (1.3 mL, 9.3 mmol) in dichloromethane (30 mL) at 25 ° C for 1 hour.

The reaction was set with water (50 mL) and diluted with ethyl acetate (200 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 20% ethyl acetate / hexane to give the title compound (yield: .75 g, 64%). H NMR (DMSO-de) d 5.78-5.98 (m, 1H), 5.05 (d, 1H), 4.98.4.94 (2d, 1H), 4.12-4.20 (m, 1H), 354.3.42 (2dd, 1H) , 2.54-2.98 (m, 3H), 2. 40.2.49 (2d, 1H), 2.15.2.19 (2d, 1H), 2.02.2.04 (2s, 3H), 1.68-1.82 (m, 1H), 1.42 (s, 9H), 1.48.1.45 (2s, 9H). MS: (2M + Na) * = 783. 123M (±) - (2R.3S.5R.1, S) -1-f-butoxycarbonyl-2- (1-acetami o) butyl-3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester. To a suspension of copper bromide (l) / dimethyl sulfide complex (0.051 g, 0.248 mmol) in THF (1.0 ml) at 0 ° C was added ethylmagnesium bromide (1M) (1.0 ml, 1.0 mmol) in THF. After stirring for 10 minutes at 0 ° C, a portion of this solution (0.60 ml) was added by gpteo to a solution of t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'S) -1- / -butoxycarbonyl-2- (N-acetylaziridinyl) -3-vinyl-pyrrolidine-5-carboxylic acid (0.020 g, 0.053 mmol) in THF (0.40 ml) at -78 ° C. After stirring for 20 minutes at -78 ° C , the reaction was warmed to 0 ° C and stirred for 30 minutes. The reaction was set with saturated ammonium chloride (1.0 mL) and diluted with ethyl acetate (10 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using a gradient of 0-75% ethyl acetate / hexane to give the title compound (yield: 0.004 g, 19%). 1 H NMR (DMSO-dβ) (rotamers) d 7.48 (d, J = 9.5Hz, 1H), 5.98-5.80 (m, 1H), 5.00-4.90 (m, 2H), 4.45-4.25 (m, 1H), 3.96-3.91 (m, 1H), 3.60-3.57 and 3.53-3.50 (2m, 1H), 2.91-2.76 (m, 1H), 2.59-2.42 (m, 1H), 1.80 (s, 3H), 1.73-1.59 (, 1H), 1.42 and 1.41 (2s, 9H), 1.40-1.15 (m, 4H), 1.37 and 1.34 (2s, 9H), 0.89-082 (m, 3H). MS: (M-H) "= 409, (M + H) * = 411. 123N Salt of (±) - (2R.3S.5R.1'S) -2- (1-acetamido) butyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloric acid The title compound was prepared from according to the method described in Example 1K, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetated) butyl-3-t-butyl ester -vinyl-pyrrolidine-5-carboxylic acid instead of (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 3.1 mg, 99 %). 1H NMR (DMSO-de) d 8.11 (d, J = 7.3Hz, 1H), 5.76-5.69 (m, 1H), 5.16 (d, J = 17.1Hz, 1H), 5.07 (dd, J = 1.5, 10.3 Hz, 1H), 4.30 (dd, J = 7.3, 9.8Hz, 1H), 4.13 (m, 1H), 3.50 (dd, J = 5.9, 9.8Hz, 1H), 2.90 (m, 1H), 2.39 (m , 1H), 1.92-1.85 (m, 1H), 1.87 (s, 3H), 1.52-1.18 (m, 4H), 0.85 (t, J = 7.3, 3H) MS: (MH) - = 253, (M + H) * = 255 Examples 124-130 AcN T H R Brovc > The following title compounds were prepared in two steps, according to the methods described in Examples 123M and B-jfct .. 123N, the indicated reagents and their respective methods being replaced instead of diethylcuprate and their preparation in Example 123M corresponding to step 1.

Example 124 Salt of (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido) hexyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloric acid The organocuprate reagent was prepared from a reagent Grignard and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 123M, but using 2M butylmagnesium chloride instead of 1M ethylmagnesium bromide. 1H NMR (MeOD-d3) d 5.82-5.70 (m, 1H), 5.29 (d, J = 17.0Hz, 1H), 5.17 (dd, J = 1.3, 10.2Hz, 1H), 4.35 (dd, J = 7.5 , 10.2Hz, 1H), 4 \ 19 (m, 1H), 3.65 (dd, J = 3.4, 9.8Hz, 1H), 3.01 (m, 1H), 2.55 (m, 1H), 2.08-1.97 (m, 1H), 2.04 (s, 3H), 1.62-1.31 (m, 8H), 0.91 (t, J = 6.4Hz, 3H) MS: (MH) - = 281, (M + H) * = 283 Example 125 bHWlKSi.

Salt of (+ - (2R.3S, 5R, 1'S) -2- (1-Acetamido-4-methyl) pentyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloric acid The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 123M, but using iso-butylmagnesium chloride in place of ethylmagnesium bromide. 1H NMR (MeOD -d3) d 5.83-5.71 (m, 1H), 5.29 (dd, J = 0.7.17.0Hz, 1H), 5.17 (dd, J = 0.7, 10.2Hz, 1H), 434 (dd, J = 7.5, 10.2 Hz, 1H), 4.15 (, 1H), 3.66 (dd, J = 3.4, 9.8Hz, 1H), 3.01 (m, 1H), 2.55 (m, 1H), 2.08-1.97 (m, 1H), 2.04 ( s, 3H), 1.65-1 10 (m, 5H), 0.91 (d, J = 6.4Hz, 3H), 0.91 (d, J = 6.5Hz, 3H) (M + H) * = 283 Example 126 Salt of acid hydrochloric acid (±) - (2R.3S, 5R, 1'S) -2- (1-acetamido-3,3-dimethyl) butyl-3-vinyl-pyrrolidine-5-carboxylic acid The reagent Organocuprate was prepared from a reagent Grignard and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 123M, but using 1M of tert-butylmagnesium chloride instead of 1M of ethylmagnesium bromide. 1H NMR (MeOD-d3) d 5.84-5.71 (m, 1H), 5.31 (d, J = 17.0Hz, 1H), 5.19 (d, J = 10.2Hz, 1H), 4.39-4.33 (m, 2H), 3.66 (dd, J = 3.4, 9.8Hz, 1H), 3.02 (m, 1H), 2.57 (m, 1H), 2.08-1.97 (m, 1H), 2.02 (s, 3H), 1.55 (dd, J = 9.5, 14.6Hz, 1H), 1.42 (dd, J = 1.4, 14.6Hz, 1H), 0.95 (s, 9H) (M + H) * = 283 Example 127 Salt of (±) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2-phenyl) -ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloric acid Lithium diphenyl-caprate was prepared in accordance with the method described by Lipshutz, BH in Organometallics in Synthesis; Sclosser, M., Ed .; Wiley and Sons: New York, 1994; p.292. This cuprate was used according to the methods described in Example 123M, but using lithium diphenylcycloup instead of the Grignard-derived diethylcuprate complex. 1 H NMR (MeOD-d 3) d 7.35-7.21 (m, 5H), 5.87-5.75 (m, 1H), 5.37 (d, J = 16.6Hz, 1H), 5.26 (dd, J = 1.0, 10.2Hz, 1H), 4.53 (m, 1H), 4.37 (dd, J = 7 5, 9.8Hz, 1H), 3.70 (dd, J = 3.7, 9 8Hz, 1H), 3.11 (m, 1H), 2.97 (dd, J = 6.1, 14.2Hz, 1H), 2 84 (dd , J = 9 5, 14.2Hz, 1H), 2.59 (m, 1H), 2 08-1.99 (m, 1H), 1.93 (s, 3H) (MH) - = 301, (M + H) * = 303 Example 128 Salt of acid hydrochloric acid (±) - (2R, 3S, 5R, 1'S) -2-M-acetamido-4-phenylbutyl-3-vinyl-pyrrolidine-5-carboxylic acid The organocuprate reagent was prepared from a reagent Grignard and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 123M, but using 1M phenethylmagnesium chloride instead of 1M ethylmagnesium bromide. 1H NMR (MeOD-d3) d 7.29-7.13 (m, 5H), 5.77-5.65 (m, 1H), 5.24 (d, J = 16.6Hz, 1H), 5.13 (dd, J = 1.0, 98Hz, 1H) , 4.33 (dd, J = 7.5, 10.2Hz, 1H), 4.22 (m, 1H), 3.62 (dd, J = 34, 9.8Hz, 1H), 2.98 (m, 1H), 2.63 (m, 2H), 2.54 (m, 1H), 2.06-1.95 (m, 1H), 2.03 (s, 3H), 1.79-1.55 (m, 4H) (MH) '= 329, (M + H) * = 331 Example 129 Salt of hydrochloric acid of (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-f eni Dbuyl-3-vi or l-pyrrolidine-5-carboxylic acid Organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) bromide / dimethyl sulfide complex, according to the methods described in Example 123M, but using 2M of benzylmagnesium chloride instead of 1M ethylmagnesium bromide: 1H NMR (MeOD-d3) d 7.30-7.17 (m, 5H), 5.82-5.70 (m, 1H), 5.28 (d, J = 17.0Hz, 1H), 5.17 (d, J = 11.2Hz, 1H), 4.33 (dd, J = 7.5, 10.2Hz, 1H), 4.18 (m, 1H), 3.64 (dd, J = 3.4, 9.8Hz, 1H), 3.01 (m, 1H), 2.78 ( m, 1H), 2.66-2.50 (m, 2H), 2.07 (s, 3H), 2.07-1.85 (m, 3H) (MH) = 315, (M + H) * = 317 EXAMPLE 130 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1 'S -2- (1-acetamido-2-propen-2-yl) ethyl-3-vinyl-pyrrolidin-5- carboxylic 130A t-butyl ester of acid (± - (2R, 3S.5R, 1 'S) -1-f-butoxycarbonyl-2- (N-f-butoxycarbonylaziridinyl) -3-vinyl-pyrrolidine-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2-aziridinyl-3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester (0.058 g, 0.17 mmol) was reacted with di-f-butyldicarbonate (95 mg, 0.44 mmol) and triethylamine (0.12 mL, 0.86 mmol) in dichloromethane (2.0 mL) at room temperature for 1 hour. The reaction was fired with saturated sodium bicarbonate (1.0 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate / dichloromethane 0-15% to give the title compound (yield: 0.060 g, 80%). 1H NMR (DMSO-de) (rotamers) d 5.97-5.78 (m, 1H), 5.06-4.93 (m, 2H), 4.15 (dd, J = 2.0, 9.8Hz, 1H), 3.40-3.28 (m, 1H ), 2.94-2.49 (m, 3H), 2.39 and 2.33 (2d, J = 6.1, 6.4Hz, 1H), 2.17 and 2.11 (2d, J = 3.7, 3.4, 1H), 1.81-1.69 (m, 1H) , 1.42-1 36 (m.27H) MS: (M + Na) * = 461 (weak). 130B (±) - (2R.3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-N-butoxycarbonylamino-2-propen-2-yl) ethyl-3 acid t-butyl ester -vinyl-pyrrolidone-5-carboxylic acid. To a suspension of copper bromide (l) / dimethyl sulfide complex (0.026 g, 0.127 mmol) in THF (1.0 ml) at 0 ° C was added isopropenylmagnesium bromide (0.5M) (1.0 ml, 0.50 mmol) in THF . After stirring for 10 minutes at 0 ° C, the mixture was cooled to -78 ° C and a solution of t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f was added dropwise. -butoxycarbonyl-2- (N-butoxycarbonylaziridinyl) -3-vinyl-pyrrolidine-5-carboxylic acid (0.030 g, 0.068 mmol) in THF (1.0 ml). After stirring for 10 minutes at -78 ° C, the reaction was warmed to 0 ° C and stirred for 2 hours. The reaction was set with saturated ammonium chloride (1.0 mL) and diluted with ethyl acetate (10 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate / dichloromethane 0-10% to give the title compound (yield: 0.026 g, 79%). 1 H NMR (DMSO-de) (rotamers) d 6.64 (m, 1H), 5.96-5.76 (m, 1H), 4.98-4.89 (m, 2H), 4.76-4.68 (m, 2H), 4.40-4.25 (m , 1H), 3.94 (m, 1H), 3.60-353 (m, 1H), 3.02-2.86 (m, 1H), 262-2.42 (m, 1H), 2.10-1 99 (m, 2H), 1.72 and 1.70 (2s, 3H), 1 72-1.55 (m, 1H), 1.44-1 34 (, 27H) MS: (M-H) - = 479, (M + H) * = 481 130C t-butyl ester of (±) - (2R.3S.5R.1'S) -1-f-butoxycarbonyl-2- (1-Nf-butoxycarbon mido-2-propen-2-yl) eti I -3 -vinyl-pyrrolidine-5-carboxylic acid. The t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-t-bu toxic rbonyl-2- (1-N-butoxycarb-onylamino-2-pro pen-2-yl) was reacted Ethyl-3-vinyl-pyrrolidine-5-carboxylic acid (0.024 g, 0.050 mmol) with lithium hexamethyldisilazide (1 M) (0.60 mL, 0.60 mmol) in THF (2.0 mL) at -25 ° C for 1 hour. To the preceding reaction, then acetyl chloride (0.085 mL, 1.20 mmol) was added at -25 ° C and the mixture was stirred for 30 minutes. The reaction was set with saturated sodium bicarbonate (2.0 mL) and stirred for 30 minutes at room temperature. The reaction was diluted with ethyl acetate (20 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using a gradient of 0-15% ethyl acetate / hexane to give the title compound (yield: 0.015 g, 58%) together with unreacted starting material. 1H NMR (DMSO-d6) (rotamers) d 601-5.84 (, 1H), 4.99-4.89 (m, 2H), 4.76-4.58 (m, 3H), 4.33 and 423 (2d, J = 7 8, 8 1Hz , 1H), 4.13- 404 (m, 1H), 269 (, 1H), 2.62-2.42 (m, 1H), 229 (br s, 3H), 2.35-2.14 (m, 2H), 1 76-1.55 (m, 1H), 1.60 (s, 3H), 1.50-1 35 (m, 27H) MS- (M + H) * = 523 130DSal of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2-propen-2-yl) ethyl -3-vinyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1, S) -1-f-butoxycarbonyl-2- (1) -substituted t-butyl ester. -N-butoxycarbonyl-acetamido-2-propen-2-yl) etl-3-vinyl-pyrrolidin-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid. (yield: 12 mg, 99%) 1H NMR (MeOD-d3) d 5.83-5.70 (m, 1H), 530 (dd, J = 0.7, 17. OHz, 1H), 5.19 (d, J = 10.2Hz, 1H), 4.79 (s, 1H), 471 (s, 1H), 4.46 (m, 1H), 4.30 (dd, J = 7.8, 9.8Hz, 1H), 3.66 (dd, J = 3.7, 98Hz, 1H) , 303 (m, 1H), 2.56 (m, 1H), 2.40-2.19 (m, 2H), 2.08-1.96 (m, 1H), 2.01 (s, 3H), 1.76 (s, 3H) (MH) " = 265, (M + H) * = 267 TO-- •-" Examples 131-135 BocHN The following title compounds were prepared in 4 steps according to the methods described in Example 130, substituting the reagents indicated for step 1 and their respective methods of preparation by isopropenyl cuprate and their preparation in 130B Example 131 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'S) -2- (1-acetamido-1- (c / syt ra ns) - pro pe n- 1 -i De t il- 3- VI NON-RETROID-5-CARBOXYLLICINE The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 130B, but using 0.5M of 1-propenylmagnesium bromide (mixture of cis and trans isomers) instead of 0.5M of isopropenylmagnesium bromide 1 H NMR (MeOD-d 3) (2: 1 trans: cis ratio) d 5.81-5.54 (m, 2H), 5.43-530 (m, 1H), 5.33-5.27 (m, 0.33H, cis isomer), 5.31- 5.25 (m, 0.66H, trans isomer), 520-5.15 (m, 1H), 426-4 17 (, 2H), 3.65 (dd, J = 3.4, 9.8Hz, 1H), 2.98 (m, 1H), 2.58-2.48 (m, 1H), 2.45-2.19 (m, 2H), 2.08-1.94 (m, 1H), 2.02 (s, 3H), 1.68 (m, 2H, trans isomer), 1.63 (m, 1H, cis isomer) (MH) = 265, (M + H) * = 267 Example 132 Salt of trifluoroacetic acid acid (±) - (2R, 3S.5R.1 'S) -2- (1-acetamido-2-allyl) methyl-3-vinyl-pyrrolidine-5-carboxylic acid The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 130B, but using 1M of vinylmagnesium bromide in 0.5M bromide isopropenylmagnesium 1H NMR (MeOD-d3) d 5.83-5.70 (m, 2H), 5.28 (d, J = 17.0Hz, 1H), 5.19-5.13 (m, 3H), 4.28 (, 1H), 4.19 (dd, J = 8.5, 9.1Hz, 1H), 3.66 (dd, J = 3.4, 9.5Hz, 1H), 2.99 (m, 1H), 257-2.48 (m, 1H), 2.44-2.26 (m, 2H), 2.05-1.93 (m, 1H), 2.01 (s, 3H) (M + H) * = 253 Example 133 Salt of trifluoroacetic acid acid (±) - (2R.3S, 5R, 1'S) -2- (1-acetamido) -2- (1-buten-2-yl) ethyl-3-vinyl-pyrroli in-5- carboxyl? co The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) / dimethyl sulfide complex, according to the methods described in Example 130B, but using 0.5M bromide of 1-buten-2-ylmagnesium instead of 0.5M of isopropenylmagnesium bromide. 1 H NMR (MeOD-d 3) d 5.81-5.73 (m, 1 H), 5.30 (d, J = 17.1 Hz, 1 H), 5.19 (d, J = 10 OHz, 1 H), 4.93 (s, 1 H), 4.83 ( s, 1H), 4.45 (m, 1H), 4.31 (dd, J = 7.6, 9.8Hz, 1H), 3.69 (dd, J = 32, 9.8Hz, 1H), 3.03 (m, 1H), 2.59-2.53 (m, 1H), 2.38 (dd, J = 5.9, 14.9Hz, 1H), 2.30 (dd, J = 9.5, 14.9Hz, 1H), 2.07 (q, J = 7.6Hz, 2H), 2.05-1.99 ( m, 1H), 2.01 (s, 3H), 1.05 (t, J = 7.6Hz, 3H) (M + H) * = 281 Example 134 Salt of trifluoroacetic acid acid (±) - (2R.3S.5R.1'S) -2- (1-acet amido-2- (frans-2-bu te n-2-ypethyl-3-vinyl-pyrrolidin-5) -lolly box The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) bromide / dimethyl sulfide complex, according to the methods described in Example 130B, but using 0.5M of 1- bromide methyl-1-propenylmagnesium instead of 0.5M isopropenylmagnesium bromide. H NMR (MeOD-d3) d 5.83-5.71 (m, 1H), 5.41 (q, J = 6.8Hz, 1H), 5.31 (d, J = 17.3Hz, 1H), 5.19 (d, J = 10.2Hz, 1H), 4.42 (m, 1H), 4.31 (dd, J = 7.5, 9.8Hz, 1H), 3.61 (dd, J = 4.0, 9.8Hz, 1H), 3.01 (, 1H), 2.62-2.52 (m, 1H), 2.46 (dd, J = 9.5, 13.9Hz, 1H), 2.26 (dd, J = 5.8, 13.9Hz, 1H), 2.09-1.99 (m, 1H), 2.00 (s, 3H), 1.72 (s) , 3H), 1.59 (d, J = 6.8Hz, 3H) (M + H) * = 281 Example 135 Salt of the acid trifluoroacetic acid (±) - (2R.3S.5R, 1'S.3'RS) -2- (1-acetamido-3-methyl-yl) pentyl-3-vinyl-pyrrole? D? N-5- carboxylic The organocuprate reagent was prepared from a Grignard reagent and a catalytic amount of the copper (l) bromide / dimethyl sulfide complex, according to the methods described in Example 130B, but using 2M sec-butylmagnesium in place 0.5M of 1-NMR sopropenylmagnesium bromide (MeOD-d3) (1.1 mixture of methyl isomers) d 582-5.69 (, 1H), 5.27 (d, J = 17.0Hz, 0.5H), 5.25 (d, J = 17.0Hz, 0.5H), 5.15 (d, J = 10.2Hz, 1H), 4.33 (m, 1H), 4.18 (dd, J = 2.7, 7.5Hz, 0.5H), 4.15 (dd, J = 3.0 , 7.8Hz, 0.5H), 3.62 (dd, J = 3.1 9.8Hz, 05H), 3.57 (dd, J = 4.07, 9.8Hz, 0.5H), 2.97 (m, 1H), 2.57-247 (m, 1H ), 2.03-1.92 (m, 1H), 2.03 (s, 1.5H), 2.02 (s, 1.5H), 1.72-1 06 (m, 5H), 0.95-0.86 (m, 6H) (M + H) * = 283 EXAMPLE 136 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'RS) -2- (1-acetamido-1- (N-methyl-N-benzylcarbamoyl) methyl-3-vinyl-pyrrolidyl) n-5-carboxylic 136A (±) - (2R, 3S, 5R, 1 'R) -1-f-butoxycarbonyl-2- (1-acetamido-1-carboxy) methyl-3-vinyl-pyrrolidinyl- t-butyl ester 5-carboxylic acid The title compound was prepared according to the method of Example 2B using t-butyl ester of the (±) - (2R, 3S, 5R, 1'R) -1-f- bu toxic rbonyl-2- (1-ace-tamido-1-formyl) -methyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) -1-benzyl- t-butyl ester 2- (1-Acetamido-3-ethyl) pentyl-3-formyl-pyrrolidine-5-carboxylic acid. 136B (±) - (2R.3S, 5R, 1'RS) -1-f-butoxycarbonyl-2- (1-acetamido-2- (N-methyl-N-benzylcarbamoyl) methyl-3 acid t-butyl ester -vinyl-? -rolididin-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R) -1-t-butoxycarbonyl-2- (1-acetamido-1-) t-butyl ester was reacted carboxyl) methyl-3-vinyl-pyrrolidine-5-carboxylic acid (36 mg, 0.09 mmol) with N-methyl-N-benzylamine (32 mg, 0 26 mmol), dimethylaminopyridine (1 mg, 0.008 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (30 mg, 0.16 mmol) in DMF (3 mL) at 25 ° C for 16 hours. The reaction was set with water (3 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 50% ethyl acetate / hexane to give the title compound. MS: (M + H) * = 516, (M-H) - = 514 136C Salt of trifluoroacetic acid of (±) - (2R.3S, 5R.1 RS) -2- (1-acetamido-1- (N-methyl-N-benzylcarbamoyl) methyl-3-vinyl-pyrrolidin-5- carboxylic The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'RS) -1-f-butoxycarbonyl-2-t-butyl ester. - (1-Acetamido-2- (N-methyl-N-benzylcarbamoyl) methyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3S, 5R, 1 ') t-butyl ester R, 2, S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield : 7 mg, 95%) .1H NMR (DMSO-de) d 8.52 (d.J = 9.7HZ, 1H), 7.30 (, 5H), 5.65 (m, 1H), 5.12 (m, 4H), 4.62 (m, 1H), 4.40 (m, 2H), 3.70 (m, 1H), 2.90 (s, 3H), 2.20 (m, 2H), 1.96 (s, 3H) ), MS: (M + H) * = 360, (M + 23) * = 382 Example 138 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R) -2- (1- to ce-2-tamido (N-phenyl-carbonyloxy) e ti l-3 vinyl-pyrrolidine-5-carboxylic acid 138A (+) - (2R.3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-aceta-ido-2-N-phenyl-carbonyloxy) ethyl ester t-butyl ester 3-vinyl-pyrrolidine-5-carboxylic acid The (±) - (2R, 3S, 5R, 1'R) -1- f -butoxycarbonyl-2- (1 -acetam id or-2-hydroxy) eti I-3 was reacted with t-butyl ester. - i or I-pirro I idi n-5-carboxylic acid (18 mg, 0.045 mmol) with phenylisocyanate (16 mg, 0.14 mmol) and pyridine (0.1 ml) in THF (3 L) at 25 ° C for 16 hours. The reaction was set with water (2 L) and diluted with ethyl acetate (10 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using ethyl acetate / hexane at 50% to give the title compound (yield: 7.5 mg, 33%). MS: (M + H) * = 518, (M-H) '= 516 138Sulfuric acid acetic acid (±) - (2R.3S, 5R.1'R) -2- (1-acetamido-1- (N-phenylcarbonyloxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (+) - (2 R, 3S, 5R, 1 'R) -1-f-butoxycarbonyl- t-butyl ester. 2- (1 -acetam-ido-2-Nf in I-carbonyloxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1 ') t-butyl ester R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) but i-3- (cs-pro? En-1-yl) -? -rolyolidin-5-ca carboxylic acid (yield: 4 mg, 95%). H NMR (DMSO-de) d 8.36 (d, J = 9.7HZ, 1H), 7.30 (m, 5H), 5.78 (m, 1H), 5.22 (m, 1H), 5.10 (m, 1H), 4.58 ( m, 1H), 4.45 (m, 1H), 4.14 (, 2H), 3.58 (m, 1H), 2.88 (m, 1H), 2.27 (m, 1H), 2.12 (m, 1H), 1.88 (s, 3H) MS: (M + H) * = 362, (M + 23) * = 384, (MH) "= 360, (M + 35)" = 396 EXAMPLE 139 Salt of trifluoroacetic acid of (+ 1-Í2R.3S.5R.1 'R) -2- (1-acetamido-1-isobutyryloxy) etl-3-vinyl-pyrrolidine-5-carboxylic acid 139A (±) - (2R.3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1 -acetam ido-2-isobutyryloxy) ethyl-3-vi or l-pyrrolidine acid t-butyl ester -5-carboxyl ico The (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) t-butyl ester was reacted. ) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid (15 mg, 0.04 mmol) with isobutyryl chloride (8 mg, 0.08 mmol) and triethylamine (8 mg, 0.08 mmol) in dichloromethane (4 mL) at 0o C for 2 hours. The reaction was set with water (3 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 30% ethyl acetate / hexane to give the title compound (yield: 11 mg, 63%). MS: (M + H) * = 469, (M-H) - = 467 139B Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1 'R) -2- (1-acetamido-1-isobutyryloxy?) And il-3-vi or l-pyrrolidine-5-carboxyl ico The title compound was prepared according to the method 5 described in Example 41C, using (+) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl t-butyl ester -2- (1 -acetamido-2-isobutyroxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-f-butox? Carbon? L-2- (1-acetamido-2-hydroxy!) Butyl-3- (c; 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 6.0 mg, 96%). H NMR (DMSO-dβ) 5 8.00 (d, J = 9.9HZ, 1H), 5.63 (m, 1H), 5.08 (m, 1H), 4.98 (m, 1H), 4.35 (m, 1H), 425 ( m, 1H), 408 (m, 1H), 3.55 (m, 1H), 3.45 (m, 1H), 3.38 (m, 1H), 2.83 (m, 1H), 2.33 (m, 1H), 1.78 (s) , 3H) MS- (M + H) * = 243, (M + 23) * = 265, (MH) - = 241 15 twenty EXAMPLE 140 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R) -2- (1-acetamido-2-N-ethyl-t-orcarbonyloxy) -ethyl-3-vin? l-pyrrole? din-5-carboxyl? co 140A (±) - (2R, 3S.5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-N-ethyl-thiocarbonyloxy) ethyl-3-butyl ester vin i I-pyrro lidin-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R) -1-f-butoxy carbon il-2- (1-acetamide) -2-h id roxi) ethyl-3-v ini l-pyrrolidine-5-carboxylic acid (17 mg, 0.04 mmol) with ethylisothiocyanate (19 mg, 0.21 mmol) in pyridine (2 mL) at 70 ° C for 17 hours . The reaction was set with water (3 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 70% ethyl acetate / hexane to give the title compound (yield: 10 mg, 48%). MS: (M + H) * = 486, (M + 23) * = 508, (M-H) '= 485 140B Salt of the trifluoroacetic acid of (+) - (2R, 3S, 5R, 1'R) -2- (1-acetamido-2-N-ethyl-thiocarbonyloxy) ethyl-3-vinyl-pyrrolidin-5- carboxylic The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2-t-butyl ester. - (1-Acetamido-2-N-ethyl-thiocarbonyloxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester ) -1-f-butoxycarbonyl-2- (1-aceta-ido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 7 mg, 94% ). 1 H NMR (DMSO-dβ) 68.30 (d, J = 9.7HZ, 1H), 5.78 (m, 1H), 5.25 (m, 1H), 5.12 (m, 1H), 4.50 (m, 1H), 4.33 (m , 1H), 4.18 (m, 2H), 3.72 (m, 1H), 3.55 (m, 2H), 2.30 (m, 1H), 2.10 (m, 1H), 1.82 (s, 3H), 1.17 (m, 3H) MS: (M + H) * = 330, (MH) - = 328 Example 141 (±) - (2R, 3S.5R.1'S) -2- (1-Acetamido-2-amino) etl 3-vinyl-? -rolidolidin-5-carboxylic acid hydrochloride 141A (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-aceta-ido-2-f-butoxycarbonylamino) ethyl-3-vinyl-pyrrolidin-5-butyl ester -carboxylic The (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-azido) ethyl-3-vinyl-pyrrolidin-5-butyl ester was reacted carboxylic acid (9.5 mg, 0.022 mmol) with triphenylphosphine (23.5 mg, 0.090 mmol) in ethanol (180 μL) and water (45 μL) at 70 ° C for 30 minutes. The reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (220 μL) and di-ferf-butyl dicarbonate (7.3 mg, 0.034 mmol) and N, N-diisopropylethylamine (11.7 L, 0.067 mmol) were added at 25 ° C. After 1 hour the mixture of reaction was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO 4 and concentrated in vacuo. The residue was purified by chromatography on silica gel using 100% dichloromethane relative to dichloromethane / 50% ethyl acetate to give the title compound (yield: 7.5 mg, 67%). 1H NMR (DMSO-de) (rotamers) d 7.51 (d, J = 10.5Hz, 1H), 6.80- 6. 66 (m, 1H), 5.90-5.76 (m, 1H), 5.02-4.90 (m, 2H), 4.38-4.19 (m, 1H), 3.98-3.94 (m, 1H), 3.68-3.62 (m, 1H) ), 3.09-2.73 (m, 2H), 2.60-2.42 (m, 1H), 1.80 (s, 3H), 1.72-1.62 (m, 1H), 1.42-1.34 (m, 27H). MS: (M + H) * = 498, (M + Na) * = 520, (M-H) "= 496, (M + CI)" = 532 141B (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2-amino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared in accordance with method as described in Example 1K, using (±) - (2, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-f-butoxy-carbonylamino) t-butyl ester ) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (±) (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl t-butyl ester -pyrrolidine-5-carboxylic acid (yield: 3.65 mg, 99%). 1H NMR (DMSO-dβ) d 8.24 (d, J = 7.9Hz, 1H), 5.75-5.68 (m, 1H), 5.16 (d, J = 17.1Hz, 1H), 5.06 (d, J = 10.4Hz, 1H), 4.37-4.27 (m, 2H), 3.60-3.16 (m, 2H), 3.00-2.88 (m, 2H), 2.46-2.36 (m, 1H), 1.91-1.81 (m, 1H), 1.86 ( s, 3H). MS: (M + H) * = 242, (M + Na) * = 264, (M-H) '= 240, (2M-H)' = 481 Example 142 (±) - (2R, 3S.5R, 1 'S) -2- (1-acetamido-2-acetamido) -ethyl-3-vinyl-pyrrole-din-5-carboxylic acid hydrochloride 142A (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-acetamido) ethyl-3-vinyl-pyrrolidone t-butyl ester 5-carboxy I ico. The (±) - (2R, 3S, 5R, 1'S) -1-f-butoxicand rbonyl-2- (1 -aceta-my-do-2-amino) -ethyl-3-vinyl acid t-butyl ester was reacted -pyrrole di n-5-carboxylic acid (9.4 mg, 0.024 mmol) with acetic anhydride (11.2 μL) and triethylamine (33.1 μL) in dichloromethane (0.23 L) at 0 ° C for 1 hour. The reaction was diluted with water (3 mL), extracted with ethyl acetate (12 mL), washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography on silica gel using 100% ethyl acetate with respect to ethyl acetate / 90% methanol to give the title compound (yield: 6.8mg, 66%). 1 H NMR (DMSO-de) (rotamers) 7.79-7.74 (m, 1H), 7.54 (d, J = 9.8Hz, 1H), 5.97-5.81 (m, 1H), 5.01-4.91 (m, 2H), 4.36-4.27 (m, 1H), 3.97-3.90 (m, 1H), 3.68-3.63 (m, 1H), 3.21-3.15 (m, 1H), 3.10-2.76 (m, 1H), 2.88-2.78 (m , 1H), 2.58-2.45 (m, 1H), 1.81 (s, 3H), 1.78 (s, 3H), 1.76-1.64 (m, 1H), 1.42-1.36 (m, 18H). MS: (M + H) * = 439, (M + Na) * = 462, (M-H) '= 438, (M + 35) = 474 142B Acid chlorhydrate (±) - (2R.3S.5R, 1 'S) -2- (1-Acetamido-2-acetamido) et? L-3-vinyl-pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 1K, using t-butyl ester of the acid salt (±) - (2R, 3S, 5R, 1'S) -2- (1, 2-d? -acetamido) ) butyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) (2 R, 3R, 5 R, 1'S) -2- (1 -acetamido-3-ethyl) pen -3- methoxymethyl-pyrrolidine-5-carboxylic acid (yield.3.30 mg, 80%). MS: (M + H) * = 284, (M-H) '= 282, (M + CI)' = 318 Example 143 (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2-azido) et? -1-3-vinyl-p? Rrolidine-5-carboxylic acid hydrochloride 143A (±) - (2R, 3S, 5R, 1'S) -1-t-butoxycarbonyl-2- (1-N-acetamido-2-azido) -ethyl-3-vinyl-pyrrolidine- t-butyl ester 5-carboxylic. (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (N-acetylaziridinyl) -3-vinyl-pyrrolidone-5-butyl ester was reacted -carboxylic (21.6 mg, 0064 mmol) with sodium azide (41 6 mg, 0.64 mmol) and Ammonium chloride (34.2 mg, 064 mmol) in ethanol (270 μL) and water (30 μL) at 75 ° C for 1 hour. The ethanol was then removed in vacuo and the remaining aqueous was extracted with ethyl acetate. The combined organics were washed with brine, dried over MgSO4 and concentrated in vacuo (crude yield, 20mg, 82%). To the crude mixture was added acetic anhydride (31 μL, 0.33 mmol) and triethylamine (92 μL, 0.66 mmol) in dichloromethane (330 μL) at 0 ° C for 30 minutes. The reaction mixture was then concentrated in vacuo. The residue was purified by chromatography on silica gel using 100% dichloromethane relative to dichloromethane / 50% ethyl acetate to give the title compound (yield: 10 mg, 60%). 1H NMR (DMSO-d6) (rotamers) 5 7.85 and 7.81 (d, J = 9.5Hz and 9.8Hz, 1H), 5.94-5.80 (m, 1H), 5.04-4.93 (m, 2H), 4.58-4.38 ( m, 1H), 4.04-3.96 (m, 1H), 3.72-3.66 (m, 1H), 3.41-3.21 (m, 2H), 3.09-2.79 (m, 1H), 2.59-2.46 (m, 1H), 1.84-1.82 (m, 3H), 1.79-1.53 (m, 1H), 1 43-1.35 (m, 18H). MS: (M + H) * = 424, (M + Na) * = 446, (2M + Na) * = 869, (M-H) '= 422, (M + CI) "= 458. 143B (+) - (2R.3S.5R.1 'S) -2- (1-acetamido-2-azido) ethyl-3-v? Nyl-pyrrolidine-5-carboxylic acid hydrochloride salt The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-) t-butyl ester. acetamido-2-azido) ethyl-3-v? nyl-pyrrolid? n-5-carboxylic acid instead of t-butyl ester of (±) (2R, 3R, 5, 1'S) -2- (1-acetamido- 3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 2.94 mg, 93%). 1H NMR (DMSO-de) d 8.24 (d, J = 855Hz, 1H), 5.74-5.67 (m, 1H), 5.14 (d, J = 17.1Hz, 1H), 5.06 (d, J = 104Hz, 1H) , 4.41-4.35 (m, 2H), 3.57-3.36 (m, 3H), 2.93-2.90 (m, 1H), 2.44-238 (m, 1H), 1.96-1.84 (m, 1H), 1.84 (s, 3H). MS: (M + H) * = 268, (M-H) = 266, (M + CI) - = 302 Example 144 (±) - (2R.3S.5R.1 'S) -2- (1-Acetamido-2-N-methylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride 144A (+) - (2R.3S.5R, 1'S) -1- f -butoxycarbonyl-2- (1-N-acetamido-2-N-ritylamino) -thyl-3-vinyl-pyrrolidin- tert-butyl ester 5-carboxylic acid Methylamine (.016 g, .53 mmol) was reacted with N.O-bis-tri-ethylsilylacetamide (0.09 g, 0.39 mmol) in DMSO (0.8 mL) at 0 ° C for 1 hour. The (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (N-acetylazipdinyl) -3-vinyl-pyrrolidine-5-carboxylic acid t-butyl ester (.040) was then reacted. g, .11 mmol) with N-trimethyl-silylmethylamine from the preceding reagent at 75 ° C for 18 hours. The reaction was diluted with ethyl acetate (7 mL), washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using chloroform-methanol-ammonia to give the title compound (yield: 0.011 g, 25%). 1H NMR (CDCU) 5 5.78-5.98 (m, 1H), 5.90-5.04 (2m, 2H), 4.40-4.55 (brm, 1H), 3.90-4.02 (, 1H), 3.64-3.75 (2m, 1H), 2.25-2.40 (brm 3H), 2.83.2.85 (2d, 3H), 1.42.1.44 (2s, 9H), 1.34.1.37 (2s, 9H). MS: (M + H) * = 412 144B Acid salt dihydrochloride (±) - (2R.3S.5R.1 'S) -2-f1-acetamido-2-N-methylamino) et? L-3-vinyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 1K, using (±) - (2 R, 3S, 5R, 1'S) -1-f-bu toxy carbonyl l-2-t-butyl ester - (1 -acetamido-2-N-methylamino) ethyl-3-vinyl-pyrrolidine-5-carboxyl? Co in place of (±) (2 R, 3 R, 5 R, 1'S) t-butyl ester) -2- (1-Acetam-ido-3-ethyl) penyl-3-methoxy-methyl-1-pyrrolidine-5-carboxylic acid (Yield: 7.2 mg, 99%). 1 H NMR (DMSO-de) d 8.25 (d, 1H), 570 (m, 1H), 5.10 (m, 2H), 4.50 (m, 1H), 4.40 (m, 1H), 2.55 (s, 3H), 1.85 (s, 3H). MS: (M + H) * = 256.

Examples 145-164 AcN H N Dßoyc The following title compounds were prepared according to the methods described in Examples 141-144, wherein R 'is Gual to hydrogen. Where R or R 'are not equal to hydrogen, the corresponding amine was used directly without the intervention of trimethylsilylation. * ltfí Example 145 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2-Ni so prop i lami) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-de) d 8.30 (d, 1H), 5.70 (m, 1H), 5.10 (m, 2H), 4.40 (br, 2H), 3.52-3.68 (br, 1H), 3.10-3.20 (br , 1H), 2.82-2.97 (br, 1H), 2.37-2.47 (br, 1H), 1.88 (s, 3H), 1.25 (d, 6H). MS: (M + H) * = 284 Example 146 (±) - (2R, 3S, 5R, 1'S) -2-M-Acetamido-2-N-butylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid dihydrochloride 1H NMR (DMSO-de) 5 8.25 (d, 1H), 5.70 (m, 1H), 5.10 (m, 2H), 4.50 (m, 1H), 4.38 (m, 1H), 3.60 (m, 1H), 2.90 (m, 3H), 2.40 (m, 2H), 1.87 (s, 3H), 1.62 (m, 2H), 1.33 (m, 2H), 0.90 (t, 3H). MS: (M + H) * = 298 Example 147 Acid hydrochloride (±) - (2R.3S, 5R, 1'S) -2- (1-Acetamido-2-N-benzylamino) ethyl-3-vinyl-pyrrolidin-5-carboxylic acid 1H NMR (DMSO-de) 7.56-7.43 (m, 5H), 5.74-5.67 (m, 1H), 5.15-4.99 (m, 2H), 4.56 (m, 1H), 4.27-3.93 (m, 3H), 3.66-3.15 (m, 3H) ), 2.91-2.88 (m, 1H), 2.64-2.34 (m, 2H), 1.86 (s, 3H). MS: (M + H) * = 332, (M + Na) * = 354, (M-H) = 330, (2M-H) = 661 Example 148 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2-N-phenethylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-de) d 8.25 (d, 1H), 7.30 (m, 5H), 5.70 (m, 1H), 5.10 (m, 2H), 4.50 (br, 1H), 4.35 (br, 1H), 3.61 (m, 1H), 3.17 (m, 3H), 2.98 (m, 3H), 2.42 (m, 1H), 1.88 (s, 3H). MS: (M + H) * = 346 Example 149 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2-NN-d-methylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-dβ) d 8.34 (d, J = 9.2Hz, 1H), 5.74-5.67 (m, 1H), 5.12 (d, J = 17.1Hz, 1H), 5.04 (d, J = 10.4Hz, 1H) , 4.67-4.62 (m, 1H), 4.40 (dd, J = 7.3, 10.4Hz, 1H), 3.60-3.11 (m, 3H), 2.96-2.83 (m, 1H), 2.50 (s, 6H), 2.44 -2.38 (m, 1H), 1.92-1.84 (m, 1H), 1.84 (s, 3H). MS: (M + H) * = 270, (M + Na) * = 292, (M-H) - = 268.

Example 150 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2-NN-diethylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic H NMR (DMSO-de) d 8.23 (d.1H), 5.70 (m, 1H), 5.10 (m, 2H), 4.60 (br, 1H), 4.40 (br, 1H), 3.12 (m, 4H), 2.88 (m, 1H), 2.42 (m, 1H), 1.85 (s, 3H), 1.22 (t, 3H). MS- (M + H) * = 298 Example 151 Acid dihydrochloride (±) - (2R.3S.5R, 1'S) -2- (1-Acetamido-2-NN-dibutylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-de) d 8.24 (d, 1H), 5.70 (m, 1H), 5.08 (m, 2H), 4.48-4.62 (br, 1H), 4.28-4.43 (1H), 3.05 (m, 4H), 2.77-2.92 (br, 1H), 2.34-2.46 (br, 2H), 1.84 (s, 3H), 1.64 (m, 4H), 1.30 (m, 4H), 0.93 (t, 6H). MS: (M + H) * = 354 Example 152 Acid dihydrochloride (±) - (2R.3S.5R.1 'S) -2- (1-Acetamido-2- (N-2-hydroxyethylamino)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-de) d 8.20 (d, 1H), 5.70 (m, 1H), 5.15 (d, 1H), 5.08 (d, 1H), 4.50 (brm, 1H), 4.38 (brm, 1H), 3.68 (M, 1H), 3.0 (brm, 2H), 2. 90 (m, 1H), 2.41 (m, 1H), 1 85 (s, 3H). MS- (M + H) * = 286 Example 153 Acid dihydrochloride (±) -f2R.3S.5R.1, S) -2- (1-Acetamido-2- (N-2-hydroxyethyl-N-ethylamino)) ethyl-3-vinyl-pyrrolidin-5- 1H NMR carboxylic acid (DMSO-de) d 5.81-5.74 (m, 1H), 5.38 (d, J = 17.1Hz, 1H), 5.22 (d, J = 10.0Hz, 1H), 4.92-4.88 (m, 1H) , 4.48 (dd, J = 7.6, 9.8Hz, 1H), 3.91 (t, J = 4.9Hz, 2H), 3.85 (dd, J = 5.6, 10.0Hz, 1H), 3.63-3.53 (m, 2H), 3.46-3.39 (m, 4H), 3.16-3.13 (m, 1H), 2.66-2.61 (m, 1H), 2.08 (s, 3H), 2.06-2.01 (m, 1H), 1.38 (t, J = 7.33 , 3H). MS: (M + H) * = 314, (M + Na) * = 336, (M-H) - = 312, (M + CI) - = 348, (2M-H) - = 625 Example 154 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (N-2-hydroxyethyl-N-propylamino)) and thi-3-vinyl-pyrrolidin-5 - carboxylic H NMR (DMSO-d6) 58.36 (d, J = 8.5Hz. 1H), 5.75-5.68 (m, 1H), 5.13 (d, J = 17.1Hz, 1H), 5.04 (d, J = 10.4Hz , 1H), 4.62 (m, 1H), 4.36 (m, 1H), 3. 77 (t, J = 4.9Hz, 2H), 3.63-359 (m, 1H), 350-3.23 (m, 3H), 3.22-3.19 (m, 2H), 3.08 (t, J = 7.3Hz, 2H) , 2.91-2.87 (m, 1H), 2.44-2.39 (m, 1H), 1.99-1.88 (m, 1H), 1.84 (s, 3H), 1.75-1.70 (m, 2H), 0.90 (t, J = 6.7Hz, 3H). MS: (M + H) * = 328, (M + Na) * = 350, (M-H) - = 326, (M + CI) '= 362, (2M-H) - = 653 Example 155 Acid dihydrochloride (±) - (2R, 3S.5R, 1'S) -2- (1-Acetamido-2- (imidazol-1-yl)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (MeOD -d3) d9.06 (s, 1H), 7.72 (s, 1H), 7.58 (s, 1H), 5.84-5.76 (m, 1H), 5.39 (d, J = 17.1Hz, 1H), 5.23 (d , J = 10.25Hz, 1H), 4.70-4.66 (m, 1H), 4.52-4.43 (m, 2H), 3.92-3.89 (m, 1H), 3.20-3.17 (m, 1H), 2.67-2.62 (m , 1H), 2.11-2.04 (m, 1H), 1.95-1.89 (m, 1H), 1.91 (s, 3H). MS: (M + H) * = 293, (M-H) - = 291, (M + 35) * = 327.

Example 156 Acid dihydrochloride (±) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2- (N, N-di- (2-hydroxyethylamino)) ethyl-3-vinyl-pyrrolidin-5- carboxylic MS: (M + H) * = 330, (M + Na) * = 352, (MH) = 328, (M + CI) = 364 Example 157 Acid hydrochloride salt (±) - (2R.3S, 5R, 1'S) -2- (1-Acetamido-2- (N-acetyl-N-methylamino) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR ( DMSO-de) d 8.01.7.95 (2d, 1H), 5.68-5.80 (m, 1H), 5.02-5.22 (m, 2H), 4.30-4.45 (brm, 2H), 3.26.3.21 (2d, 1H), 2.82-2.95 (brm, 1H), 2.38-2.48 (m, 1H), 1.98.2.02 (2s, 3H), 1.79.1.82 (2s, 3H) MS: (M + H) * = 298 Example 158 Acid dihydrochloride (±) - (2R, 3S.5R, 1 'S) -2- (1-Acetamido-2- (N-2-hydroxyethyl-N-methylamino)) ethyl-3-vinyl-pyrrolidine -5-carboxylic acid 'H NMR (DMSO-de) 5 8.35 (d, J = 9.15Hz, 1H), 5.74-5.67 (m, 1H), 5.12 (d, J = 17.1Hz, 1H), 5.04 (d, J = 10.4Hz, 1H), 4.70 (m, 1H), 4.39 (dd, J = 7.3, 10.4Hz, 1H), 3.80-3.75 (m, 3H), 3.61-3.43 (m, 3H), 3.23-3.16 (m, 2H), 2.91-2.82 (m, 1H), 2.82 (s, 3H), 2.44-2.39 (m, 1H), 1.92-1.84 (m, 1H), 1.84 (s, 3H). MS: (M + H) * = 300, (M + Na) * = 322, (2M + H-H20) * = 581 Example 159 Acid dihydrochloride (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (N-propyl-N-methylamino) ethyl-3-vini I- pyrro lidin-5-carboxylic acid? NMR (DMSO-de) (broad) 5 8.3 (1H), 5.7 (1H), 5.12-5.04 (2H), 4.6 (1H), 4.35 (1H), 2.61-2.35 (11H), 1.9 (3H), 1 78-1.63 (2H), 1.9 (3H) MS: (M + H) * = 298, (M + Na) * = 320, (MH) = 296, (M + CI) '332, (2M- H) - = 593 Example 160 Acid hydrochloride salt (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (N-cyclo or hexyl-N-methylamino)) ethyl-3-vi or l-pyrrolidin-5 -carboxylic 1H NMR (DMSO-de) d 8.26 (m, 1H), 5.75-5.65 (m, 1H), 5.08 (d, J = 17.1Hz, 1H), 5.02 (d, J = 10.3Hz, 1H) , 4.62 (m, 1H), 4.43-4.40 (m, 1H), 3.62-3.58 (m, 1H), 3.46-3.16 (m, 2H), 2.89-2.84 (m, 1H), 2.72 (s, 3H) , 2.44-2.39 (m, 1H), 2.07-1.80 (m, 5H), 1.81 (s, 3H), 1.63 (m, 1H), 1.45-1.06 (m, 6H). MS: (M + H) * = 338, (M + Na) * = 360, (M-H) = 336, (M + CI) = 372 Example 161 I-acid dihydrochloride - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (N-benzyl-N-methylamino)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-d6) d 8.36 (m, 1H), 7.61-7.46 (m, 5H), 5.69-5.64 (m, 1H), 5.07 (d, J = 17.1Hz, 1H), 4.99 (d, J = 10 1Hz, 1H), 4.77 (m, 1H), 4. 44-439 (m, 2H), 425 (d, J = 12.9, 1H), 3.61 (m, 1H), 3.43 (m, 1H), 3.22 (m, 1H), 2.93-2.85 (m, 1H), 2.73 (s, 3H), 2.44-2.38 (m, 1H), 1.92-1.85 (m, 1H), 1.85 (s, 3H). MS. (M + H) * = 346 Example 162 Acid dihydrochloride (±) - (2R.3S.5R, 1'S) -2- (1-Acetamido-2- (N-phenethyl-N-methylamino)) et? L-3-vinyl-pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-de) 5 8.34 (d, J = 8.55Hz, 1H), 7.37-7.26 (m, 5H), 5.76-5.69 (m, 1H), 5.14 (d, J = 17.1Hz, 1H), 5.06 (d, J = 10.4Hz, 1H), 4.72 (m, 1H), 4.46-4.42 (m, 1H), 3.83-3.20 (m, 6H), 3.13-2.99 (m, 2H), 2.86 (s, 3H), 2.95-2.83 (m, 1H), 246-2.40 (m, 1H), 1.95-1.81 (m, 1H), 1.86 (s, 3H). MS: (M + H) * = 360 Example 163 (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2- (N-naphthylmethyl-N-methylamino)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid dihydrochloride 1H NMR (DMSO-dβ) d 8.41 (d, J = 7.3Hz, 1H), 8.32-7.59 (m, 7H), 5.60 (m, 1H), 5.04 (d, J = 17.1Hz, 1H), 4.91 ( d, J = 9.8Hz, 1H), 4.97-4.73 (m, 3H), 4.39 (m, 1H), 3.70-3.13 (m, 3H), 2.90 (m, 1H), 2.72 (s, 3H), 2.43 -2.41 (m, 1H), 2.01-1.74 (m, 1H), 1.87 (s, 3H). MS: (M + H) * = 395, (M + Na) * = 418, (M-H) - = 394, (M + CI) "= 430, (2M-H) '= 789 Example 164 Acid dihydrochloride (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2- (N-morpholinyl)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (DMSO-de ) d 8.28 (d, 1H), 575-5.78 (m, 1H), 5.15 (d, 1H), . 05 (d, 1H), 4.65 (brm, 1H), 4.42 (m, 1H), 3.72-3.98 (brm, 3H), 3.62 (, 1H), 2.90 (m, 1H), 2.38-2.48 (m, 1H), 1.85 (s, 3H). MS: (M + H) * = 312 EXAMPLE 165 (±) - (2R, 3S, 5R, 1'S, 3'R) -2- (1-Acetamido-2- (N-methyl-N-butylamino-N-oxide)) ethyl-3 hydrochloride salt -vinyl-pyrrolidine-5-carboxylic acid 165A (±) - (2R.3S.5R.1'S, 3'R) t-butyl ester and (±) - (2R, 3S, 5R. 1'S.3'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2- (N-methyl-N-t-butylamino-N-oxide)) ethyl-pyrrolidine-5-carboxylic acid. Reacted t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f- Butoxycarbonyl-2- (1-acetamido-2- (N-methyl-Nt-buty lami)) ) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid (37 mg, 0.08 mmol) with m-chloroperoxybenzoic acid (20 mg, 0.08 mmol) in CH2Cl2 (0.9 mL) at 0 ° C for 1 hour. The reaction was chromatographed directly on silica gel eluting with a gradient of acetone to 30% acetone / MeOH to give the isomer title compounds (±) - (2R, 3S, 5R, 1'S, 3'R) (yield :. 010 g, 27%) and isomer (±) - (2R, 3S, 5R, 1'S, 3'S) (yield: .011 g, 29%). , ^ ^ ^ ^ 165B (+) - (2R, 3S, 5R, 1'S, 3'R) -2- (1-Acetamido-2- (Nm ethyl- Nt-bu ti lam-N-oxide)) eti I hydrochloride salt -3- vi or I- pyrro lid i n-5-carboxylic acid The title compound was prepared according to the method described in Example 15C using (±) - (2R, 3S, 5R) t-butyl ester , 1'S, 3'R) -1-f-butoxycarbonyl-2- (1-acetamido-2- (N-methyl-Nt-butylamino-N-oxide)) ethyl-pyrrolidine-5-carboxylic acid instead of t-butyl (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidine-5-carboxylic acid ester (yield: 6 mg) , 80%). 1H NMR (CD3OD) d 5.72-5.87 (m, 1H), 5.40 (d, 1H), 5.20-5.28 (m, 2H), 4.44-4.53 (dd, 1H), 3.73-3.95 (m, 3H), 3.57 (s, 3H), 3.08-3.19 (m, 1H), 2.59-2.72 (m, 1H), 2.05-2.15 (m, 1H), 2.04 (s, 3H), 1.54 (s, 9H). MS. (M + H) * = 328 Examples 166-178 The following title compounds were prepared from according to the method described in Example 165.

Example 166 Acid hydrochloride salt (±) - (2R.3S, 5R.1'S, 3'R) -2- (1-Acetamido-2- (N-methyl-N-isopropylamino-N-oxide)) ethyl-3-vinyl -pyrrolidine-5-carboxylic acid 1H NMR (MeOD-d3) 55.87-5.74 (m, 1H), 5.46-5.40 (m, 1H), 5.27-5.23 (m, 1H), 5.21-5.18 (m, 1H), 4.50 (dd, J = 8.1, 9.8Hz, 1H), 4.04-3.87 (m, 4H), 3.54 (s, 3H), 3.20-3.14 (m , 1H), 2.69-2.60 (m, 1H), 2.12- 2.01 (m, 1H), 2.05 (s, 3H), 1.50 (d, J = 6.4Hz, 3H), 1.48 (d, J = 6.4Hz, 3H). MS: (M + H) + = 314, (M + Na) + = 336, (2M + 1) + = 627, (2M + Na) + = 649. Example 167 Acid hydrochloride (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-Acetamido-2- (N-methyl-N-propylamine and non-N-oxide-3-vinyl-pyrrolidine -5-carboxylic acid 1H NMR (MeOD-d3) d 5.87-5.74 (m, 1H), 546-5.40 (m, 1H), 5.27-5.23 (m, 1H), 5.21-5.18 (m, 1H), 4.50 (dd, J = 8.1, 9.8Hz, 1H), 4.04-3.87 ^^^ (m, 4H), 354 (s, 3H), 3.20-3.14 (m, 1H), 269-2.60 (m, 1H), 2.12-2.01 (m, 1H), 2.05 (s, 3H), 1.50 (d , J = 64Hz, 3H), 1.48 (d, J = 6.4Hz, 3H). MS- (M + H) * = 314, (M + H-H20) "= 295 Example 168 Acid hydrochloride salt (±) - (2R.3S.5R.1'S.3'S) -2- (1-Acetamido-2- (N-methyl-N-ethylamino-N-oxide)) ethyl-3-vinyl-pyrrolidine -5-carboxylic acid 1H NMR (MeOD-d3) G_ 5.82-5.75 (m, 1H), 5.44 (d, J = 17.1Hz, 1H), 5.26 (d, J = 10.4Hz, 1H), 5.14-5.11 (m , 1H), 4.48-4.45 (m, 1H), 4.9 (d, J = 4.9Hz, 2H), 3.87 (d, J = 4.9, 10.4Hz, 1H), 3.76 (q, J = 6.7Hz, 2H) , 3.54 (s, 3H), 3.17-3.09 (m, 1H), 2.68-2.62 (m, 1H), 2.06 (s, 3H), 2.09-2.03 (, 1H), 1.45 (t, J = 7.3Hz, 3H). MS: (M + H) * = 300, (M + Na) * = 322, (M + H-H20) * = 282 Example 169 Acid hydrochloride salt (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (N, N di meti lami non-N-oxide) ethyl-3-vi nyl-pyrrole id n-5-carboxylic 1 H NMR (DMSO-de) 5 8.58 (d, 1H), 5.67-5.78 (m, 1H), 5.20 (d, 1H) 5.08 (d, 1H), 4.62-4.78 (brm) , 1H), 4.25-4.42 (brm, 1H), 4.06 (d, 1H) 3.85-3.95 (brm, 1H), 3.88-3.98 (brm, 1H), 3.35-3.50 (brs, 6H), 2.36 2.48 (m , 1H), 1.92 (m, 1H), 1.85 (s, 3H) MS: (M + H) * = 286 Example 170 Acid hydrochloride (±) - (2R, 3S, 5R, 1'S.3'S) -2- (1-Acetamido-2- (N-methyl-N-benzylamino-N-oxide)) ethyl-3-v? Nil -pyrrolidine-5-carboxylic acid 1H NMR (MeOD-d3) 57.60-7.47 (m, 5H), 5.75-5.65 (m, 1H), 5.39 (d, J = 6. 35Hz, 1H), 5.21 (d, J = 8.8Hz, 1H), 5.18-5.11 (m, 1H), 5.00-4.70 (m, 2H), 4.35-4.27 (m, 1H), 4.00-3.94 (m, 2H), 3.86-3.79 (m, 1H), 3.20 (s, 3H), 3.14-3.05 (m, 1H), 2.77-2.50 (m, 1H), 2.08 (s, 3H), 2.10-2.94 (m, 1H).

«= Ntft-aiaMfai MS. (M + H) * = 362, (M + Na) * = 385, (M-H) "= 360, (M + 35) = 396 Example 171 Acid hydrochloride salt (±) - (2R.3S.5R.1'S.3'S) -2- (1-Acetamido-2- (N-methyl-Nt-butylamino-N-oxide) ethyl-3-vinyl-pyrrolidin- 5-carboxylic acid 1H NMR (CD3OD) d 5.80 (m, 1H), 5.44 (d, 1H), 5.27 (d, 1H), 5.08 (m, 1H), 4.34-4.44 (dd, 1H), 3.83- 3.94 (, 3H), 3.38 (s, 3H), 3.02-3.18 (m, 1H), 2.58-2.72 (m, 1H), 2.08 (s, 3H), 1.97-2.08 (m, 1H), 1.55 (s) 9H) MS: (M + H) * = 328 Example 172 Acid hydrochloride (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-Acetamido-2- (N-methyl-N-isopropylamino-N-oxide)) ethyl-3-vinyl-pyrrolidine -5-carboxylic acid 1H NMR (MeOD-d) 5 5.86-5.74 (m, 1H), 5.53-5.47 (m, 1H), 5.29-5.25 (m, 1H), 5.22-5.19 (, 1H), 4.50 (dd) , J = 8 1, 9.5Hz, 1H), 4.13-4.04 (m, 2H), 396 (dd, J = 4.1, 10.5Hz, 1H), 3.87-3.82 (m, 1H), 3.39 (s, 3H), 3.23-3.17 (m, 1H), 2.70-2.61 (m , 1H), 2.11 (s, 3H), 2.08-2.00 (m, 1H), 1.50 (d, J = 6.4Hz, 3H), 1.49 (d, J = 6.4Hz, 3H). MS: (M + H) + = 314, (M + Na) + = 336, (2M + 1) + = 627, (2M + Na) + = 649.

Example 173 Acid hydrochloride salt (± 1- (2R.3S, 5R, 1'S, 3'R) -2- (1-Acetamido-2- (N-methyl-N-propylamino-N-oxide)) ethyl-3-vinyl -pyrrolidine-5-carboxylic acid H NMR (MeOD-d3) 6 5.82-5.75 (m, 1H), 5.45 (d, J = 17.1Hz, 1H), . 26 (d, J = 10.4Hz, 1H), 5.07-5.13 (m, 1H), 4.48-4.42 (m, 1H), 3.98 (d, J = 5.5Hz, 2H), 3.86 (dd, J = 4.3, 9.8Hz, 1H), 3.67-3.64 (m, 2H), 3.46 (s, 3H), 3.16-3.01 (m, 1H), 2.68-2.62 (m, 1H), 2.09-2.02 (m, 1H), 2.06 (s, 3H), 1.92-1.86 (m, 2H), 1.04 (t, J = 7.3Hz, 3H). MS: (M + H) * = 314, (M + H-H20) "= 295 Example 174 Acid hydrochloride salt (±) - (2R.3S.5R.1'S.3'R) -2- (1-Acetamido-2- (Nm eti I- N -ethyl to mino-N-oxide)) eti l- 3-vi N-pyrrolidin-5-carboxylic H NMR (MeOD-d3) 5 5.82-5.75 (m, 1H), 5.45 (d, J = 17.1Hz, 1H), . 26 (d, J = 10.4Hz, 1H), 5 13-5.10 (m, 1H), 4.48-4.44 (m, 1H), 4.02-3.94 (m, 2H), 3.89 (dd, J = 4.3, 9.8Hz , 1H), 3.82 (q, J = 7.3Hz, 2H), 3.46 (s, 3H), 3.18-3.10 (m, 1H), 2.68-2.62 (m, 1H), 2.09 (s, 3H), 2.07- 2.02 (m, 1H), 1.46 (t, J = 7.3Hz, 3H). MS: (M + H) * = 300, (M + Na) * = 322, (M + H-H20) * = 282 Example 175 Acid hydrochloride (±) - (2R, 3S, 5R.1'S, 3'S) -2- (1-Acetamido-2- (N-methyl-N-benzylamino-N-oxide)) ethyl-3-vinyl-p Rhodine din-5-carboxylic acid 1 H NMR (MeOD-d 3) 5 7.60-7.47 (m, 5H), 5.75-5.65 (m, 1H), 5.39 (d, J = 6.35Hz, 1H), 5.21 (d, J = 8.8Hz, 1H), 5.18-5.11 (m, 1H), 5.00-4.70 (m, 2H), 4.35-4.27 (m, 1H), 4.00-394 (m, 2H), 3.86-3.79 (m, 1H), 3.40 (s, 3H), 3.14-305 (m, 1H), 2.77-250 (m, 1H), 2.08 (s, 3H), 2.10-2.94 (m, 1H) MS: (M + H) * = 362, (M + Na) * = 385, (MH) = 360, (M + 35) "= 396 Example 176 Acid hydrochloride salt (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-2- (NN-diethylamino-N-oxide)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR (MeOD-d3) 5 5.84-5.78 (m, 1H), 5.45 (d, J = 16.85Hz, 1H), 5.26 (d, J = 10.0Hz, 1H), 5.09-5.05 (m, 1H), 4.45- 4.42 (m, 1H), 3.96-3.86 (m, 3H), 3.76 (q, J = 6.6Hz, 2H), 3.70 (q, J = 7.3Hz, 2H), 3.15-3.11 (m, 1H), 2.68 -2.62 (m, 1H), 2.08-2.02 (m, 1H), 2.08 (s, 3H), 1.44-1.38 (m, 6H). MS: (M + H) * = 314, (M + Na) * = 336, (M + 2Na) * = 358 is & tf Example 177 Acid hydrochloride (±) - (2R.3S, 5R.1'S.3'R) -2- (1-Acetamido-2- (N-pyrrolidinyl-N-oxide)) ethyl-3-vinyl-pyrrolidin-5 -carboxylic H NMR (DMSO-de) d 8.74 (d, 1H), 5.65-5.80 (m, 1H), 5.28 (d, 1H), 5.10 (d, 1H), 4.82 (m, 1H), 4.40-4.50 (dd, 1H), 4.30 (d, 1H), 3.60-4.12 (brm, 5H), 2.98-3.15 (m, 1H), 2.38-2.48 (, 1H), 2.05-2.20 (brm, 5H), 1.88- 1.98 (m, 1H), 1.87 (s, 3H). MS: (M + H) * = 312 Example 178 (T) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2- (N-morpholinyl-N-oxide) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 1H NMR hydrochloride salt ( DMSO-de) d 8.65 (d, 1H), 5.66-5.80 (m, 1H), 5.22 (d, 1H), . 09 (d, 1H), 4.78 (brs, 1H), 4.32-4.42 (dd, 1H), 4.10-4.17 (brm, 2H), 3. 50-4.02 (brm, 9H), 2.92-3.04 (brm, 1H), 2.37-2.48 (m, 1H), 1.88-1.96 (m, 1H), 1.87 (s, 3H). MS: (M + H) * = 328 Example 179 Acid hydrochloride salt (±) - (2R.3S.5R.1'S.3'S) -2- (1-Acetamido-2- (N-et? LN-methylamino-N-oxide)) ethyl-3- ( c / s-propen-1-yl) -p-rrolidin-5-carboxylic acid 179A (+.) - (2R, 3S.5R, 1'S) -1-f-Butoxycarbonyl-2-oxiranyl-3- (c / s-propen-1-yl) -pyrrolidin-5 acid t-butyl ester carboxylic The title compound was prepared according to the method described in Example 1231, but using ethyltriphenylphosphonium bromide instead of methyltriphenylphosphonium bromide (yield: 350 mg, 77%). 1H NMR (CDCU) (rotamers) d 5.55-5.43 (m, 2H), 4.13-4.04 (m, 2H), 3. 14-3.11 (m, 2H), 2.76-2.50 (m, 3H), 1.75-1.70 (m, 1H), 1.64 (d, 3H), 1.48-1.43 (m, 18H). MS: (M + H) * = 354, (M + Na) * = 376, (2M + Na) * = 729 179Bt-butyl ester of (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2-f1-methanesulfonyloxy-3-azido) ethyl-3- (cs-propen-1) -yl) -pyrrolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 123J, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2-oxiranyl- t-butyl ester. 3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2-t-butyl ester (1-Acetamido) butyl-3-vinyl-pyrrolidine-5-carboxylic acid (yield: 1.08 g, 84%). 1H NMR (DMSO-de) (rotamers) d 5.53-5.33 (m, 2H), 5.05-4.93 (m, 1H), 4.20-3.90 (m, 2H), 3.76-3.62 (, 2H), 3.24 (s, 3H), 2.59-2.49 (m, 1H), 1.64-1.55 (m, 5H), 1.43-1.36 (m, 18H). MS: (M + H) * = 475, (M + Na) * = 497, (2M + Na) * = 971 179C t-butyl ester of (±) - (2R, 3S.5R.1 'S) -1-f-Butoxycarbonyl-2-aziridinyl-3- (c; s-propen-1-yl) -pyrrolidine -5-carboxylic acid. The title compound was prepared according to the method described in Example 123K, but using (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-methanesulfonyloxy-3-azido) ethyl 3- (c / 's-propen- 1-yl) -pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1 'S) -1-f-butoxycarbonyl-2- (1-methanesulfonyloxy-3-az? Do) ethyl-3-vinyl- pyrrolidine-5-carboxyl? co (crude yield: 564 mg, 71%). 1H NMR (DMSO-dß) (rotamers) d 5.45-5.30 (m, 2H), 4.15-3.99 (m, 1H), 3.30-3.08 (m, 1H), 3.07-2.84 (m, 1H), 2.68-2.51 (m, 1H), 2.13-1.85 (m, 1H), 1.80-1.05 (m, 3H), 1.57 (d, J = 5.4Hz, 3H), 1.41-1.35 (m, 18H). MS: (M + H) * = 352, (M + 23) * = 375, (2M + H) * = 705, (2M + 23) * = 727 179D t-butyl ester of f ±) - (2R.3S.5R.1 'S) -1-f-Butoxycarbonyl-2- (N-acetylaziridinyl) -3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 123L, using t-butyl ester (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2-aziridinil- 3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2 R, 3S, 5 R, 1'S) - 1-f-butoxycarbonyl- t-butyl ester 2-aziri din il-3- vi ni l-pyrrolidi n-5-carboxylic acid (yield: 455 mg, 72%). 1H NMR (DMSO-de) (rotamers) 5 5.7 -5.34 (m, 2H), 4.17 (dd, J = 2.4, 6.35Hz, 1H), 3.41 (dd, J = 1.95, 6.35Hz, 1H), 3.14- 2.99 (m, 1H), 2.73- 2.58 (m, 2H), 2.40 (d, J = 6.35Hz, 1H), 2.17-2.12 (m, 1H), 2.05-2.00 (m, 3H), 1.66-1.55 (m, 1H), 1.56 (d, J = 68Hz, 3H), 1.41-1.31 (m, 18H).

MS: (M + H) * = 395, (M + Na) * = 417, (M + H + Na) * = 418, 179E (±) - (2R, 3S.5R.1'S) -1-f-Butoxycarbonyl-2- (1 -acetamido-2-N-ethyl-N -methylamine) t-butyl ester et? L -3- (cs-propen-1-yl) -pyrro lid i-5-carboxylic acid. The title compound was prepared according to the method described in Example 150, but using N-ethyl-N-methyl-amine instead of diethylamine (yield: 30 mg, 87%). MS: (M + H) * = 454, (M + Na) * = 476, (M-H) '= 452, (M + 35)' = 488 179E t-butyl ester of acid (±) - (2R.3S, 5R.1'S.3'R) and (±) - (2R.3S. 5R.1'S, 3'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2- (N-ethyl-N-methylamino-N-oxido)) etl-3- (cs-propen-1 -yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 165A, using (±) - (2R, 3S, 5R, 1'S) -1 t-butyl ester -f-butoxycarbonyl-2- (1-acetamido-2- (N-ethyl-N-methylamino)) ethyl-3- (c / s-propen-1-yl) -pyrrolidin-5- carboxylic acid instead of t-butyl ester (±) - (2R, 3S.5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-N-methyl-Nf-butylamino) ethyl-3 - (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 15.2 mg, 51%).

Acetamido-2- (N-ethyl-N-methalamino-N-oxido)) ethyl-3- (c > s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 1K, using (±) - (2R, 3S, 5R, 1'S, 3'R) -1-f-butoxycarbonyl-2- (1-acetamido) t-butyl ester -2- (N-Methyl-N-ethyl-N-oxide)) ethyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2-t-butyl ester 1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 8.7 mg, 29%). 1H NMR (MeOD-dj) d 5.75-5.69 (m, 1H), 5.37-5.30 (m, 1H), 5.07-5.04 (m, 1H), 4.49 (dd, J = 7.8, 10.2Hz, 1H), 4.05 -3.74 (m, 4H), 3.61-3.32 (m, 1H), 3.55 (s, 3H), 2.69-2.60 (m, 1H), 2.04 (s, 3H), 1.95-1.84 (m, 1H), 1.75 (dd, J = 2.0, 7.1Hz, 3H), 1.44 (t, J = 7.1Hz, 3H). MS: (M + H) * = 314, (M + 35) * = 348 Examples 179-184 The following compounds of the title were prepared from according to the method described in Example 179 Example 180 Acid hydrochloride salt (±) - (2R, 3S.5R, 1'S, 3'S) -2- (1-Acetamido-2- (N-eti I- -methyl amino-N-oxide)) eti l-3- ( c? 's-? ropen-1-yl) -pyrrolidine in-5-carboxylic acid 1H NMR (MeOD-d3) 5 5.75-5.69 (m, 1H), 5.38-5.30 (m, 1H), 5.02-4.98 (m, 1H), 4.47 (dd, J = 7.8, 9.8Hz, 1H), 4.02-3.77 (m, 4H), 3.56-3.39 (m, 1H), 3.47 (s, 3H), 2.69-2.59 (m , 1H), 2.07 (s, 3H), 1.95-1.84 (m, 1H), 1.76 (dd, J = 1.7, 7.1Hz, 3H), 1.46 (t, J = 7.1Hz, 3H). MS: (M + H) * = 314, (M + 35) * = 348 Example 181 Acid hydrochloride (±) - (2R, 3S.5R, 1'S, 3'R) -2- (1-Acetamido-2- (N- or propylN-methylamino or N-oxide)) eti l-3- (c / s-propen-1-yl) -pi rrol id n-5-carboxylic acid 'H NMR (MeOD-da) 5 5.76-5.66 (m, 1H), 5.39-5.31 (m, 1H), 5.17-511 (m, 1H) 451 (dd, J = 75, 10.2Hz, 1H), 4.07-3.76 (m, 4H), 3.55 (S, 3H), 3.52-3.39 (m, 1H), 2.69-2.60 (m, 1H), 2.02 (S, 3H), 208-1.84 (m, 1H), 1.75 (dd, J = 1.7, 7.1Hz, 3H), 1 50 (d, J = 6 1Hz, 3H), 1.48 (d, J = 6.4Hz, 3H), MS: (M + H) * = 314, (M + 35) * = 348 Example 182 Acid hydrochloride salt (±) - (2R.3S.5R, 1'S.3'S) -2- (1-Acetamido-2- (N-isopropyl-N-methylamino-N-oxide)) e ti I-3- ( cs- pro pen- 1-1 l) -pyrrolidone-5-carboxylic acid 1H NMR (MeOD-d3) d 5.76-5.68 (m, 1H), 5.39-5.31 (m, 1H), 5.10-5.05 (m, 1H), 4.49 (dd, J = 7.8, 9.8Hz, 1H), 4.12-3.84 (m, 4H), 3.55-3.44 (m, 1H), 3.41 (S, 3H), 2.69-2.60 (m , 1H), 2.08 (S, 3H), 2.07-1.84 (m, 1H), 1. 76 (dd, J = 1.7, 6.8Hz, 3H), 1.51 (d, J = 2.4Hz, 3H), 1.49 (d, J = 2.4Hz, 3H), MS: (M + H) * = 314, (M + 35) * = 348 Example 183 Acid hydrochloride salt (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-Acetamido-2- (N-isobuty I- Nm eti lam ino- N-óxy o)) ethyl-3- (cs- propen- 1-iD-p irol id i n-5-carboxylic acid 1H NMR (MeOD-d3) 5 5.75-5.69 (m, 1H), 5.38-5.31 (m, 1H), 5.18-5.12 (m , 1H), 4.53 (dd, J = 7.5, 9.8Hz, 1H), 4.25-342 (m, 6H), 365 (s, 3H), 2.68-2.58 (m, 1H), 2.44-2.36 (m, 1H) ), 2.05 (s, 3H), 1.94-1.87 (m, 1H), 1.76 (d, J = 2.7Hz, 3H), 1.14 (d, J = 6.8Hz, 6H) MS: (M + H) * = 342, (M + Na) * = 364, (MH) = 340 Example 184 Acid hydrochloride salt (±) - (2R.3S, 5R, 1'S.3'R) -2- (1-Acetamido-2- (N-isobutyl-N-methylamino-N-oxide)) ethyl-3- ( c / 's- propen-1-yl) -pi rrol id in-5-carboxylic acid 1 H NMR (MeOD-d 3) 5 5.75-5.69 (m, 1H), 5.38-5.31 (m, 1H), 5.06-5.02 ( , 1H), 4.48 (dd, J = 7.5, 9.8Hz, 1H), 408-385 (m, 3H), 3.70-3.57 (m, 2H), 352 (s, 3H), 3.48-3.41 (m, 1H), 2.70-2.60 (m, 1H), 2.40-2.36 (M, 1H), 2.08 (s, 3H), 1.95-1.84 (m, 1H), 1.75 (dd, J = 1.7, 7.1Hz, 3H), 1.14 (d, J = 6.8Hz, 6H). MS: (M + H) * = 342, (M + Na) * = 364, (M-H) '= 340 EXAMPLE 185 (+) - (2R.3S, 5R, 1'S) -2- (1-Acetamido-2- (N-isopropyl-N-hydroxyamino)) ethyl-3-vinyl-pyrrolidin-5-ca hydrochloride salt Ixil rbox 165A (±) - (2R.3S.5R, 1 'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2- (N-isopropyl-N-hydroxyamino)) ethyl ester t-butyl ester 3-vinyl-pyrrolidine-5-carboxylic acid. T-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f-Bu toxic acid rbonyl-2- (1-acetamide mido-2-isopro phenylamino) ethyl-3-vinyl- was dissolved. pyrrolidin-5-carboxylic acid (21 mg, 0.048 mmol) in 0.95 mL of acetone. Then it was titrated with 0.14 mL of a solution of dimethyldioxirane (0.1 M) in acetone at -45 ° C for 0.5 hour. The reaction was stopped by concentrating the mixture in vacuo. The residue was purified by chromatography on silica gel using 100% dichloromethane to 90% dichloromethane / methanol to give the title compound (yield: 5.3 mg, 24%) and recovering the starting material (yield 12 mg, 57%). 1 H NMR (MeOD-d 3) 6 5.95-5.89 (m, 1H), 5.08-4.94 (m, 2H), 4.75-4.68 (m, 1H), 4.13-3.83 (m, 2H), 2.85-2.47 (m, 4H), 1.96 (s, 3H), 1.82-1.76 (m, 1H), 1.52-1.44 (m, 18H), 1.45-1 29 (m, 1H), 1.07-1.04 (m, 6H). MS: (M + H) * = 456, (M + Na) * = 478, (M-H) = 454, (M + 35) - = 490. 185B (+) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2- (N-isopropyl-N-hydroxyamino)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride salt The title compound was prepared according to the method described in Example 1K, using (+) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-) t-butyl ester. acetamido-2- (N-isopropyl-N-hydroxyamino)) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of the (±) (2R, 3R, 5R, 1'S) t-butyl ester -2- ( 1-Acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidine-5-carboxylic acid (yield: 3.0 mg, 87%). 1 H NMR (MeOD-d 3) 5 5.83-5.71 (m, 1 H), 5.40 (d, J = 17.3 Hz, 1 H), . 24 (d, J = 10.2Hz, 1H), 4.48 (dd, J = 7.8, 10.2Hz, 1H), 3.88-3.59 (m, 4H), 3.17-3.10 (m, 1H), 2.67-2.58 (m, 1H), 2.10-1.99 (m, 1H), 2.09 (s, 3H), 1.33-1.17 (m, 1H), 1.38 (d, J = 6.4Hz, 6H). MS: (M + H) * = 300, (M-H) = 298, (2M-H) = 597 , a ^ js ^ .- Example 186 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetam id o-2-oxo-2-f-enyl) eti l-3- (cs- pro pen-1-yl) -pyridine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2 R, 3S, 5R, 1 'R, 2' S) -1-f-bu toxi carbon i l-2- (1 -ace tam id 0-2-0X0-2-phenyl) et L-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester) -1-f -butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / "s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 5.9 mg, 100%). 'H NMR (DMSO-dβ) 5 8.62 (d, J = 9.8Hz, 1H), 7.93 (, 2H), 7.68 (m, 1H), 7.55 (t, J = 7.9Hz, 2H), 5.61 (m, 1H), 5.48 (m, 1H), 5.19 (m, 1H), 4. 50 (m, 1H), 3.98 (t, J = 9.8Hz, 1H), 3.30 (m, 1H), 2.38 (m, 1H), 1.73 (m, 1H), 1.71 (s, 3H), 1.59 (m, 3H). MS: (M + H) * = 331, (M + Na) + = 353, (M-H) - = 329.

Example 187 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R.1'R, 2'R) -2- (1-Acetamido-2-methox-4-vinyl) butyl-3- (c s-propen-1-yl) -p-rrolidin-5-carboxylic acid. 187A (±) - (2R.3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1-acetamido-2-methoxy-4-vinyl) butyl ester 3- (c s-? Ropen-1-yl) -pyrrolidine-5-carboxylic acid. The title compound is prepared according to the method described in Example 84A, using (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy-4-vinyl) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (± ) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) bu ti l-3- (c? 'S-propen-1-) L) -rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrl 187B salt of acid trifluoroacetic acid (±) - (2R.3S, 5R.1'R.2'R) -2- (1-Acetamido-2-methoxy-vinyl) butyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1) t-butyl ester 'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-4-vinyl) butyl-3- (c;' s-propen-1-yl) -pyrrolidin- 5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3-butyl ester - (c? s-propen-1-yl) -pyrrolidine-5-carboxylic acid.

Example 188 Salt of the acid trifluoroacetic acid (+.) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetate mido-2-methoxy-4-vinyl) butyl-3- (cs-propen- 1-yl) -pyrrole-n-5-carboxylic acid. 188A (+) - (2R.3S.5R.1'R.2'S) t-butyl ester -1-f- Butoxycarbonyl-2- (1-acetamido-2-methoxy-4-vinyl) butyl-3- (cs-propen-1-yl) -pyrrolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 84A, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) -butyl ester. 4- vinyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R, 2) t-butyl ester , S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0044 g, 22 %). MS: (M + H) * = 481, (M-H) - = 479. 188B Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R, 2'S) - 2- (1-Acetamido-2-methoxy-4-vinyl) butyl-3- (c / s-propen-1-yl) -? -rololidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2 R, 3S, 5R, 1 'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetam id o-2-methoxy-4-vinyl) butyl-3- (c s) -propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1) Acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0031 g, 100%). 20 1 H NMR (DMSO-de) d 7.93 (d, J = 9.2Hz, 1H), 5.81 (m, 1H), 5.49 (m, 1H), 5.26 (m, 1H), 5.1-4.9 (m, 2H) , 4.29 (m 1 H), 4.03 (m, 2H), 3.68 (m, 1H), 3.26 (m, 1H), 3.25 (s, 3H), 3.18 (quint., J = 8.5Hz, 1H), 2.40 ( dt, J = 12.7.7.3Hz, 1H), 2.32 (M, 1H), 2.20 (m, 1H), 2.02 (m, 1H), 1 85 (s, 3H), 1.68 (m, 1H), 1.64 (m, 1H), 1 61 (dd, J = 6.7.1.8Hz, 3H), 1.55-1.40 (m, 2H). MS: (M + H) * = 325, (M + Na) * = 347, (M-H) '= 323.

EXAMPLE 189 Salt of trifluoroacetic acid of (±) - (2R.3R, 5R, 1'R, 2'S) -2- (1-Acetamido-2,3-dihydroxy) propyl-3- (c / s-propen-1-) il) -pyrrolidine-5-carboxylic acid 189A (±) - (2R, 3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-methane-sulfonyl-loxi-3-azido) -ethyl-3-f-bu-bu ethyl acid t-butyl ester eni Isyloxymethyl-pyrrolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 123J using acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2-oxirane-3-f-butyldiphenyl-silyloxymethyl-pyrrolidine-5-carboxylic acid instead of (2R, 3S, 5R, 1'S ) -2-oxiranyl-3-vinyl-pyrrolidine-5-carboxylic acid (yield: 9.0 g, 90%). 1 H NMR (DMSO-dβ) (rotamers) d 7.62-7.58 (m, 4H), 7.49-7.38 (m 6H), 4.97-4.79 (m, 1H), 4.19-4.02 (m, 2H), 3.79-3.48 (m m, 2H), 3.15 and 3. 13 (2s, 3H), 2.49-2.39 (m, 2H), 1.98-1.74 (m, 1H), 1.43-1.25 (m, 18H), 1.02 and 1.00 (2s, 9H) MS: (M + H) * = 703, (M + Na) * = 725 TBDPSO- P'Bu? Í 189B t-but? L acid ester (±) - (2R.3R.5R.1'S) -1-f-butox? Carbon? L-2-az? Pd? N? L-3-f-but? ld? phen? l? l? lox? met? lp? rrol? d? n-5-carbox? l? co The title compound was prepared according to the method described in Example 123K but using t-butyl acid ester (±) - (2 R, 3 R, 5 R, 1'S) - 1-f-butox? carbo ni l-2- (1-methanesulfon? lox? -3-az? do) et? l -3-f-but? Ld? Phen? Ls? L? Lox? Met? Lp? Rrol? D? N-5-carboxyl? Co instead of acid t-butyl ester (±) - (2R, 3S, 5R, 1'S) -1-f-butox? Carbon? L-2- (1-methanesulfon? Lox? -3-az? Do) et? L-3-v? N? Lp? Rrol? D? N-5 -carboxyl (yield 5 9 g, 79%) 1 H NMR (DMSO-de) (rotamers) 5 760-756 (m, 4H), 749-7 39 (m 6H), 4 11 -405 (m, 1H), 367-348 (m, 2H), 342-330 (m, 1H), 249-2 39 (m, 1H), 2 25-1 61 (m, 5H), 1 40, 1 35, 1 33, and 1 27 (4s, 18H), 099, and 098 (2s, 9H) MS (M + H) * = 581, (M + Na) * = 603 189Ct-butyl ester of acid (±) - (2R, 3R, 5R, 1'S) -1-f-Butox? Carbon? L-2-N-acet? Laz? R? D? N? L-3- f-but? ld? phen? ls? l? lox? met? lp? rrol? d? n-5-carbox? l? co The title compound was prepared according to the method described in Example 123L using acid t-butyl ester (±) - (2R, 3R 5R, 1'S) -1-f-butox? carbon? l-2-az? r? d? n? l-3-f-but? ld? phen ? l- s? l? lox? met? lp? rrol? d? n-5-carboxyl? co instead of acid t-butyl ester (±) - (2R, 3S, 5, 1'S) -1-f-butox? carbon? l-2-az? r? d? n? l-3-v? n? l? rrol? d? n-5-carboxilico (yield 3 1 g, 96%) 1 H NMR (DMSO-d?) ( rotamers) d 760-7 57 (m, 4H), 749-7 39 (m 6H), 4 18-4 11 (m, 1H), 371-351 (, 3H), 2 76-268 (m, 1H ), 2 58-245 (m, 1H), 246 and 2 39 (2d, J = 6 1, 6 1Hz, 1H), 240 and 2 47 (2m, 1H), 2 08 and 2 05 (2d, J = 3 1, 3 1 Hz, 1H), 202 and 1 99 (2s, 3H), 1 94-1 79 (m, 1H), 1 41, 1 36, 1 35 and 1 29 (4s, 18H), 099 and 098 (2s, 9H) MS (M + H) * = 623, (M + Na) * = 645 189T-butyl ester of (t) - (2R.3R.5R.1'R) -1-f-Butox? Carbon? L-2- (1-acetamido-2-acetox?) Et? l-3-f-but? ld? phen? ls? l? lox? met? l? rrol? d? n-5-carboxylic acid t-Butyl ester of (±) - (2R, 3R, 5R) was reacted , 1'S) -1-f-butox? Carbon? L-2-N-acet? Laz? Pd? N? L-3-f-but? Ld? Phen? Ls? L? Lox? Met? Lp? Rrol? d-n-5-carboxyl? co (275 g, 440 mmol) with potassium acetate (249 g, 2537 mmol) and acetic acid (1 45 mL, 2537 mmol) in DMSO (45 mL) at 100 ° C for 16 h. hours The reaction was set with 1N NaHCO 3 (100 mL) and diluted with ethyl acetate (300 mL). The organic layer was washed with water, and brine, dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified. by chromatography on silica gel using 100% dichloromethane at dichloromethane / 50% ethyl acetate to give the title compound (yield: 2.45g, 81%). MS: (M + H) * = 683, (M + Na) * = 705, (M-H) - = 681, (M + CI) - = 717 189E (±) - (2R.3R, 5R.1'R) -1-f-Butoxycarbonyl-2- (1 -acetamido-2-hydroxy) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine acid t-butyl ester -5-carboxylic acid (±) - (2R, 3R, 5R, 1'R) -1-f-Bu toxy carbon i-2- (1 -acetam-ido-2-acetoxy) acid was reacted. ) ethyl-3-f-butyl-phenyl Isyloxymethyl-pyrrolidine-5-carboxylic acid (2.45 g, 3.58 mmol) with potassium carbonate (1.48 g, 10.73 mmol) in methanol (18 mL) and THF (18 mL) at 25 ° C for 45 minutes. The reaction was set with water (100 L) and diluted with ethyl acetate (200 mL). The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using dichloromethane / 85% ethyl acetate to 100% ethyl acetate to give the title compound (yield: 2.05 g, 90%). MS: (M + H) * = 641, (M + Na) * = 663, (2M + Na + H) * = 1304, (M-H) "= 639, (M + CI) = 675 189F t-butyl ester of (±) - (2R, 3R, 5R.1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-formyl) ethyl-3-f-butyldiphen-lysilyloxymethyl- pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41A using (±) - (2R, 3R, 5R, 1'R) -1-f- t-butyl ester butoxycarbonyl-2- (1-acetamido-2-hydroxy) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R) t-butyl ester -1-f-Butoxycarbonyl 2- (1-acetamido-2-hydroxy) ethyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-de) (rotamers) 9.49 (d, J = 16.3, 1H), 8.33 and 8.29 (2d, J = 8.8 and 8.8Hz, 1H), 7.58-7.38 (m, 10H), 4.94 and 4.84 ( 2dd, J = 4.4, 8.8Hz and 4.4, 8.8Hz, 1H), 4.26-3.37 (m, 4H), 2.47-2.30 (m, 1H), 1.97-1.83 (m, 1H), 1.92 (s, 3H) , 1.42-1.18 (m, 18H), 1.42-1.18 (m, 1H), 1.00-0.97 (m, 9H). MS: (M + H) * = 639, (M-H) = 637 189G t-butyl ester of acid (±) - (2R.3R, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1 -acetam ido- 1- vi or I) meti I -3-f- bu ti I dif l i Isi lyloxim eti l-pyrrolidi n-5-carboxylic The title compound was prepared according to the method which is described in Example 118A using (±) - (2 R, 3 R, 5R, 1'R) - 1 - / - bu toxi carbon i-2- (1 -acetamide) acid t-butyl ester -2-form?) Eti I-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3S, 5R, 1'R) -1-f- t-butyl ester butoxycarbonyl 2- (1-acetamido-2-formyl) ethyl-3- (c s-propen-1-yl) -pyrrolidine-5-carboxylic acid. 'H NMR (DMSO-de) (rotamers) 7.99-7.74 (m, 1H), 7.59-7.39 (m, 10H), 5.80-5.68 (m, 1H), 5.21-5.01 (m, 3H), 3.97-3.31 (m, 1H), 3.78-3.74 (m, 1H), 3.60-3.46 (m, 2H), 2.53-2.37 (m, 1H), 2.09-1.72 (m, 1H), 1.87 (s, 3H), 1.42 -1.23 (m, 19H), 1.00-0.99 (m, 9H). 189H acid t-butyl ester (±) - (2R.3R.5R.1'R.2'R) and (±) - (2R, 3R, 5R, 1 'R, 2'S) - 1-f- Butoxica rbon il-2- (1-acetamido-2,3-dihydroxy) propyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid The title compounds were prepared according to the method described in Example 20A using acid t-butyl ester (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-vinyl) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidin-5 -carboxylic acid instead of (±) - (2R, 3S, 5R) -1-benzyl-2-vinyl-3-t-butyldimethyl-silyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester (±) - (2R, 3R, 5R, 1'R, 2'S) isomer (yield: 311mg, 24%) (±) - (2R, 3R, 5R, 1'R, 2'R) isomer (yield: 700 mg, 54% ). (±) - (2R, 3R, 5R, 1'R, 2'S) 1H NMR (DMSO-de) (rotamers) 7.62- 739 (m, 11H), 456 and 451 (d J = 48, 1H), 446-439 (m, 2H), 397-382 (m, 1H), 374-347 (m, 3H), 328-321 ( m, 2H), 289-264 (m, 1H), 251-245 (m, 1H), 205-1 8 (m, 1H), 1 87-1 86 (m, 3H), 1 43-1 23 (m, 19H), 099-098 (m, 9H) ( ±) - (2R, 3R, 5R, 1'R, 2'R) 1H NMR (DMSO-de) (rotamers) 763-740 (m, 11H), 456-454 (d, J = 48, 1H), 447-433 (m, 2H), 394-380 (m, 1H), 385-380 (m, 1H), 376-368 (m, 1H), 360-351 (m, 1H), 344-335 (m, 1H), 330-321 (m, 1H), 278-262 (m , 1H), 246-231 (m, 1H), 207-1 98 (m 1H), 1 83 (s, 3H), 1 39-1 29 (m, 19H), 1 00-099 (m, 9H) 1891 t-butyl ester of acid (±) - (2R.3R.5R.1'R.2'S) -1-f- Butox? Carbon? L-2- (1-acetamido-1- (2.2-d) ? met? l-1, 3-d? oxolan-4-? l)) met? l-3-f-but? ld? phen? ls? l? lox? met? lp? rrol? d? n-5 -carboxylic acid (±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-Butox? carbon? l-2- (1-) acetamido-2,3-d? h? drox?) prop? l-3-f-but? ld? phen? ls? l? lox? met? lp? rrol? d? n-5-carboxíl? co with 2,2-dimethoxypropane (11 mL, 909 mmol) and p-Toluenesulfonic acid (43 mg, 0023 mmol) in tetrahydrofuran (45 mL) at 25 ° C for 45 minutes. The reaction was set with tetylamine (3 mL). stirring was continued for 10 more minutes. The reaction was then diluted with 10% NaHCO3 (15 mL) and extracted with ethyl acetate (45 mL) The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was transferred to the next stage. Purified by chromatography on silica gel using 100% dichloromethane to 94% dichloromethane / methanol to give the title compound (yield, 194 mg, 91%). 189J acid t-butyl ester (±) - (2R.3R, 5R.1'R, 2'S) -1-f- Butoxycarbonyl-2- (1-acetamido-1- (2,2-dimethyl-l, 3-di-oxo-lan-4-yl)) methyl-10-3-hydroxymethyl pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 123G using (±) - (2R, 3R, 5R, 1'R, 2, S) t-butyl ester -1-f-butoxycarbonyl-2- (1-acetamido-1- (2,2- d -methyl 1-1, 3-d-oxolan-4-yl)) methyl-3-f-butyldiphenyl Loxymethyl-pyrrolidin-5-carboxylic acid in place of the (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2-oxiranyl-3-f-butyldiphenylsilyloxymethyl- t-butyl ester pyrrolidin-5-carboxylic acid. The resulting residue was purified by chromatography on silica gel using 100% dichloromethane to 94% dichloromethane / methanol to give the title compound (yield: 194 mg, 91%).

O ^ 189 JJ acid t-butyl ester (±) - (2R.3R.5R.1'R, 2 S) -1-f- Bu toxic rbop? L-2- (1-acetamido-1 - (2, 2-d? Met? Ll, 3-d? Oxolan-4-? L)) met? L-3-form? Lp? Rrol? D? N-5-carbox? L? Co The title compound was prepared from according to the method described in Example 123H using t-butyl ester of the acid (+) - (2R, 3R, 5R, 1'R 2 S) -1-f-butox? carbon? l-2- (1 -acetam-do-1- (2,2-d? met? l-1 3-d? oxolan-4-? l)) met? l-3-h? drox? met? lp? rrol? d? n -5-carbox Mico instead of t-butyl ester of acid (±) - (2R, 3R 5R, 1'S) -1-f-butox? Carbon? L-2-ox? Ran? L-3-h? Drox ? met? lp? rrol? d? n-5-carbox? l? co 189Kt-butyl ester of acid (±) - (2R.3S.5R.1'R.2'S) -1-f- Butox? Carbon? L-2- (1-acetamido-1- (2.2- d? met? l-1,3-d? oxolan-4-M)) met? l-3- (c / s-propen-1-yl)) - pyrrolidone-5-carboxy? The title compound was prepared according to the method described in Example 35A using acid t-butyl ester (±) - (2R 3R 5R, 1'R, 2'S) -1-f-butox? carbon? l-2- (1-acetamido-1- (22-d? met? l-1 3-d? oxolan-4-? l)) met? l-3-form? lp? rrol? d ? n-5-carbox? l? co in place of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester (yield- 11.5 mg, 59%). 1 H NMR (CDCU): d 6.62 (d, 1 H), 5.56 (m, 1 H), 5.40 (m, 1 H), 4.43 (m, 1 H), 4.25 (m, 1 H), 4.16 (m, 1 H), 4.02 (m, 1H), 3.88 (m, 1H), 3.54 (m 1H), 3.14 (m, 1H), 2.54 (m 1H), 2.04 (s, 3H), 1.71 (m 1H), 1.60 (dd, 3H) ), 1.46 (s, 9H), 1.45 (s, 9H), 1.40 (s, 3H), 1.32 (s, 3H). MS: (M + H) * = 483 189L salt of trifluoroacetic acid of (+) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamid 0-2, 3-dihydroxy) propyl-3- (c / s-propen -1-yl) -pi-1-yl-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R) t-butyl ester , 1'R, 2'S) - 1-f-butoxycarbonyl-2- (1 -acetamido- 1 - (2, 2-di methi 1-1, 3-dioxolan-4-yl)) methyl-3- (cs- propen-1-yl) -pyrrolidine-5-carboxylic acid in the place t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) butyl-3- (cs-propen-1-yl) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-dβ): d 7.84 (d, J = 9 Hz, 1 H), 5.49 (m, 1 H), 5.27 (m, 1 H), 4.47 (m, 1 H), 4.25 (m, 1 H), 4.17 ( m, 1H), 3.75 (m, 1H), 3.59 (m, 1H), 3.35 (m, 1H), 3.18 (m, 1H), 2.43 (m, 1H), 1.81 (s, 3H), 1.55 (dd , 3H). MS. (M + H) * = 287 Example 190 5 Salt of trifluoroacetic acid of (±) - (2R.3R.5R.1'R.2'R) -2- (1-Acetamido-2,3-dihydroxy) prop il-3- (c s) -propen-1- il) -pi rrol idi n-5-carboxylic 190A t-butyl ester of the acid (±) - (2R.3R.5R.1'R.2'R) -1-f- Butoxica rbon il-2- (1 -acetamido- 1 - (2.2-di) methyl-1,3-d-oxolan-4-yl)) methyl-3-f-butyldiphenyl-silyloxymethyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 1891 using t-butyl ester of acid 15 (±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2,3- dihydroxy) propyl- 3-f-butyl-phenyl-1-oxo-methyl-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'R, 2'S) t-butyl ester ) -1-f- B utoxycarbonyl-2- (1-acetamido-2,3-d ihi-hydroxy) propyl-3-f-butyldifen i-silyloxymethyl-pyrrolidine-5-carboxylic acid. 190B t-butyl ester of the acid (±) - (2R.3R, 5R.1'R.2'R) -1-f- Butoxica rboni l-2- (1 -acetamido- 1 - (2,2-di meti 1 -1.3-dioxolan-4-yl)) methyl-3-hydroxymethylpyrrolidine in-5-carboxylic acid The title compound was prepared according to the method described in Example 123G using t-butyl ester of (±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1 -acetamido- 1 - (2,2-dimethyl-1,3-dioxolan- 4-yl)) methyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2-t-butyl ester oxiranyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid. 190C t-butyl ester of acid (±) - (2R.3R.5R.1'R.2'R) -1-f-Bu toxic rbonyl-2- (1-acetamido-1- (2.2-dimethyl ti 1 -1.3-dioxo lan-4-yl)) methyl-3-formyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 123H using t-butyl ester of (±) acid - (2R, 3R, 5R, 1'R, 2'R) -1-i-butoxycarbonyl-2- (1-acetamido-1- (2,2- dimethyl-1, 3-dioxolan-4-yl)) methyl-3-hydrox? met? l-pyrroidip-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) t-butyl ester) -1-f-Butoxycarbonyl-2-oxiranyl-3-hydroxy-methyl-pyrrolidine-5-carboxylic acid. 190D t-butyl ester of the acid (±) - (2R.3S.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1 -acetamido- 1 - (2,2-d imethyl- 1,3-d ioxolan-4-D) methyl-3- (c / s-propen-1-yl)) - pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 35A using t-butyl ester of (±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-1- (2,2-di meti 1 -1, 3-d-ioxolan-4-yl)) methyl-3-p-pyrrolyl di-5-caboxylic acid in place of (±) - (2R, 3R, 5R, t-butyl ester, 1'S) -1-f-butoxycarbonyl-2- (1 -acetamido-3-methyl) buyl-3-form i I-pyrro lid i-5-carboxylic acid (yield: 42 mg, 61%). 1 H NMR (CDCU): 5 7.88 (d, 1 H), 5.52 (m, 1 H), 5.34 (m, 1 H), 4.33 (m, 1 H), 421 (m, 1 H), 3.96 (, 2 H), 3.83 (m, m, 1H), 3.60 (m, 1H), 3.40 (m, 1H), 2.53 (m, 1H), 1.98 (s, 3H), 1.66 (dd, 3H), 1.46 (s, 9H), 1.44 (s) , 9H), 1.41 (s, 3H), 1.33 (s, 3H). MS: (M + H) * = 483 íafaiB. 190Alpha trifluoroacetic acid (±) - (2R, 3S, 5R.1'R.2'R) -2- (1-Acetamido-2,3-di hydroxy) propyl-3- (c / s-propen -1-yl) -pi-r-idr-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2 R, 3S, t-butyl ester, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1 -acetamido- 1 - (2, 2-di methi 1-1, 3-d¡oxolan-4-yl)) methyl -3- (cis-propen-1-yl)) - pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester) -1 -fb or toxicarbon il-2- (1 -aceta mi do-2-hidroxy) buyl-3- (c / s-pro pen- 1 -i I) -pyrrolidine-5-carboxylic acid. 1 H NMR (DMSO-dβ): 5 7.98 (d, J = 9Hz, 1H), 5.48 (m, 1H), 5.29 (m, 1H), 4.60 (m, 1H), 4.30 (m, 1H), 4.12 ( m, 1H), 3.76 (m, 1H), 3.52 (m, 1H), 3.46 (m, 1H), 3.32 (m, 1H), 3.18 (m, 1H), 2.40 (m, 1H), 1.84 (s) , 3H), 1.60 (dd, 3H). MS: (M + H) * = 287 Example 193 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2-M-Acetamido-2-ethoxy) penti-3 (c / s-propen-1) -yl) -pyrrolidine-5-carboxylic acid 193A Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R.2'S) - 1 -f-Butoxycarbonyl l-2- (1 -acetamido-2-ethoxy) pentyl-3- ( c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 88A, but using ethyl iodide instead of methyl iodide (yield: 3.6 mg, 28%). MS: (M + H) * = 483, (M + Na) * = 505, (M-H) - = 481. 193B salt of the acid trifluoroacetic acid (+) - (2R.3S.5R.1'R.2'S) - 2- (1-Acetamido-2-ethoxy) pentyl-3- (cj's-propen-1-il) pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-ethoxy?) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester -1- f-butox? carbon? l-2- (1-acetamido-2-hydroxy) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 3.2 mg, 100%). 1 H NMR (DMSO-de) d 7.92 (d, J = 9.2Hz, 1H), 547 (m, 1H), 525 (m, 1H), 4.25 (m, 2H), 3.70 (m, 1H), 3.52 ( m, 1H), 3.33 (m, 2H), 3.18 (m, 1H), 2.39 (m, 1H), 1.85 (s, 3H), 1.66 (m, 1H), 1.61 (dd, J = 6.7, 1.8Hz , 3H), 1.56 (m, 1H), 1.37 (m, 1H), 1.28 (m, 2H), 1.13 (m, 3H), 0.86 (t, J = 7.3Hz, 3H). MS: (M + H) * = 327, (M + Na) * = 349, (M-H) - = 325.

Example 194 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R.2'R) -2- (1-Acetamido-2-ethoxy) pentyl-3- (c; s-propen- 1-yl) -pyrrolidin-5-carboxylic acid 194A (±) - (2R.3S.5R.1'R.2'R) -1-r- Butoxycarbon i-2- (1 -acetamido-2-ethoxy) pentyl- t-butyl ester 3- (c / s-pro pen- -iO-pyrrolidine-5-carboxylic acid) The title compound is prepared according to the method described in Example 88A, but using ethyl iodide instead of methyl-dimide. 194B acid (±) - (2R) trifluoroacetic acid salt, 3S, 5R, 1'R.2'RJ-2- (1- Ace tamido-2-ethoxy) pen til-3- (c / s-pro pen- 1 -yl) -pyrroli di n-5- carboxylic The title compound is prepared according to the method described in Example 41C, using (±) - (2 R, 3S, 5 R, 1'R, 2 'R) -1 t-butyl ester -f-bu toxica rbon il-2- (1 -acetam id o-2-ethoxy) pentyl-3- (c / s-propen-1-yl) -pyrrole-din-5-carboxylic acid instead of t-butyl acid ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c- 's-propen- 1-yl) -pyrrolidine-5-carboxyl? Co.

Example 195 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2-hydroxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (1) t-butyl ester. -acetamido-2-hydroxy) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester) -1-f -butoxycarbon? l-2- (1-acetamido-2-hydroxy) butl- 3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 19.9 mg, 100%) 1 H NMR (DMSO-de) d 7 80 (d, J = 8.8 Hz, 1 H), 5.76 (m, 1H), 5.23 (d, J = 17.1Hz, 1H), 5.15 (m, 1H), 4.31 (m, 1H), 4.03 (m, 1H), 3.62 (m, 5 1H), 3.53 (m , 2H), 2.79 (m, 1H), 2.42 (m, 1H), 1.90 (s, 3H), 1.85 (m, 1H). MS: (M + H) * = 243, (M + Na) * = 265, (M-H) - = 241.

EXAMPLE 196 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R, 2'S) -2- (1-Acetate-2-hydroxy-3-dimethylphosphoryl) propyl 3- (c / s-pro pen-1 -yl) -pyrrolidine-5-carboxylic acid 196A (+) - (2R.3S.5R.1'R.2'S) t-butyl ester and (±) - (2R, 3S, 5R, 1'R, 2'R) -1-f- Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-dimethylphosphonyl) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. Dr (t) -butyl ester of (±) - (2R, 3S, 5R, 1'R) -1- f- Butoxycarbonyl 2- (1-acetamido-1-formyl) methyl-3- (c / s-propen-1-yl) -20 pyrrolidine-5-carboxylic acid (78 mg, 0.19 mmol) in THF (5 mL) to a solution of dimethylphosphonylmethyl lithium (3M) (0.32 mL, 0.95 mmol) in THF (20 mL) at -78 ° C was reacted for 40 minutes. The reaction was set with water (10 mL) and saturated aqueous solution of ammonium chloride (10 mL) followed by extraction using dichloromethane (2 x 50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using 5-10% methanol in dichloromethane to give the title compounds (±) - (2R, 3S, 5R, 1'R, 2'R) isomer (yield: 27 mg, 27%) and (±) - (2R, 3S, 5R, 1'R, 2'S) isomer (yield: 5.5 mg, 6%). (±) - (2R, 3S, 5R, 1'R, 2'R) = 1H NMR (CDCU) d 5.98 (m, 1H), 5.58 (m, 1H), 5.35 (m, 1H), 4.94 (m , 1H), 4.14 (m, 2H), 3.74 (m, 8H), 3.06 (m, 1H), 2.64 (m, 1H), 2.03 (s, 3H), 1.95 (m, 1H), 1.83 (m, 3H), 1.53 (s, 9H), 1.46 (s, 9H) MS: (M + H) * = 535, (MH) "= 533 (±) - (2R, 3S, 5R, 1, R, 2'S) MS: (M + H) * = 535, (MH) = 533 196Sulfuric acid acetic acid (±) - (2R.3S, 5R, 1'R, 2'S) - 2- (1-Acetamido-2-hydroxyl-3-dimethylphosphonyl) propyl-3 (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2 R, 3S, 5 R, 1'R, 2'S) -1-f-bu toxicarbon i l-2- (1 -acetam ido-2-hid roxy- dimethylphosphonyl) propyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxyl? co in place of (±) - (2R, 3S, 5R, 1') t-butyl ester R, 2'S) - 1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy?) But? L-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 3 mg, 96%). 1 H NMR (DMSO-d 6) d 7.98 (d, J = 9.2 HZ, 1 H), 5.48 (M, 1 H), 5.28 (m, 1 H), 4.36 (m, 1 H), 4.30 (m, 1 H), 4.08 ( m, 2H), 3.70 (m, 2H), 3.60 (m, 6H), 3.18 (m, 1H), 2.40 (m, 1H), 2.05 (m, 1H), 1.85 (s, 3H), 1.60 (dd) , J = 6.2, 1.2 HZ, 3H) MS: (M + H) * = 379, (MH) "= 377 Example 197 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'R) -2- (1-Acetate mido-2-h id roxi-3-d metilf osf oni I) propi l-3- (cs-propen-1 -i D-pyrrolidin-5-carboxylic acid) The title compound was prepared according to the method described in Example 41C, using (±) - (-) t-butyl ester ( 2 R, 3S, 5 R, 1'R, 2'R) -1-f-butoxy carboni l-2- (1 -acetamido-2-hydroxy-dimethylphosphonyl) propyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1"R, 2'S) -1-f-butoxycarbonyl-2- (1-) t-butyl ester acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) - pyrrolidine-5-carboxylic acid (yield: 13 mg, 96%). 1 H NMR (DMSO-de) d 7.72 (d, J = 9.2 HZ, 1H), 5.48 (m, 1H), 5.24 (m, 1H), 4.44 (m, 1H), 4.15 (m, 2H), 3.62 (m, m, 7H), 3.54 (m, 1H), 3.15 (m, 1H), 2.40 (m, 1H), 1.95 (m, 1H), 1.82 (s, 3H), 1.72 (m, 1H), 1.54 (dd) , J = 6.7, 1.2 HZ, 3H) MS: (M + H) * = 379, (MH) "= 377 Example 198 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'S) -2- (1-Acetam-ido-3-hydroxy) propyl-3- (c / s-propen-1-yl) ) -pyrroli di n- 5- carboxy ico 198A (±) - (2R, 3S, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1 -acetam ido- 1- (c / s and frans-2-methoxyvinyl)) methyl t-butyl ester 3- (c / s-propen-1-yl) -pyridine n-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R) -1-f t-butyl ester -Bu toxicarbon il-2- (1 -acetamido-1-f ormyl) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (113 mg, 0.28 mmol) to a bromide solution of (methoxymethyl) triphenylphosphonium (240 mg, 0.70 mmol) and potassium t-butoxide (0.56 mL, 0.56 mmol, 1M in THF) in toluene (3 L) at 0 ° C for 15 minutes. The reaction was set up with saturated aqueous solution of ammonium chloride (3 mL) followed by extraction using dichloromethane (2 X 3 mL). The organic layer was dried over and? Süxz ^ zii & ^ x .. magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1/4 to give the title compounds 1H NMR (CDCU) 5 8.65 (br d, 1H) 6.01 (d, J = 5.7Hz, 1H ), 5.40 (m, 3H), 5.11 (br t, 1H), 4.15 (m, 2H), 3.72 (m, 1H) 3.61 (s, 3H), 3.00 (m, 1H), 2.42 (m, 1H) , 1.94 (s, 3H), 1.64 (dd, J = 1.4, 5.0Hz, 3H), 1.45 (m, 9H), 1.25 (m, 9H) MS: (M + H) * = 439. 198B (±) - (2R, 3S.5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-formyl) ethyl-3- (c; s-propen-1) acid t-butyl ester -yl) -pyrrolidine-5-carboxylic acid The t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f-Bu toxi carbon i-2- (1 -acetam ido-2- (c / 's and frans- 2-methoxyvinyl)) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (21 mg, 0.048 mmol) with LiBr (37 mg, 0.43 mmol) and ion exchange resin AG50W-X2 in CH3CN (2 mL) and water (0.1 mL) at room temperature for 45 minutes. The reaction was filtered and set with saturated aqueous sodium bicarbonate solution (1 mL) followed by extraction using dichloromethane (2 X 1 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1/4 to give the title compound. 1H NMR (CDCU) d 9.70 (dd, J = 1.3, 24Hz, 1H), 8.11 (d, J = 7.8Hz, 1H), 5.54 (m, 1H), 5.41 (t, J = 58Hz, 1H), 4.52 (m, 1H), 4.13 (dd, J = 4.4, 4.8Hz, 1H), 3.75 (dd, J = 2.7, 31Hz, 1H), 2.86 (, 1H), 2.47 (m, 3H), 1.99 (s, 3H), 1.63 (dd, J = 1.6, 5.1Hz, 3H), 1.46 (s, 9H), 1.45 (m, 1H), 1.44 (s, 9H) MS: (M + H) * = 425; (M-H) "= 423. 198C t-butyl ester of (±) - (2R.3S.5R.1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-3-hydroxy) propyl-3- (cjs-propen-1-yl) ) -pyrrolidone-5-carboxylic acid (±) - (2R, 3S, 5R, 1'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2) acid t-butyl ester was reacted -formyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (9 mg, 0.02 mmol) with sodium borohydride (1 mg, 0.02 mmol) in methanol (0.1 mL) at room temperature environment for 20 minutes. The reaction was set up with saturated aqueous solution of ammonium chloride (1 mL) followed by extraction using dichloromethane (2 X 1 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate / hexane 1/4 to give the title compound. 1H NMR (CDCU) 6 8.45 (d, J = 7.5Hz, 1H), 5.55 (m, 1H), 5.34 (t, J = 7.8Hz, 1H), 4.20 (dd, J = 30, 54Hz, 2H), 371 (d, J = 6.1Hz, 1H), 362 (m, 1H), 3.50 (t, J = 9.1Hz, 1H), 292 (m, 1H), 2.41 (m, 1H), 2.04 (s, 3H), 1.66 (dd, J = 2.0, 5.1Hz , 3H), 1.62 (m, 1H), 1.47 (s, 9H), 1.45 (m, 1H), 1.43 (s, 9H), 1.22 (m, 2H) MS: (M + H) * = 427; (M-H) '= 425. 198Drug of acid trifluoroacetic acid (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-hydroxy) propyl-3- (c / s-propen-1-yl) -pyrrolidin-5 -carboxylic The title compound was prepared according to the method described in Example 41C, using (±) - (2 R, 3S, 5 R, 1'S) t-butyl ester - 1-f-bu toxi carboni l-2- (1 -acetamido-2-h id roxi) propi I-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (± ) - (2R, 3S, 5R, 1'R, 2'S) - 1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c; 's-propen-1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 4.6 mg, 100%). 1 H NMR (DMSO-dβ) d 9.25 (br s, 1 H), 8.13 (d, J = 7.3 Hz, 1 H), 5.52 (m, 1 H), 5.28 (br t, 1 H), 4.32 (br t, 1 H) , 4.22 (m, 1H), 3.49 (m, 4H), 3.18 (m, 1H), 2.40 (m, 1H), 1.90 (s, 3H), 1.73 (m, 1H), 1.63 (dd, J = 1.8 , 5.5Hz, 3H), 1.57 (m, 1H) MS: (MH) - = 269; (M + H) * = 271.

Example 199 tpfluoroacético acid salt of (+) - (2R, 3S.5R.1'S, 3'S) -2- (1-Acetamido-3-hydrox?) Pentyl-3- (c s-propen-1-yl? ) -pyrroli in-5-carboxylic acid 199A (±) - (2R.3S.5R.1'S.3'S) t-butyl ester v (±) - (2R.3S.5R.1, R.3'R) -1-f-Butoxycarbonyl -2- (1-acetamido-3-hydroxy) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-ca rboxí lic was reacted t-butyl ester (±) - (2R , 3S, 5R, 1'S) -1-f-Bu toxic rboni l-2- (1-acetamido-2-formyl) ethyl-3- (c / s-pro pen- 1 -i I) -pyrrolidin- 5-carboxylic acid (26 mg, 0.061 mmol) with ethylmagnesium bromide (3.0 M) (0.122 mL, 0.367 mmol) in THF (4 mL) at room temperature for 30 minutes. The reaction was set up with saturated aqueous solution of ammonium chloride (10 mL) and water (10 mL) followed by extraction using ethyl acetate (3 X 25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 1/1 ethyl acetate / hexane followed by 2/1 ethyl acetate / hexane to give the title compounds (±) - (2R, 3S, 5R, 1'S, 2'S) (yield: 6.7 mg, 24%) and (±) - (2R, 3S, 5R, 1'S, 2'R) (yield: 6.8 mg, 24%). (±) - (2R, 3S, 5R, 1'S, 2, S) MS: (M + H) * = 455, (M + Na) * = 477, (MH) - = 453. (±) - (2R) , 3S, 5R, 1'S, 2'R) MS: (M + H) * = 455, (M + Na) * = 477, (MH) '= 453. 199B salt of trifluoroacetic acid of (+) - (2R.3S.5R.1'S, 3'S) -2- (1-Acetamido-3-hydrox?) Pentyl-3- (c / s-propen-1-yl) -p¡rrolidin-5-carboxylic acid the title compound was prepared according to the method described in Example 41C, using t-butyl ester (±) - (2 R, 3 S, 5 R, 1'S, 3'S ) -1-f-bu toxicarbon l-2- (1-ace tamido-3-hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t- butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid. ester (yield: 6.2 mg, 100%). 1 H NMR (DMSO-de) d 9.20 (bs, 1H), 8.18 (d, J = 7.3 Hz, 1H), 551 (m, 1H), 5.27 (m, 1H), 4.30 (m, 1H), 4.25 ( m, 1H), 3.58 (m, 1H), 3.41 (, 1H), 3.18 (m, 1H), 2.39 (m, 1H), 1.90 (s, 3H), 1.75 (m, 1H), 1.64 (dd, J = 7.5.1.5Hz, 3H), 1.51 (M, 1H), 1.38 (m, 1H), 1.32 (m, 1H), 0.83 (t, J = 7.3Hz, 3H). MS: (M + H) * = 299, (M + Na) * = 321, (M-H) "= 297, (2M-H)" = 595.

EXAMPLE 200 Salt of the acid tpfluoroacetic acid (±) - (2R, 3S.5R.1'S.3'R) -2- (1-Acetamido-3-hydroxy) pent? L-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2R, 3S, 5R, 1'S, 3'R) -1-f-butoxycarbonyl-2- (1-acetamido-3-hydroxy) pentyl-3- (c / s-propen-1-? ) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hi droxi) bu ti l -3- (c / s-propen-1-yl) -pyrrolidin-5-ca-rboxic. ester (yield: 6.5 mg, 100%). 1 H NMR (DMSO-de) d 9.25 (bs, 1H), 8.15 (d, J = 7.3 Hz, 1H), 5.52 (m, 1H), 5.27 (m, 1H), 431 (m, 2H), 352 (m, 1H), 3.36 (m, 1H), 3.19 (quint., J = 8.5Hz, 1H), 2.38 (m, 1H) , 1.92 (s, 3H), 1.75 (m, 1H), 1.64 (dd, J = 7.3.1.5Hz, 3H), 1.48 (m, 1H), 1.33 (m, 2H), 0.85 (t, J = 7.3Hz, 3H). MS: (M + H) * = 299, (M + Na) * = 321, (M-H) "= 297, (2M-H) = 595.

Eiemplo 201 tpfluoroacetico acid salt of acid f +) - (2R, 3S, 5R, 1'R) -2- (1- acetam do-2-oxo-3,3-d fluoro-3-v? N? ?) prop? l-3- (c / s-propen-1-? l) -pyrrol? d? n-5-carboxyl? co The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbon t-butyl ester? l-2- (1-Acetamido-2-oxo-3,3-d? fluoro-3-v? n? l) prop? l-3- (c / s-propen-1-? l) - pyrrolidone-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-bu toxic rbon 11 -2- (1 -aceta m? Do-2-hydrox?) But? L-3- (c / s-propen-1-? L) - ?? rrol? D? N-5-carboxyl? Co (yield 00050 g, 100%) 1 H NMR (DMSO-de) d 867 (d, J = 8 5 Hz, 1 H), 6 1-5 95 (m, 1 H), 5 78 (dd, J = 17 1, 24 Hz , 1H), 571 (d, 11 OHz, 1H), 545 (m, 1H), 5 12 (m, 1H), 4 94 (t, J = 92Hz, 1H), 451 (dd, J = 12 2, 6 1Hz, 1H), 3 98 (m, 1H), 324 (, 1H), 2 32 (m, 1H), 1 73 (s, 3H), 1 66 (q, J = 11 9Hz, 1H), 1 57 (dd, J = 67.1 8Hz, 3H) MS (M + H) * = 331, (M + H20) * = 349, (M + Na) * = 353, (MH) - = 329, (2M -H) = 659 Example 202 202A (±) - (2R.3R.5R, 1'R.2'S) t-butyl ester and (±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-Butoxycarbonyl -2- (1-Acetamido-2-hydroxy) butyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid The title compounds were prepared according to the method described in Example 41B using t-butyl ester of the acid (±) - (2R, 3R, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-f ormyl) ethyl-3-f-butyldiphenylsilyloxymethyl-pyrridin-5-carboxylic acid in Place of t-butyl ester of (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-formyl) ethyl-3- (c / s- propen-1-? l) -pyrrolidine-5-carboxylic acid to give isomer (+) - (2R, 3R, 5R, 1'R, 2'S) (yield: 370 mg, 17%) and isomer (±) - (2R , 3R, 5R, 1'R, 2'R) isomer (yield: 1.2 g, 55%). (+) - (2R, 3R, 5R, rR, 2'S) H NMR (d6-DMSO) d 7.4-7.65 (m, 10H), 4.47 (d, 1H), 4.32 (m, 1H), 3.87 (m, 2H), 3.68 (m, 1H), 3.55 (m, 1H), 3.25 (m, 1H), 2.7 (m, 1H), 2.45 ( m, 1H), 2.0 (m, 1H), 1.83 (d, 3H), 1.28-1.4 (m, 18H), 0.95 (d, 9H), 0.83 (dt, 3H) MS: (MH) - = 667, (M + 35) + = 703; (M + H) + = 669, (M + Na) + = 691 (+) - (2R, 3R, 5R, 1'R, 2, R) H NMR (d6-DMSO) d 7.4-7.65 (m, 10H), 4.40 (dd, 1H), 4.12-4.32 (, 1H), 3.82-396 (, 1H), 3.66 (m, 2H), 3.52 (t, 1H), 2 6-2.8 (m, 1H), 2 45 (m , 1H), 1.76-2.0 (m, 1H), 1.87 (d, 3H), 1 25-1 4 (m, 18H), O 95 (d, 9H), O 83 (dt, 3H) MS (MH) - = 667, (M + 35) + = 703, (M + H) + = 669, (M + Na) + = 691 202B t-butyl ester of (±) - (2R.3R.5R.1'R.2'S) -1-f- Butox? Carbon? L-2- (1-acetamido-2-methoxy) ? met? lox?) but? l-3-f-but? ld? phen? l? l? lox? met? l? rrol? d? n-5-carboxyl? acid t-butyl ester of the acid was reacted (±) - (2R, 3R, 5R, 1'R, 2'S) -1-f-butox? Carbon? L-2- (1-acetamido-2-hydrox?) But? L- 10 3 -f-but? ld? phen? l? l? lox? met? lp? rrol? d? n-5-carboxíl? co (0 58 g, 087 mmol) with methoxymethion chloride (1 15 mL, 1007 mmol) and diisopropylethylamine (3.5 L, 20 mmol) in diechloromethane (1 mL) at room temperature for 5 hours The reaction was set with saturated NH4Cl (100 mL) and diluted with ethyl acetate (200 mL) The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 5% methanol / methylene chloride to give the title compound (yield 064 g, 98%) 1 H NMR (d 6 -DMSO) d 74-765 (m, 10 H), 470 (s, 1 H), 462 (s, 1 H), 435-455 (, 2H), 375-395 (m, 2H), 368 (m, 1H), 3 55 (m, 1H), 325 (m, 1H), 324 (s, 3H), 2 55 (m, 1H), 245 (m, 1H), 2 0 (m, 1H), 1 85 (s, 3H), 1 28-1 4 (, 18H), 0 99 (d, 9H), 08 (dt) , 3H) MS (M-H) - = 755, (M + 35) + = 791, (M + H) + = 757, (M + Na) + = 779 202C t-butyl ester of the acid (±) - (2R.3R.5R.1'R.2'S) -1-f- 5 Butoxy carbo n? L-2- (1 -acetam? Do-2-methox) ? met? lox?) bu t? l-3-h id roxi metí-p? rrol? d? n-5-carbox? l? co The title compound was prepared according to the method described in Example 123G using acid t-butyl ester (±) - (2R, 3R, 5R, 1'R, 2'S) -1-f-butox? Carbon? L-2- (1-acetamido-2-methox? -10 methox?) But? l-3-f-but? ld? phen? ls? hlox? met? lp? rrol? d? n-5-carbox? l? co instead of acid t-butyl ester (±) - (2R, 3R , 5R, 1'S) -1-f-butox? Carbon? L-2-ox? Ran? L-3-f-but? Ld? Phen? Ls?!? Lox? Met? Lp? Rrol? D? N- 5-carboxylic (yield 0416 g, 95%) 1 H NMR (d 6 -DMSO) 6 745 (t, 1 H), 462-474 (m, 3 H), 448 (, 1 H), 15 385 (m, 2H), 3 55-36 (m, 2H), 345 (t, 1H), 32-34 (m, 2H), 325 (d, 3H), 2 4 (m, 2H), 1 82 (d, 3H), 1 58 (m, 3H), 1 32-1 45 (m, 18H), 082 (dt, 3H) MS (M-H) - = 517, (M + 35) + = 553, (M + H) + = 519, (M + Na) * = 541 202D t-butyl ester of (±) - (2R.3R, 5R.1'R.2'S) -1-f- Butoxycarbonyl-2- (1 -acetamido-2-methoxy-pyrroxy) butyl-3-form I-pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 123H using (±) - (2R, 3R, 5R, 1'R, 2'S) t-butyl ester -1-f-Butoxycarbonyl-2- (1-acetamido-2-methoxymethyloxy) butyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) t-butyl ester ) -1-f-butoxycarbonyl-2-oxiranyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid (yield: 0.335 g, 80.8%). 1H NMR (d6-DMSO) d 9.55 (d, 1H), 7.48 (m, 1H), 4.55-4.72 (m, 4H) 3. 9 (d, 1H), 3.6 (m, 2H), 3.45 (m, 3H), 3.32 (s, 3H), 3.05 (t, 1H), 2.25-2.45 (m, 4H), 1.83 (s, 3H) , 1.58 (m, 3H), 1.30-1.45 (m, 18H), 0.86 (dt, 3H). MS: (M-H) - = 515, (M + 35) + = 551; (M + H) + = 517 202E t-butyl ester of (±) - (2R.3R.5R.1'R.2'S.1"RS) -1-r- B utoxycarbonyl-2- (1 -acetamido-2-methoxymethyl loxy) ) butyl-3- (1-hydroxy-2-propyn-yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 38A using acid t-butyl ester ( ±) - (2R, 3R, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3-formyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-formyl-pyrrolidine-5-carboxylic acid t-butyl ester ( yield: 0.27 g, 83%). MS: (M-H) - = 541, (M + 35) + = 577; (M + H) + = 543, (M + Na) * = 565 202F t-butyl ester of the acid (+.) - (2R.3R.5R, 1'R.2'S) -1-f- Toxic Bu rbonyl-2- (1-a-cetamido-2-me toxymethyloxy) butyl- 3- (1-Oxo-2-propyn-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 38B using acid t-butyl ester (±) - (2R, 3R, 5R, 1'R, 2'S, 1 RS) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxymethyloxy) butyl-3- (1-hydroxy) 2-propin-1-yl) -pyrrole-din-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1 'S, 1"RS) -1-f-bu t-butyl ester toxi carbon l-2- (1 -acetamido-3-methyl) bu ti l-3- (1-hydroxy-2-propin-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.2 g, 74 %). 1H NMR (d6-DMSO) 67.49 (br d, 1H), 5.0 (d, 1H), 4.7 (br s, 1H), 4.55-4.7 (, 3H), 3.88 (br d, 1H), 3.5 -3.7 (m, 2H), 3.43 (t, 2H), 3.2-3.4 (m, 2H), 3.24 (s, 3H), 2.4-2.7 (m, 2H), 1.84 (s, 3H), 1.5-1.7 (m, 2H), 1.30-1.45 (m, 18H), 0.86 (dt, 3H) MS: (MH) '= 539, (M + 35) + = 575; (M + H) + = 541, (M + Na) * = 563 202G t-butyl ester of the acid (+.) - (2R.3R.5R.1'R.2'S) -1-f- B or toxicarbon il-2- (1 -acetam ido-2-methoxy methyloxy) butyl -3- (pi-razol-3-i I) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 38C using (+) - (2R, t-butyl ester, 3R, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3- (1-oxo-2-propin-1-yl) -pyrrolidin- 5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) butyl-3-butyl ester (1-oxo-2-propin-1-yl) -pyrrolidin-5-carboxyMeo (yield: 180 mg, 87%). 1 H NMR (d 6 -DMSO) d 7.57 (br t, 2 H), 6.1 (d, 1 H), 4.50-4.7 (m, 4 H) 3. 95 (m, 1H), 3.4-3.6 (m, 3H), 3.3-3.4 (m, 3H), 3.22 (d, 3H), 2.55-2.65 (m, 1H), 2.2 (m, 1H), 1.85 ( s, 3H), 1.5-1.7 (m, 2H), 1.15-1.45 (m, 18H), 0.86 (dt, 3H). MS: (M-H) - = 553, (M + 35) + = 589; (M + H) + = 553, (M + Na) * = 577 202H salt of the acid trifluoroacetic acid (±) - (2R.3R.5R.1'R, 2'S) -2- (1-Acetam ido-2-h id roxi) butyl-3- (pyrazol-3-yl) -pyrrol id in-5-carboxyl ico The title compound was prepared according to the method described in Example 1K, using (±) - (2 R, 3 R, 5 R, 1) t-butyl ester 'R, 2' S) -1-f-bu toxicarbon-il-2- (1 -acetam-do-2-methoxy-methyloxy) butyl-3- (pyrazol-3-yl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-methoxymethyl-pyrrolidin-5-carboxylic acid t-butyl ester. Chromatography on silica gel with 2-propanol: acetic acid: ethyl acetate: water 1: 1: 3: 1 followed by the addition of 0.1% Trifluoroacetic acid gave the title compound (yield: 15 mg, 55%). 1H NMR (d6-DMSO) d 7.95 (d, 1H), 7.65 (br s, 1H), 6.18 (d, 1H), 4.37 (m, 1H), 4.23 (m, 1H), 4.38 (m, 1H), 4.56 (m, 1H), 2.63 (m, 1H), 2.10 (m, 1H), 1.78 (s, 3H), 1.50 ( m, 1H), 1.25 (m, 1H), 0.83 (t, J = 7.46 Hz, 3H). MS: (M-H) - = 309, (M + 35) + = 345; (M + H) + = 311, (M + Na) + = 333 Example 203 Salt of the acid tpfluoroacetic acid (±) - (2R, 3R, 5R.1'R.2'R) -2- (1-Acetamido-2-hydroxyl) but? L-3- (p? razol-3-? l) -p? rrol? d? n-5-carboxyl? co 203B t-butyl ester of the acid (±) - (2R.3R.5R.1'R.2'R) -1-f- Butoxycarboni l-2- (1 -aceta mi do-2-metox? M etiloxObuti l -3-f-but? Ld? Phen? Ls? L? Lox? Met? Lp? Rrol? D? N-5-carboxyl? Co The title compounds were prepared according to the method described in Example 202B using acid t-butyl ester (±) - (2R, 3, 5R, 1'R, 2'R) -1-f-butox? Carbon? L-2- (1-acetamido-2-hydrox?) But? L-3-f-but? ld? phen? l? l? lox? met? lp? rrol? d? n-5-carboxyl? co instead of t-butyl ester of acid (±) - (2R, 3R, 5R, 1'R, 2'S ) -1-f-butoxy carbon? L-2- (1-acetamido-2-hydrox?) But? L-3-f-but? Ld? F in ilsihloxi-met? Lp? Rrol? D ? n-5-carboxylic (yield 0217 g, 96%) 1H NMR (d6-DMSO) 674-765 (m, 10H), 470 (s, 1H), 462 (s, 1H), 435- 455 (m, 2H), 375-395 (m, 2H), 368 (m, 1H), 355 (m, 1H), 325 (m, 1H), 324 (s, 3H), 255 (m, 1H) , 245 (, 1H), 20 (m, 1H), 185 (s, 3H), 128-14 (m, 18H), 099 (d, 9H), 08 (dt, 3H) MS (MH) - = 755 , (M + 35) + = 791, (M + H) + = 757, (M + Na) + = 779 203C t-butyl ester of the acid (± - (2R.3R.5R.1 'R.2'R) -1-f- Toxic Bu rbonyl-2- (1-a-cepido-2-methoxymethyloxy) butyl-3 -hydroxy-i-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 123G using (±) - (2R, 3R, 5R, 1) t-butyl ester 'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxymethyloxy) butyl-3-f-butyldiphenylsilyloxymethyl-pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -1-f-10-butocarbonyl-l-2-oxiranyl-3-f-butylifenyl if l-loxymethyl-pyrrolidine-5-carboxylic acid (yield : 0.124 g, 83%) 1 H NMR (d 6 -DMSO) d 7.42 (dd, 1 H), 4.62-4.8 (m, 3 H), 4.48 (m, 1 H), 3. 6-3.85 (m, 3H), 3.35-3.6 (m, 4H), 3.25 (s, 3H), 2.25 (m, 1H), 2.4 (m, 1H), 2.28 (m, 1H), 1.82 (s, 3H), 1.58 (m, 3H), 1.32-1.45 (m, 15 18H), 0.9 (dt, 3H). MS: (M-H) - = 517, (M + 35) + = 553; (M + H) + = 519, (M + Na) * = 541 203D acid t-butyl ester (±) - (2R.3R, 5R.1'R.2'R) -1-r- Butoxycarbonyl-2- (1-acetamido-2-methoxymethyloxy) butyl-3-ph The title compound was prepared according to the method described in Example 123H using (±) - (2R, 3R, 5R, 1'R) t-butyl ester. , 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid in place of (±) - (-) - t-butyl ester 2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2-oxiranyl-3-hydroxymethyl-pyrroline-5-carboxylic acid (yield: 0.106 g, 86%). H NMR (d6-DMSO) 09.58 (d, 1H), 7.58 (dd, 1H), 4.6-4.72 (m, 3H), 4. 48 (d, 1H), 3.88 (d, 1H), 3.4-3.65 (, 5H), 3.24 (s, 3H), 3.15 (dd, 1H), 2.20-2.48 (m, 4H), 1.86 (s, 3H) ), 1.58 (m, 3H), 1.30-1.40 (m, 18H), 0.86 (t, 3H). MS: (M-H) - = 515, (M + 35) + = 551; (M + H) + = 517 203E t-butyl ester of (±) - (2R.3R.5R, 1'R.2'R.rRS) -1-f- B or toxicarbonyl-2- (1-acetamid o-2-methoxymethyloxy) butyl-3- (1-hydroxy-2-propyn-1-yl) -pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 38A using acid t-butyl ester ( ±) - (2R, 3R, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3-formyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1 'S, 1"RS) -1-f-butoxycarbonyl l-2- (1-acetamido-3-methyl) butyl acid t-butyl ester -3-formyl-pyrroline-5-carboxylic acid (yield: 32 mg, 76%) MS: (MH) - = 541, (M + 35) + = 577; (M + H) + = 543, (M + Na) * = 565 203F t-butyl ester of (±) - (2R.3R.5R.1'R.2'R) -1-f- Butoxycarbonyl-2- (1-acetamid o-2-methoxymethyloxy) butyl I- 3-M -oxo-2-propin-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 38B using (±) - (t) -butyl ester ( 2R, 3R, 5R, 1'R, 2'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3- (1-hydroxy-2-propyn-1-yl) ) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S, 1"RS) -1-f-butoxycarbonyl-2- (1-acetamido-3) t-butyl ester -methyl) butyl-3- (1-oxo-2-propin-1-yl) -pyrrolidine-5-carboxylic acid (yield: 25 mg, 78%). 1H NMR (d6-DMSO) d 7.49 (br d, 1H ), 5.0 (d, 1H), 4.7 (br s, 1H), 4. 55-4.7 (m, 3H) 3.88 (br d, 1H), 3.5-3.7 (m, 2H), 3.43 (t, 2H), 3.2-3.4 (m, 2H), 3.24 (s, 3H), 2.4- 2.7 (m, 2H), 1.84 (s, 3H), 1.5-1.7 (m, 2H), 1.30-1.45 (m, 18H), 0.86 (dt, 3H). MS: (M-H) - = 539, (M + 35) + = 575; (M + H) + = 541, (M + Na) * = 563 203G t-butyl ester of the acid (±) - (2R.3R.5R.1'R, 2'R) -1-f- Bu toxic rbonyl-2- (1-acetamido-2-methoxymethyloxy) butyl-3- (pi Izo-3-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 38C using (±) - (2 R, 3 R) t-butyl ester , 5R, 1'R, 2'R) -1-f-bu toxic rboni l-2- (1 -acetamido-2-methoxy-methyloxy) butyl-3- (1-oxo-2-propin-1-yl) ) -pyrrolidin-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -1-f-butoxycarbonyl-2- (1-acetamido-3-methyl) bu ti l-3- (1-oxo-2-propin-1-yl) -pi rrol id in-5-carboxylic (yield: 18 mg, 72%). 1H NMR (d6-DMSO) d 7.57 (m, 2H), 6.1 (d, 1H), 4.40-4.7 (m, 4H) 3.93 (m, 1H), 3.4-3.6 (m, 3H), 3.3-3.4 (m, 3H), 3.22 (d, 3H), 2.55-2.65 (m, 1H), 2.2 (m, 1H), 1.85 (s) , 3H), 1.5-1 7 (m, 2H), 1.15-1.45 (m, 18H), 0.86 (m, 3H). MS: (M-H) - = 553, (M + 35) + = 589; (M + H) + = 553, (M + Na) * = 577 203H salt of the acid trifluoroacetic acid (±) - (2R, 3R, 5R, 1'R, 2'R) -2- (-Acetam id o-2-hid roxi) buti l-3- (pyrazole-3- il) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 15B, using (+) - (2 R, 3 R, 5 R, 1 't-butyl ester) R, 2'R) -1-f-butocarbonyl-2- (1-acetamido-2-methoxy-methyloxy) butyl-3- (pyrazol-3-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (+) - (2R, 3R, 5R, 1'S) -1-benzyl-2- (1-acetamido-3-ethyl) pentyl-3- (imidazol-2-yl) -pyrrolidin-5 acid -carboxylic Chromatography on silica gel with 2-propanol: acetic acid: ethyl acetate: water 1: 1: 3: 1 followed by the addition of 0.1% trifluoroacetic acid gave the title compound (yield: 4 mg, 45%) . 1 H NMR (d 6 -DMSO) d 7.65 (d, 1 H), 764 (d, 1 H), 6.16 (d, 1 H), 4.37 (m, 1 H), 4.23 (m, 1 H), 4.38 (m, 1 H) ), 456 (m, 1H), 2.63 (m, 1H), 2.10 (, 1H), 1.74 (s, 3H), 1.25-1.40 (m, 2H), 0.83 (t, J = 7.46 Hz, 3H). MS: (M-H) - = 309, (M + 35) + = 345; (M + H) + = 311, (M + Na) * = 333 Example 204 (±) - (2R, 3R, 5R) -2-Acetam? Domethyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid hydrochloride. 204A (±) - (2R, 3R, 5R) -1-Benzyl-2-aminomethyl-3-f-butyldimethylsilyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester The title compound is prepared according to the method is described in Example 1F, using (±) - (2R, 3R, 5R) -1-benzyl-2-formyl-3-f-butyldimethylsilyloxylmethyl-pyrrolidone-t-butyl ester. 5-carboxylic acid instead of (±) - (2R, 3R, 5R) -1-benzyl-2- (1-oxo-3-e ti I) penyl-3-t-butyl acid t-butyl ester imeti Isi liloxy meti l-pirrolidi n-5-carboxylic acid. MS: (M + H) * = 435 204B (±) - (2R.3R.5R) -1-Benzyl-2-acetamidomethyl-3-f-butyl acid t-butyl ester Id imeti lysilyloxymethyl-pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 1G, using (±) - (2R, 3R, 5R) -1-benzyl-2-aminomethyl-3-t-butyl ester. f-butyl? metilsililox? metli- pyrrolidine-5-carboxylic acid in place of (+) - (2R, 3R, 5R, 1'R) - and (±) - (2R, 3R, 5R, 1 'S) -1 t-butyl ester -benzyl-2- (1-amino-3-et? l) pentyl-3-t-butyldimethylsilyloxymethyl-pyrrolidine-5-carboxylic acid. 1H NMR (CDCU): d 7.2-7.35 (m, 5H), 6.14 (br, 1H), 3.86 (dd, J = 18Hz, 13.5Hz, 2H), 3.67 (m, 1H), 3.60 (m, 1H) , 3.49 (m, 1H), 3.28 (m, 1H), 3.06 (m, 1H), 2.19 (m, 2H), 1.95 (s, 3H), 1.45 (s, 9H), 0.91 (s, 9H), 0.07 (s, 6H). MS: (M + H) * = 477 204C (±) - (2R.3R, 5R) -1-Benzyl-2-acetamidomethyl-3-hydroxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester The title compound was prepared according to the method described in Example 1H, using (±) - (2R, 3R, 5R) -1-benzyl-2-acetamidomethyl-3-f-butyldimethylsilyloxymethyl-pyrrolidine-5-carboxylic acid t-butyl ester instead of t-butyl ester of (±) - (2R, 3R, 5 R, 1'S) - 1 -benzyl-2- (1 -acetamido-3-ethyl) penthyl-3-f-butyl-ethylsilyloxymethyl-pyrrolidine-5-carboxylic acid .

O J AcNH_ 7 \ OtBu H? ? fko Ph 204D t-butyl ester of (±) - (2R.3R.5R) -1-Benzyl-2-acetamido-meth? l-3-formyl-pi rrol idin-5-carboxyl ico The title compound was prepared according to the method described in Example 2A, using acid t-butyl ester (+) - (2R, 3R, 5R) -1-benzyl-2-acetamidomethyl-3-hydroxymethyl-pyrrolidin-5-carboxylic acid instead of t-butyl ester of (+) - (2R, 3R, 5R, 1'S ) -1- benzyl-2- (1-acetamido-3-ethyl) pentyl-3-hydroxymethyl-pyrrolidin-5'-carboxylic acid. ? NMR (CDCU): d 9.70 (s, 1H), 7.22-7.36 (m 5H), 5.82 (br, 1H), 3.83 (dd, J = 3.3Hz, 13.5Hz, 2H), 3.74 (m, 1H), 3.56 (d, J = 9Hz, 1H), 3.15 (m, 1H), 2.73 (m, 1H), 2 36-2.10 (m, 2H), 1.98 (s, 3H), 1.45 (s, 9H).

MS: (M + H) * = 361 204E (±) - (2R.3R.5R) -1-Benzyl-2-acetamido-methyl-3-me t-butyl ester rbonyl-pyrrolidin-5-carboxylic acid t-butyl ester The title compound was prepared in accordance with method described in Example 2B and 2C, using (±) - (2R, 3R, 5R) -1-benzyl-2-acetamidomethyl-3-formyl-pyrrolidin-5-butyl ester carboxylic acid instead of t-butyl ester of (±) - (2R, 3R, 5R, 1 'Si-i-be nc? l-2- (1 -acetamido-3-ethyl) pen ti l-3-f ormylpyrrolid i n-5-carboxylic acid 1 H NMR (CDCU): d 7.45-7.20 (m, 5H), 5.96 (br, 1H), 3.90-3.73 (m, 4H), 3.71 (s, 3H) , 3.52 (dd, J = 9Hz, 2Hz, 1H), 3.13 (m, 1H), 2.84 (m, 1H), 2.36 (m, 1H), 2.18 (m, 1H), 1.97 (s, 3H), 1.45 (s, 9H) MS: (M + H) * = 391 204F (+) - (2R.3R, 5R) -2-Acetamidomethyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid t-butyl ester The title compound was prepared according to the method described in Example 2D , using (±) - (2R, 3R, 5R) -1-benzyl-2-acetamidomethyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid t-butyl ester in place of the acid t-butyl ester ( ±) - (2R, 3R, 5R, 1'S) -1-be ncyl-2- (1 -acetamido-3-ethyl) pen ti I- 3- e toxi carbon il-pyrrole-n-5-carboxylic acid. • H NMR (CDCU): 56.19 (br, 1H), 3.72 (m, 2H), 3.70 (s, 3H), 3.43 (m, 1H), 3.28 (m, 1H), 2.74 (m, 1H), 2.44 (m 1H), 2.21 (m, 1H), 2.00 (s, 3H), 1.48 (s, 9H). MS: (M + H) * = 301 HCl 204G (±) - (2R, 3R, 5R) -2-Acetamidomethyl-3-methoxycarbonyl-pyrrolidine-5-carboxylic acid hydrochloride. The title compound was prepared according to the method described in Example 2E using (±) - (2R, 3R, 5R) -2-acetamidomethyl-3-methoxycarbonyl-pyrrolidin-5-butyl ester. -carboxylic acid instead of t-butyl ester of (±) - (2R, 3R, 5R, 1'S) -2- (1-a-tamido-3-ethyl) pentyl-3-methyl rbonyl-? irrolidin-5 - carboxyl. 1H NMR (D20): d 4.42 (t, J = 8.25Hz, 1H), 4.22 (m, 1H), 3.83 (, 1H), 3.75 (s, 3H), 3.70-3.60 (m, 2H), 3.26 ( m, 1H), 2.78 (m, 1H), 2.43 (, 1H), 2.03 (s, 3H). MS: (M + H) * = 245 Examples 205-213 The following compounds were prepared according to the methods described in Examples 1-39 from the common intermediate prepared as described in Example 204C.

Example 205 TFA Salt of trifluoroacetic acid of (±) - (2R.3R.5R) -2-Acetamidomethyl-3-ethoxycarbonyl-pyrrolidine-5-carboxylic acid. 1H NMR (D20) d 4.30 (t, J = 8.2Hz, 1H), 4.21 (m, 3H), 3.62 (dd, J = 2.4, 3.4Hz, 2H), 3.23 (m, 1H), 2.74 (m, 1H), 2.38 (m, 1H), 2.02 (s, 3H), 1.26 (m, 3H) MS: (M + H) * = 259; (M-H) '= 257.

Example 206 < ^ N AcHN ^? / ° H HCl Acid hydrochloride (±) - (2R.3R.5R) -2-Acetamidomethyl-3- (imidazol-2-yl) -pyrrolidin-5-carboxylic acid 1H NMR (D20): d 7.46 (s, 2H), 4.53 (dd, J = 9.5Hz, J = 8.5 Hz, 1H), 4.28 (m, 1H), 3.96 (m, 1H), 3.65 (m, 2H), 3.03 (dt, J = 13.5Hz, J = 7.6Hz, 1H), 2.46 (m, 1H), 1.94 (s, 3H). MS: (M + H) * = 253, (M-H) = 251 Example 207 A < = HN ^} OH HH í TFA Salt of trifluoroacetic acid of (±) - (2R.3S.5R) -2- Acetamidomethyl-3-vinyl-pyrrolidin-5-carboxylic acid. 1H NMR (D20) d 5.74 (m, 1H), 5.24 (m, 2H), 4.20 (dd, J = 1.7, 8.1Hz, 1H), 3.65 (m, 2H), 3.50 (m, 1H), 2.84 (m, 1H), 2.61 (m, 1H), 2.03 (s, 3H), 1.95 (m, 1H) MS: (M + H) * = 213.

Example 208 Salt of the acid trifluoroacetic acid (±) - (2R.3R.5R) -2-Acetamidomethyl-3- (2, 2-dimethyl-1-vinyl) -pyridin-5-carboxylic acid. 1H NMR (D20) 65.01 (br d, 1H), 4.18 (dd, J = 2.1, 8.1Hz, 1H), 3.53 (m, 3H), 3.04 (m, 1H), 2.55 (m, 1H), 2.0 (s, 3H), 1.75 (m, 1H), 1.72 (s, 3H), 1.67 (s, 3H) MS: (M + H) * = 241, (M + Na) * = 263; (M-H) - = 239.

A-y-zy-yO.

Example 209 HCl Salt of trifluoroacetic acid of (±) - (2R.3R.5R) -2-Acetami-omethyl-3- (N, N-dimethylcarbamoyl) -pyridine-5-carboxylic acid. 1H NMR (D20) 6 4.60 (t, J = 8.4Hz, 1H), 4.23 (m, 1H), 3.56 (d, J = 5.8Hz, 2H) 3.50 (m, 1H), 3.10 (s, 3H), 2.94 (s, 3H), 2.88 (m, 1H), 2. 19 (m, 1H), 2.00 (s, 3H) MS: (M + H) * = 258, (M-H) - = 256.

Example 210 H3C or m-y AcHN? H H 0 TFA Salt of trifluoroacetic acid of (±) - (2R, 3R.5R) -2-Acetamidom eti l-3- (N-methylcarbamoyl) -pyrrolidine-5-carboxylic acid. 1H NMR (D20) 4.49 (t, J = 8.5Hz, 1H), 4.10 (m, 1H), 3.57 (d, J = 5.8Hz, 2H), 3.03 (m, 1H), 2.76 (m, 1H), 2.74 (s, 3H), 2.29 (m, 1H), 2.00 (s, 3H) MS: (M + H) * = 244.

Example 211 H3C Salt of (+) - (2R.3R.5R) -2- Acetamidomethyl-3-propionyl-pyrrolidine-5-carboxylic acid trifluoroacetic acid. H NMR (D20) d 4.24 (m, 2H), 3.55 (d, J = 4.7Hz, 1H), 3.40 (m, 1H), 2. 85 (m, 1H), 2.64 (m, 3H), 2.16 (m, 1H), 2.01 (s, 3H), 1.02 (t, J = 7.1Hz, 3H) MS: (M + H) * = 243; (M-H) '= 241 Example 212 Acid chlorohydrate (±) - (2R.3R, 5R) -2-Acetamidomethyl-3-methoxymethyl-pyrrole-n-5-caboxic acid H NMR (D20): d 4.44 (t, J = 6Hz, 2H) , 3.77 (np, 1H), 3.65-3.48 (m, 3H), 3.35 (s, 3H), 2.64 (m, 1H), 2.56 (, 1H), 2.03 (s, 3H), 2.00 (m, 1 HOUR). MS: (M + H) * = 231, (M-H) - = 229 Example 213 TFA Salt of trifluoroacetic acid of (±) - (2R.3S, 5R) -2- Acetamidomethyl-3-methyl-pyrrolidine-5-carboxylic acid. 'H NMR (D20) d 4.30 (m, 1H), 3.64 (m, 1H), 3.48 (m, 1H), 3.20 (m, 1H), 2.64 (m, 1H), 2.03 (s, 3H), 1.76 (m, 1H), 1.32 (br t, 1H), 1.12 (m, 4H) MS: (M + H) * = 201, (M + Na) * = 223.

Example 214 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1'R) -2- (1-Acetamido-2-ethylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid BocHN. - L ^ XX .Cfeu "-S- ° 214A t-butyl ester of (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1-f-butoxycarbonylamino) non-2-ethylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid.

To a solution of ethanethiol (0.047 mL, 0.63 mmol) in THF (2 mL) at 0 ° C was added 2.5 M. n-BuLi / hexane (0.248 mL, 0.62 mmol). The reaction mixture was stirred for 45 minutes and a solution of t-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-f-butoxycarbonyl-2- (N-f-) butoxycarbonylaziridinyl) -3-vinyl-pyrrolidin-5-carboxylic acid (0.08 g, 0.182 mmol) in THF (0.5 mL) was added followed by DMF (1.5 mL) and stirred at room temperature for 2 hours. hours. The reaction was forged with 1N. NaHCO3 (10 mL) and diluted with ethyl acetate (20 mL). The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give the title compound (yield '61 mg, 67%). 1H NMR (d6-DMSO) 5 6.74 (br d, 1H), 5.85 (, 1H), 4.9-5.0 (m, 2H), 4.20 (m, 1H), 3.95 (m, 1H), 3.75 (d, 1H), 2.8-3.0 (dd, 1H), 2.5 (m, 3H), 1.65 (m, 1H), 1.32-1.45 (m , 27H), 1.17 (dt, 3H). MS: (M-H) - = 499; (M + H) + = 501, (M + Na) * = 523 214B (±) - (2R, 3S, 5R, 1 'R) -1-f-Butoxycarbonyl-2- (1-Nf-butoxycarbonylacetamido-2-ethylthio) ethyl-3-vinyl t-butyl ester -? irrolidin-5-carboxylic. (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1-N-butoxycarbonylamino-2-thylthio) ethyl-3-vinyl- t-butyl ester pyrrolidin-5-carboxylic acid (58 mg, 0.116 mmol) was reacted with lithium hexamethyldisilazide (1 M) (1 16 mL, 1.16 mmol) in THF (3 mL) at -78 ° C. After 0.5 hour at -78 ° C and 1 hour at -40 ° C, the above reaction mixture was reacted with acetyl chloride (0.166 mL, 2.33 mmol) at -0 ° C for O 3 hours. The reaction was set with 1N NaHCO3 (10 L) and extracted with ethyl acetate (20 mL). The organic layer was washed with water, and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel using 10% ethyl acetate / hexanes to give the title compound (yield: 28 mg, 44%). 1 H NMR (d 6 -DMSO) 5 5.88 (m, 1 H), 4.9-5.0 (m, 2 H), 4.52 (m, 1 H), 4. 33 (, 1H), 4.1 (m, 1H), 2.78 (dd, 1H), 2.3-2.5 (m, 6H), 1.7 (m, 1H), 1.32-1.5 (m, 27H), 1.11 (t, 3H) ). MS: (M + H) + = 543. 214C salt of (+) - (2R.3R.5R.1'R) -2- (1-Acetamido-2-ethylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid trifluoroacetic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2 R, 3S, 5 R, 1'R) -1-f-butoxy carbo nil-2- (t) butyl ester ( 1-Nf-bu toxicity rbon il-acetamido-2-ethylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2R, 3S, 5R, 1 ' R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 7 mg , 95%). 1 H NMR (d 6 -DMSO) 5 8.15 (d, 1 H), 5.72 (m, 1 H), 5.05-5.2 (m, 2 H), 42-4.4 (m, 2H), 4.33 (m, 1H), 2.93 (m, 1H), 2.7-2.8 (2d, 1H), 2.3- 2.6 (m, 3H), 1.85-1.95 (m, 1H), 1.93 (s, 3H), 1.17 (t, J = 7.46 Hz, 3H) MS: (M + H) + = 287.

Example 215 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R.3'S) -2- (1-Acetamido-2-ethylsulfinyl) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 215A t-butyl ester of acid (±) - (2R.3S.5R.1 'R.3'S) and (±) - (2R.3S.5R. 1'R.3'R) -1-f- Bu toxica rbonyl-2- (1-Nf-bu toxic rbonila ceta mido-2-etilsulfiniUe ti l-3-vinyl-pyrrolidin-5-carboxylic acid) Reacted t-butyl ester of acid (±) - (2R, 3S , 5R, 1'R) -1- f- Butoxycarbon I-2- (1-Nf-bu toxycarbon I acetamide-2-ethylthio) eti I-3- 15 vinyl-pyrrolidine-5-carboxylic acid ( 72 mg, 0.132 mmol) with 55% m-chloroperoxybenzoic acid (41 mg, 0.132 mmol) in CHCl3 (1.5 mL) at -40 ° C for 30 minutes The reaction was concentrated in vacuo, the residue was purified by chromatography on silica gel using ethyl acetate to give the isomer of the title compounds (±) - 20 (2R, 3S, 5R, 1'R, 3'S) (yield: 14 mg, 18.9%) and (±) - (2R , 3S, 5R, 1'R, 3'R) (yield: 45 mg, 60.7%). (2R, 3S, 5R, 1'R, 3'S) 1H NMR (d6-DMSO) d 5.88 (m, 1H) , 4.9-50 (, 2H), 4.50 (m, 1H), 4.0-4.15 (, 1H), 2.7-2.9 (m, 3H), 255 (m, 1H), 237 (s, 3H), 1 7 (m, 1H), 1 32-1 5 (m, 27H), 1 12 (t, 3H) MS (M + H) + = 559, (M + Na) + = 581 (2R, 3S, 5R, 1'R, 3'R) 1 H NMR (d6-DMSO) d 588 (m, 1H), 49-50 (m, 2H), 450 (m, 1H), 403-415 (m, 1H), 32 (m, 1H) 31 (dd, 1H), 25-27 (m, 2H), 238 (s, 3H), 1 75 (m, 1H), 1 32-1 5 (m, 27H), 1 12 (t, 3H) MS (M + H) + = 559, (M + Na) + = 581 215B salt of the acid tpfluoroacetic acid (±) - (2R, 3S.5R, 1'R, 3'S) -2- (1-Acetamido-2-et? Lsulf? N? L) et? L-3 - v? n? -? rrol? d? n-5-carboxyl? co The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 3'S) -1-f-butox? Carbon? L-2- (1-Nf-butox? Carbon? L-15 acetam? Do-2-et? Lsulf? N? l) et? l-3-v? n? lp? rrol? d? n-5-carboxyl? co instead of acid t-butyl ester (±) - (2R, 3S, 5R, 1'R, 2'S ) -1-f-butox? Carbon? L-2- (1- acetamido-2-hydrox?) But? L-3- (c / s-propen-1-? L) -pyrol ? d? n-5-carbox? l? co Ester (yield 9 mg, 86%) H NMR (d6-DMSO) 5 839 (d, 1H), 572 (m, 1H), 515-52 (dd, 2H ), 45 (m, 1H), 437 (m, 1H), 365 (m, 1H), 285-304 (m, 3H), 26-285 (m, 2H), 24 (m, 1H) 1 83-1 95 (m, 1H), 1 86 (s, 3H), 1 20 (t, J = 746 Hz, 3H) MS: (M-H) - = 301; (M + H) + = 303, (M + Na) * = 325 Example 216 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.3'R) -2- (1-Acetamido-2-ethylsulfinyl) ethyl-3-v? Nyl-pyrrolidin-5 -carboxylic The title compound was prepared according to the method described in Example 41C, using t-butyl ester of (+) - (2R, 3S, 5R, 1'R, 3'R) -1-f- butoxycarbonyl-2- (1-N-butoxycarbonyl-acetamido-2-ethylsulfinyl) ethyl-3-vinyl-? irolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1) t-butyl ester 'R, 2'S) -1-f-butoxycarbonyl 2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 12 mg, 94 %). H NMR (d6-DMSO) 6 8.39 (d, 1H), 572 (m, 1H), 5.15-5.2 (dd, 2H), 453 (m, 1H), 4.41 (t, 1H), 3.65 (m, 1H), 3.2 (dd, 1H), 2.9-3.0 (m, 2H), 2.65-2.9 (m, 2H), 2.4 (m, 1H), 1.83-1.95 (m, 1H), 1.83 (s, 3H), 1.20 (t, J = 7.46 Hz, 3H) MS: (MH) - = 301; (M + H) + = 303, (M + Na) + = 325 Example 217 Salt of the acid tpfluoroacetic acid (±) - (2R.3S.5R, 1'R) -2- (1-Nfb or toxic rbo n Maceta m? Do-2-et? Lsulf on? L) et? l-3-v? n il-pi rrol id i n-5-carboxyl 217At-butyl ester of the acid (+) - (2R.3S, 5R, 1'R) -1-f-Butox? Carbon? L-2- (1-Nf-butox? Carbon? Lacetam? Do-2) -et? lsulfon? l) et? l-3-v? n? lp? rrol? d? n-5-carboxihco It was reacted t-butyl ester of acid (±) - (2R, 3S, 5R, 1 ' R, 3'R) -1-f-Butox? Carbon? L-2- (1-Nf-butox? Carbon? L-acetam? Do-2-et? Lsulf? N? L) et? L-3- v? n? lp? rrol? d? n-5-carbox? l? co (25 mg, 00448 mmol) with 55% m-chloroperoxybenzoic acid (14 mg 00448 mmol) in CHCU (1 5 mL) at 0 ° C for one hour The reaction was concentrated in vacuo. The residue was purified by chromatography on silica gel using 25% ethyl acetate / hexane to give the title compound (yield 237 mg, 92%) 1H NMR (d6-DMSO). 588 (, 1H) 485-50 (m, 2H), 438 (m, 1H), 415 (m, 1H), 37 (m, 1H) 345 (dd, 1H), 29-32 (m, 3H), 25-27 (m, 1H), 23-24 (m, 3H), 1 6- 204 (m, 1H), 1 35-1 55 (m, 27H), 1 15 (t 3H) MS (M + H) + = 575 217B salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1 'R) -2- (1-Acetarpido-2-ethylsulfonyl) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2-t (butyl ester) ( 1-N-butoxycarbonyl-acetamido-2-ethylsulfonyl) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester - 1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-pro? En-1-yl) -pyrrolidine-5-carboxylic acid (yield: 12 mg, 94% ). 1H NMR (d6-DMSO) 6 8.34 (d, 1H), 5.72 (m, 1H), 5.05-5.25 (dd, 2H), 4. 68 (m, 1H), 4.39 (dd, 1H), 3.7 (2d, 1H), 3.48 (dd, 1H), 3.3-3.4 (dd, 2H), 3.08 (q, 2H), 2.95 (m, 1H) , 2.42 (m, 1H), 1.9 (m, 1H), 1.84 (s, 3H), 1.23 (t, J = 7.46 Hz, 3H). MS: (M-H) '= 317, (M + 35) + = 353; (M + H) + = 319, (M + Na) * = 341 Examples 218-220 The following compounds were prepared in 3 steps of fc. ? b •• according to the methods described in Example 214 Example 218 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R) -2- (1-Acetamido-2-isopropylthio) ethyl-3-vinyl-pyrrole-n-5-carboxylic acid BocHN. 7 ^ V O'Bu and I- μ HNBOC Y0 S 218A t-butyl ester of (±) - (2R.3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1-Nf) -butoxycarbonylamino-2-isopropylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 214A, but using isopropylthiol in place of ethanethiol (yield: 22 mg, 62%). H NMR (d6-DMSO) 6 6.73 (d, 1H), 5.85 (m, 1H), 4 9-5.0 (m, 2H), 4.18 (m, 1H), 3.95 (m, 1H), 3.75 (br d , 1H), 2.8-3.0 (m, 2H), 1.65 (m, 1H), 1.32-1.45 (m, 27H), 1.18 (dd, 6H) MS: (MH) - = 513; (M + H) + = 515, (M + Na) + = 537 218B (±) - (2R.3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1- (N-butoxycarbonyl-N-acetamido) -2-isopropylthio) t-butyl ester ethyl-3-vinyl-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 214B, using (+) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2-t-butyl ester (1-N-butoxycarbonylamino-2-isoproylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid in place of (+) - (2R, 3S, 5R, 1'R) -1-r-t-butyl ester -Butoxycarbonyl-2- (1-N-butoxy-carbonylamino-2-y thiyl) eti I- 3-vin i I-pyrro lidin-5-carboxylic acid (yield: 12 mg, 50%). 1 H NMR (d 6 -DMSO) 5 5.86 (m, 1 H), 4.88-5.0 (m, 2 H), 4.54 (m, 1 H), 4.33 (, 1 H), 4.13 (d, 1 H), 3.05 (m, 1 H) , 2.73-2.84 (m, 2H), 2.38 (br s, 3H), 1.72 (m, 1H), 1 32-1.5 (m, 27H), 1.14 (dd, 6H). MS: (M + H) + = 557, (M + Na) + = 579 TFA 218C salt of the acid trifluoroacetic acid (+.) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-isopropylthi or) ethyl-3-vinyl-pyrrolidin-5-carboxylic acid The title compound was prepared according to the method described in Example 15B. using t-butyl ester of acid (+) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-N-butoxycarbonyl-acetamido-2-isopropylthio) etl-3-vinyl-pyrrolidone -5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy) t-butyl ester ) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 8 mg, 97%). H NMR (d6-DMSO) d 8.14 (d, 1H) ,. 5.72 (m, 1H), 5.05-5.2 (dd, 2H), 4.2-4.4 (m, 2H), 3.68 (dd, 1H), 2.93 (m, 2H), 2.74 (dd, 1H), 2.58 (dd, 1H), 1.93 (m, 1H), 1.87 (s, 3H), 1.2 (t, 6H) MS: (MH) - = 299; (M + H) + = 301, (M + Na) + = 323 Example 219 (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-phenylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride 219A (±) - (2R.3S.5R.1'R) -1-f-Butoxycarbonyl-2- (1-amino-2-phenylthio) ethyl-3-vinyl-pyrrolidin-5-butyl ester carboxylic T-butyl ester of (±) - (2R, 3S, 5R, 1'S) -1-t-Bu, rbonyl-2-aziridinyl-3-vinyl-pyrrolidine-5-carboxylic acid (20.3 mg, 0.06 mmol) was reacted ) with phenylthiol (19.9 mg, 0.18 mmol) and triethylamine (0.047 mL, 034 mmol) in MeOH (0.06 mL) at room temperature for 3.5 hours. The reaction solution was concentrated in vacuo. The residue is chromatographed on a preparative thin layer on silica gel using ethyl acetate / methanol / ammonium hydroxide, 99/0 05 / 0.05, to give the title compound (yield 20.7 mg, 77%). 1 H NMR (d 6 -DMSO) d 7.31 (m, 4 H), 7 17 (m, 1 H), 5.87 (m, 1 H), 5.03 (d, J = 17 Hz, 0.4 H), 5.01 (d, J = 17 Hz, 0.6H), 4.91 (d, J = 11H, 0.4H), 4.90 (d, J = 11Hz, 0.6H), 4.15 (m, 1H), 3.82 (, 0.6H), 3.76 (m, 0.4H), 3.39 (m, 1H), 2.92 (m, 2H), 2.55 (m, 1H), 1.64 (m, 2H), 1.42 (s, 5.4H), 1.37 (s, 3.6H), 1.34 (s, 5.4H) ), 1.22 (s, 3.6H) MS: (M + H) * = 449, (M + Na) * = 471 219B (±) - (2R, 3S, 5R.1'R) -1-f-Butoxycarbonyl-2- (1 -acetam ido-2-f in ilthio) ethyl-3- nyl- t-butyl ester pyrrolidin-5-carboxylic acid. The (±) - (2R, 3S, 5R, 1'R) -1-t-Butoxycarbonyl-2- (1-am-ino-2-phenyl) ethyl ester was reacted. -3- saw neither I-pyrrolidine-5-carboxylic acid (17.2 mg, 0.04 mmol) with acetic anhydride (0.011 mL, 0.11 mmol) and triethylamine (0.032 mL, 0.23 mmol) in CH2Cl2 (0.3 mL) at rt during 4.25 hours The reaction solution was concentrated in vacuo. The residue is chromatographed on a preparative thin layer on silica gel using 5% methanol / dichloromethane to give the title compound. 1H NMR (de-DMSO) d 7.75 (d, J = 9Hz, 0.6H), 7.73 (d, J = 9Hz, 04H), 7.32 (m, 4H), 7.19 (m, 1H), 5.87 (m, 1H ), 5.04 (d, J = 17Hz, 0.4H), 5.00 (d, J = 17Hz, 0.6H), 4.95 (d, J = 10Hz, 0.6H), 4.93 (d, J = 10Hz, 0. 4H), 4.59 (m, 0.4H), 4.45 (m, 0.6H), 3.99 (dd, J = 10Hz, 2Hz, 0.6H), 3.94 (dd, J = 10Hz, 2.5Hz.0.4H), 3.84 ( m, 0.6H), 3.77 (m, 0.4H), 3.07 (dd, 13Hz, 5Hz, 0.6H), 2.95 (m, 1.8H), 2.83 (br t, J = 8Hz, 0.6H), 2.48 (m , 1H), 1.84 (s, 1.2H), 1.81 (s, 1.8H), 1.68 (m, 1H), 1.41 (s, 5.4H), 1.36 (s, 3.6H), 1.34 (s, 5.4H) , 1.26 (s, 3.6H) MS: (MH) '= 489, (M + 35) "; (M + H) * = 490, (M + Na) * = 513 219C (±) - (2R.3S, 5R, 1'R) -2- (1-Acetamido-2-phenylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid hydrochloride The title compound was prepared in accordance with the method described in Example 1K, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-phenylthio) t-butyl ester ) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-ethyl) pentyl-3-t-butyl ester (methoxymethyl) -pyrrolidine-5-carboxylic acid (yield: 14.6 mg, 100%.) 1H NMR (d4-methanol) 67.43 (m, 2H), 7.31 (m, 3H), 5.75 (ddd, J = 17Hz, 10Hz, 8Hz, 1H), 5.32 (brd, J = 17Hz, 1H), 5.19 (dd, J = 10Hz, 1.4Hz, 1H), 4.58 (m, 2H), 3.89 (dd, J = 10Hz, 3Hz, 1H) , 3.19 (dd, J = 14Hz, 6Hz, 1H), 3.09 (dd, J = 14Hz, 9Hz, 1H), 3.04 (m, 1H), 2.57 (dt, J = 13Hz, 7Hz, 1H), 2.04 (s) , 3H), 2.03 (m, 1H) MS: (MH) - = 333; (M + H) + = 335, (M + Na) * = 357 EXAMPLE 220 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R.1'R) -2- (1-Acetamido-2-benzylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid 220A (±) - (2R.3S, 5R, 1'R) -1-f-Butoxycarbonyl-2- (1-Nf-butoxycarbonylamino-2-benzylthio) ethyl-3-vinyl-pyrrolidinyl acid t-butyl ester 5-carboxylic acid The title compound was prepared according to the method described in Example 214A, but using benzyl mercaptan instead of ethanethiol (yield: 28 mg, 72%). 1 H NMR (d6-DMSO) 6 7.2-7.35 (m, 5H), 6.80 (br d, 1H), 5.84 (m, 1H), 4. 86-4.96 (m, 2H), 4.25 (m, 1H), 3.95 (m, 1H), 3.7-3.8 (m, 3H), 2.76-2.94 (m, 1H), 235-2.45 (m, 2H), 1.65 (, 1H), 1.32-1.45 (m, 27H) MS. (M-H) - = 561; (M + H) + = 563, (M + Na) + = 585 220B t-butyl ester of (±) - (2R.3S.5R.1'R) -1-f-Butoxycarbonyl-2- (1- (Nf-bu toxi carbon il-acetamido) -2-benzylthio) eti I-3- vi ni l-pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 214B, using (±) - (2R, 3S, 5R, 1'R) -1-f-Butoxycarbonyl-2-t-butyl ester. - (1-N-butoxycarbonylamino-2-benzylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R) -1- t-butyl ester f-Butoxycarbonyl-2- (1-N, -butoxy-10-carbonylamino-2-ethylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylate (yield: 3.3 mg, 61%). 1 H NMR (d6-DMSO) d 7.2-7.35 (m, 5H), 5.84 (m, 1H), 4.86-4.96 (m, 2H), 4.55 (m, 1H), 4.32 (d, 1H), 4.05 (d, 1H), 3.56-3.65 (m, 2H), 2.9 (m, 1H), 2.3-2.65 (m, 3H), 2.42 (s, 3H), 1.76 (d, 1H), 1.25-1.55 (m, 15 27H) MS: (M + H) + = 605, (M + Na) + = 627 twenty y.tés- .- a.,. * 220C salt of (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-benzylthio) ethyl-3-vinyl-pyrrolidine-5-carboxylic acid trifluoroacetic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-Nf-) t-butyl ester butoxycarbonyl-acetamido-2-benzylthio) ethyl-3-vinyl-pyrrolidine-5-carboxyl? co in place of (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester - 1-f-Butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -? Irolidine-5-carboxylic acid (yield - 2.2 mg, 95%) . 1H NMR (d6-DMSO) d 8.18 (d, 1H), 7.2-7.32 (m, 5H), 5.68 (m, 1H), . 02-5.2 (m, 2H), 4.3-4.45 (m, 2H), 3.76 (s, 2H), 3.68 (dd, 1H), 2.92 (m, 1H), 2.62 (dd, 1H), 2.32-2.55 ( m, 2H), 1.85-1.95 (, 1H), 1.89 (s, 3H). MS: (M-H) - = 347; (M + H) + = 349, (M + Na) * = 371 Example 221 (±) - (2R, 3S, 5R.1'R) -2- (1-Acetamido-2- (4-pyridinetio) ethyl-3-vinyl-pyrrolidin-5-ca-carboxymethyl) hydrochloride. title was prepared according to the method of Example 219A-C but using 4-thiopyridine in place of thiophenol as the reagent in Example 219A.1H NMR (d4-methanol) d 8.57 (d, J = 7Hz, 2H), 7.97 ( d, J = 7Hz, 2H), 5.85 (ddd, J = 17Hz, 10Hz, 9Hz, 1H), 540 (br d, J = 17Hz, 1H), 5.25 (dd, J = 17Hz, 10Hz, 1H), 4.67 (dt, J = 10Hz, 4Hz, 1H), 447 (dd, J = 10Hz, 8Hz, 1H), 4.01 (dd, J = 10Hz, 4Hz, 1H), 3.68 (dd, J = 14Hz, 5Hz, 1H) , 3.45 (dd, J = 14Hz, 10Hz, 1H), 3.16 (m, 1H), 2.65 (dt, J = 14Hz, 7Hz, 1H), 2.07 (m, 1H), 2.04 (s, 3H) MS: ( MH) - = 334; (M + H) * = 336, (M + Na) * = 358 Example 222 Ethyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy) butyl-3- (c / s-propen-1 -yl) - id i n-5-carboxyMool. Thionyl chloride (1.49 L, 20.5 mmol) was reacted with Ethanol (25 mL) at 0 ° C for 10 minutes. Salt of trifluoroacetic acid acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy) butyl-3- (c / s-propen-1-) il) -pyrrole din-5-carboxylic acid (815 mg, 2.05 mmol) in ethanol (50 mL) was added to the preceding solution and reacted at room temperature for 17 hours. The reaction was concentrated in vacuo and the residue was purified by chromatography on silica gel with 90/10 / 0.5 dichloromethane / methanol / ammonium hydroxide to give the title compound as a white solid (yield: 462 mg, 72%) . 'H NMR (DMSO-dβ) d 7.49 (d, J - 9.8 Hz, 1H), 5.31 (m, 2H) 4.11 (m, 2H), 3.72 (t, J = 7.7 Hz, 1H), 3.69 (m, 1H), 3.42 (m, 1H), 3.07 (, 1H), 2.85 (m, 1H), 2.22 (m, 1H), 1.76 (s, 3H), 1.54 (d, J = 5.6 Hz, 3H), 1.45 (m, 1H), 1.39 (, 1H), 1.21 (m, 1H), 1.19 (t, J = 7.0 Hz, 3H), 0.83 (t, J = 7.3 Hz, 3H). MS: (M + H) * = 313, (M + Na) * = 335, (M-H) - = 311.

Example 223 Ethyl ester of (+) - (2R, 3R, 5R.1'R, 2'S) -2- (1-Acetamido-2-hydroxy) butyl-3- (pyrazol-3-yl) -pyrrolidone-5 -carboxylic The title compound is prepared according to the method which is described in Example 222, using trifluoroacetic acid salt of (±) - (2R, 3R, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy) butyl-3- (pyrazole) -3-yl) -pyrrolidine-5-carboxylic acid instead of the trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamide-2-hydroxy) butyl-3- (c / s-pro pen- 1 -i I) - pyrrolidine-5-caboxylic acid (yield: 32 mg, 52%). 1 H NMR (d 6 -DMSO) 5 7.6 (br s, 1 H), 6.1 (br s, 1 H), 4.08 (q, J = 7.12 Hz, 2 H), 3.78 (m, 1 H), 3.65 (m, 1 H), 3.55 (m, 1H), 3.45 (m, 1H), 3.25 (m, 1H), 3.45 (m, 1H), 1.72 (s, 3H), 1.45 (m, 1H), 1.2 (m, 1H), 1.16 (t, J = 7.12 Hz, 3H), 082 (t, J = 7.46 Hz, 3H). MS: (M-H) - = 337, (M + 35) + = 373; (M + H) + = 339, (M + Na) * = 361 Example 224 Ethyl ester of (±) - (2R.3S.5R.1'S.3'S) -2- (1-Acetamido-2- (N-isopropyl-N-methylamino-N-oxide)) ethyl-3- ( c / s-propen-1-yl) -? -rololidin-5-carboxylic acid The title compound is prepared according to the method described in Example 222, using trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-isopropyl) -N-methylamino-N-oxide)) et? L-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxyl? co instead of the trifluoroacetic acid salt of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 25 mg, 34%). 1H NMR (MeOD-d3) d 5.51-5.43 (m, 1H), 5.34-5.27 (m, 1H), 4.36-4.30 (m, 1H), 4.18 (q, J = 7.1Hz, 2H), 3.88 (dd) , J = 6.8, 8.8Hz, 1H), 3.82-3.67 (m, 2H), 3.49-3.42 (m, 1H), 3.34 (s, 3H), 3.14-2.96 (m, 1H), 2.42-2.33 (m , 1H), 1.92 (s, 3H), 1.64-1.52 (m, 1H), 1.63 (dd, J = 1.7, 6.8Hz, 3H), 1.41-1.24 (m, 1H), 1.39 (d, J = 6.4 Hz, 3H), 1.31 (d, J = 6.4Hz, 3H), 1.26 (t, J = 7.1Hz, 3H). MS: (M + H) * = 356, (M + Na) * = 378, (M-H) = 354, (M + 35) * = 390.

Example 225 Ethyl ester of (+) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3- (c / s-pr? Pen-1-yl) -pi rrol idi n-5-caboxylic acid The title compound is prepared according to the method described in Example 222, using the trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in place of the trifluoroacetic acid salt of (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy) butyl-3- (c / s-propen-1-M) -pyrrolidin-5-ca-carboxylic acid (yield: 838 mg, 94%). 1H NMR (CDCU): d 5.50 (m, 1H), 5.41 (m, 1H), 5.28 (m, 1H), 4.21 (q, J = 75Hz, 2H), 406 (m, 1H), 387 (t, J = 75Hz, 1H), 3 10 (m, 1H), 297 (m, 1H), 2.39 (m, 1H), 1.97 (s) , 3H), 1.66 (dd, 3H), 1.60 (m, 1H), 1.40 (m, 2H), 0.94 (d, J = 7.5Hz, 3H), 0.93 (d, J = 75 Hz, 3H). MS: (M + H) * = 311 Example 226 Ethyl ester of (+) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3- (c / s-2-chloro-vin-1-yl) -Pyrrolidin -5-carboxylic acid The title compound is prepared according to the method described in Example 222, using trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido) -3-methyl) butyl-3- (c / s-2-chloro-vin-1-yl) -pyrrolidine-5-carboxylic acid instead of the trifluoroacetic acid salt of (±) - (2R, 3S, 5R) , 1'R, 2'S) -2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 28 mg, 46%). 1H NMR (CDCU): d 6.05 (d, J = 7.5Hz, 1H), 5.90 (dd, J1 = 9 Hz, J2 = 6Hz, 1H), 5.31 (d, J = 9Hz, 1H), 4.19 (q, J = 7.5Hz, 2H), 4.06 (m, 1H), 3.82 (t, J = 7.5Hz, 1H), 3.17 (m, 2H) ), 2.45 (m, 1H), 1.98 (s, 3H), 1.67 (m, 1H), 1.60 (m, 1H), 1.37 (m, 2H), 1.27 (t, J = 7.5Hz, 3H), 0.91 (d, J = 7.5Hz, 3H), 0.89 (d, J = 7.5Hz, 3H). MS: (M + H) * = 331 - tS * £ c .-. yes? & Example 227 Intentionally blank.

Example 228 Ethyl ester of (±) - (2R.3S.5R.1'S) -2- (1-Acetamido-3-methyl) butyl-3- (2,2-difluoro-vinyl) -pyrrolidine-5-carboxylic acid The compound of the title is prepared according to the method described in Example 222, using trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl -3- (2,2-difluoro-vinyl) -pyrroline-5-carboxylic acid instead of the trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1 'R, 2'S) -2- (1- acetamide mido-2-hydroxy) buyl-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxylic acid (yield: 28 mg, 57%). 1H NMR (CDCU): d 4.22 (q, J = 7.5 Hz, 2H), 4.14 (m, 1H), 4.03 (m, 1H), 3.29 (br, 1H), 2.85 (m, 1H), 2.52 (m , 1H), 2.01 (s, 3H), 1.77 (m, 2H), 1.64 (m, 2H), 1.49 (m, 1H), 1.38 (m, 1H), 1.29 (t, J = 7.5Hz, 3H) , 0.93 (d, J = 7.5Hz, 3H), 0.90 (d, J = 7.5Hz, 3H). MS: (M + H) * = 333 ^^^ Example 229 Ethyl ester of (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-methyl) butyl-3- (pyrazol-3-yl) -pyrrolidine-5-carboxylic acid The compound of the title is prepared according to the method described in Example 222, using trifluoroacetic acid salt of (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl acid -3- (pyrazol-3-yl) -pyrrolidine-5-carboxylic acid instead of the trifluoroacetic acid salt of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido) 2-hydroxy) butyl-3- (c; 's-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 48 mg, 75.5%). 1H NMR (CDCU): d 7.49 (d, 1H), 7.26 (s, 1H), 6.18 (d, 1H), 4.18 (q, J = 7.5Hz, 2H), 4.12 (m, 1H), 3.91 (t, J = 7.5Hz, 1H), 3.51 (t, J = 7.5Hz, 1H), 3.40 (q, J = 9Hz, 1H), 2.64 (m, 1H), 2.00 (m, 1H), 1.82 (s, 3H), 1. 75 (m, 1H), 1.36 (m, 1H), 1.26 (t, J = 9Hz, 3H), 0.855 (d, 3H), 0.84 (d, 3H). MS: (M + H) * = 337 EXAMPLE 230 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R) -2- (1-Ace tamido-2-ethyl-2-hydroxy) bu til-3- (c / s-propen-1-yl) -pi-1-n-5-carboxylic acid. 230A (t) - (2R.3S.5R, 1'R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-ethyl-2-hydroxy) butyl-3- (c) t-butyl ester / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 41B, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2-t-butyl ester. (1-acetamido-2-oxo) butyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R) t-butyl ester , 1'R) -1-f-butoxycarbonyl 2- (1 -acetamido-1-form i I) methyl-3- (c / 's-propen-1-yl) -pyrrolidine-5-carboxylic acid to give the compound of the title (yield: 0.021 g, 51%). MS: (M + H) * = 469, (M + Na) * = 491, (2M + Na) * = 959, (M-H) - = 467. 230B salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-etl-2-hydroxy) butyl-3- (c / s-propen -1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, 1 ') t-butyl ester. R) -1-f-Butoxycarbonyl-2- (1-acetamido-2-ethyl-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t- butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0039 g, 100%). H NMR (DMSO-de) d7.52 (d, J = 10.3Hz, 1H), 5.45 (m, 1H), 5.28 (m, 1H), 4.32 (m, 2H), 3.68 (t, J = 8.8Hz , 1H), 3.16 (quint., J = 8.5Hz, 1H), 2.41 (dt, J = 13.2.8.3Hz, 1H), 1.81 (s, 3H), 1.59 (m, 1H), 1.53 (dd, J = 6.8.1.5Hz, 3H), 1.52-1.42 (m, 3H), 1.30 (m, 1H), 0.86 (t, J = 7.3Hz, 3H), 0.83 (t, J = 7.3Hz, 3H). MS: (M + H) * = 313, (M + Na) * = 335, (M-H) - = 311, (2M-H) - = 623.

Example 231 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'S) -2- (1- Acetamido-2-hydroxy-2-methyl) pentyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid. 231A t-Butyl ester of (+) - (2R.3S.5R.1'R.2'S) -1-f- B u toxi carbo n il-2- (1 -acetam ido-2-h id roxy- 2-methyl) p-tyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. The title compound was prepared according to the method described in Example 41B, using t-butyl ester of the acid (& ±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl- 2- (1-acetamido-2-oxo) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, t-butyl ester, 3S, 5R, 1'R) -1-f-Butoxycarbonyl 2- (1-acetamido-1-formyl) methyl-3- (c / s-propen-1-yl) -pyridine-5-carboxylic acid and methylmagnesium bromide in place of ethylmagnesium bromide to give the title compound (yield: 0.0285 g, 45%). MS: (M + H) * = 469, (M + Na) * = 491. 231Sulfuric acid acetic acid (±) - (2R, 3S.5R, 1'R, 2'S) -2- (1-Acetate mido-2-h id roxy-2-methyl) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, t-butyl ester, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-2-metii) pentyl-3- (c / s-propen-1-yl) -pyrrolidin-5- carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetam id o-2-hydroxy) butyl ester -3- (c / 's-propen-1-yl) -pi rrol id n-5-carboxylic acid (yield: 0.0040 g, 100%). H NMR (DMSO-de) 69.25 (bs, 1H), 8.75 (bs, 1H), 7.54 (d, J = 10.3Hz, 1H), 5.45 (m, 1H), 5.29 (m, 1H), .37 ( bt, J = 8.3Hz, 1H), 4.22 (t, J = 9.7Hz, 1H), 3.62 (t, J = 8.8Hz, 1H), 3.12 (quint., J = 8.5Hz, 1H), 2.41 (dt) , J = 12.7.7.8Hz, 1H), 1.78 (s, 3H), 1.59 (m, 1H), 1.53 (d, J = 6.8.2.0Hz, 3H), 1.4-1.25 (m, 4H), 1.17 ( s, 3H), 0.81 (t, J = 6.5 Hz, 3H). MS: (M + H) * = 313, (M + Na) * = 335, (M-H) - = 311, (2M-H) - = 623 Example 232 Salt of trifluoroacetic acid of (+) - (2R.3S, 5R.1'R.2'S) -2- (1-Acetamido-2-ethyl-2-hydroxy) pentyl-3- (cis-) acid propen-1-yl) -pyrrole-n-5-carboxylic acid. 232A t-butyl ester of acid (±) - (2R.3S.5R.1'R.2'S) -1-f- Toxic Bu rbonyl-2- (1 -acetam id o-2-ethyl-2-h id roxi) pen ti I-3- (c / s-pro pen-1-yl) -pyrrolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 41B, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-oxo) pentyl-3- (c / 's) t-butyl ester -propen-1-yl) -pyrrolidine-5-carboxylic acid in place of the (±) - (2R, 3S, 5, 1'R) -1-f-butoxycarbonyl 2- (1-acetamido) acid t-butyl ester 1-formyl) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid to give the title compound (yield: 0.0222 g, 33%). MS: (M + H) * = 483, (M + Na) * = 505, (M-H) - = 481. 232B salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1-Acetam ido-2-ethyl-2-h id roxi) pen ti I -3- ( c / s-pro pen-1-yl) -pyrrole-n-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of (±) - ( 2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-ethyl-2-hydroxy) pentyl-3- (c / s-propen-1-yl) - pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl) -butyl ester -3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0035 g, 100%). 1H NMR (DMSO-de) 6 9.1 (bs, 1H), 8.75 (bs, 1H), 7.53 (d, J = 9.8Hz, 1H), 5.44 (m, 1H), 5.28 (m, 1H), 4.35- 4.25 (m, 2H), 3.67 (m, 1H), 3.16 (quint., J = 8.5Hz, 1H), 2.41 (dt, J = 12.8.7.9Hz, 1H), 1.81 (s, 3H), 1.60 ( m, 1H), 1.53 (dd, J = 6.7.1.8Hz, 3H), 1.46 (m, 2H), 1.4-1.20 (, 4H), 0.86 (t, J = 7.3Hz, 3H), 0.82 (t, J = 6.7 Hz, 3H). MS: (M + H) * = 327, (M-H) - = 325, (M + CF3COOH) = 439, (2M-H) "= 651 .3t £ t-z.

Example 233 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R) -2- (1-Acetamido-2-propyl-2-hydroxy) penyl-3- (c / s-propen- 1-yl) -pyrrole din-5-carboxylic acid The title compound was prepared according to the method described in Example 232 but using propyl magnesium bromide instead of ethyl magnesium bromide. 1 H NMR (DMSO-d 6): d 0.81 (t, 3 H), 0.91 (t, 3 H), 1.24-1.49 (m, 8 H), 1. 54 (dd, 3H), 1.60 (m, 1H), 1.81 (s, 3H), 2.41 (m, 1H), 3.15 (m, 1H), 3. 69 (t, 1H), 4.28 (t, 1H), 435 (t, 1H), 5.17 (br s, 1H), 5.28 (td, 1H), 545 (dq, 1H), 7.54 (d, 1H), 8.80 (br s, 1H), 9.12 (br s, 1H). MS: (M + H) * = 341.

EXAMPLE 234 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R) -2- (1-Acetamido-2-ethyl-2-methoxy) butyl-3- (c / s-pro) ? en-1-yl) -pyrrolidine-5-carboxylic acid 234A (±) - (2R.3S.5R, 1'R) -1-t-Butoxycarbonyl-2- (1-Acetam id o-2-ethyl-2- (methylthio) me t-butyl ester useful oxpbu ti l-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester was reacted -1-t-Butoxycarbonyl-2- (1-acetamido-2-ethyl-2-methoxy) butyl-3- (c / s-propen-1-yl) -pyrrplidine-5-carboxylic acid with dimethyl sulfoxide and acetic anhydride in accordance with the method of Marshall, JA in J. Org. Chem. 1979, vol.44, p 2994 to give the title compound. 234A (±) - (2R.3S.5R.1'R.2'S) -1-t-Butoxycarbonyl-2- (1-Acetamido-2-ethyl-2-methoxy) butyl-3 acid t-butyl ester - (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (±) - (2R, 3S, 5R, t-butyl ester, 1 'R, 2'S) - 1 -t- Bu toxic rbon i I-2- (1 -acetamido-2-ethyl-2- (methyl thio) methyloxy) butyl-3- (c / s -propen-1-? l) -pyrrolidine-5-carboxylic acid with Raney nickel according to the procedure of Marshall, JA in J. Org. Chem. 1979, vol. 44, p 2994 to give the title compound Salt of trifluoroacetic acid acid (±) - (2R, 3S.5R, 1'R, 2'S) -2- (1-Acetamido-2-e ti l-2-methoxy) bu til -3 (c / s - propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, t-butyl ester, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-ethyl-2-methoxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in Place of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid.

Example 235 Salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetam id o-2-ethyl-2-methoxy) pentyl-3- (c / s- β-pen-1-yl) -pyrrolidine-5-carboxylic acid The title compound is prepared according to the method described in Example 234 using (±) - (2R, 3S, 5R, 1) t-butyl ester 'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-ethyl-2-hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2- (1-acetamido-2-ethyl-2-hydroxy) butyl-3- (c) acid t-butyl ester / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in 234A.

Example 236 Salt of trifluoroacetic acid of (±) - (2R.3S.5R.1'R.2'S) -2- (1- Acetamido-2-hydroxymethyl-2-hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 236A t-butyl ester of (+) - (2R.3S.5R.1'R.2'S) -1-t-Bu toxic rbonyl-2- (1-Acetic acid-2 - ((1-ethoxy) ethyl) methyl ethyl ester ) -2-hyd roxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (±) - (2 R, 3S, 5 R, t-butyl ester, 1'R, 2 'S) -1-t-Bu-toxicarbonyl-2- (1-acetamido-2-oxo) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid ( 50 mg, 0.11 mmol) with (ethoxyethyloxymethyl) tributylstannane (260 mg, 0.66 mmol) according to the method of Still, WC (J. Am. Chem. Soc, 100, 1481 (1978)) to give the compound of title (yield: 26.8 mg, 43.8%). 1H NMR (CDCU): 5 0.89 (t, 3H), 1.19 (m, 3H), 1.29 (dd, 3H), 1.45 (s, 9H), 1.46 (s, 9H), 1.52-1.73 (m, 8H) , 1.99 (s, 3H), 2.44 (m, 1H), 3.24-3.74 (m, 5H), 3.91-4.22 (m, 3H), 4.49 (m, 1H), 4.62 (m, 1H), 5.37 (m , 1H), 5.64 (m, 1H), 5.97-6.41 (m, 1H). MS: (M + H) + = 557. ^ fa ^ ' 236B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1- Acetate m? Do-2-hidroxy methyl-2-hydroxy) pentyl-3- ( c / s-pro pen- 1 -? l) -pyrrolidine-5-carboxylic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-Butoxycarbonyl t-butyl ester was dissolved i l-2- (1-Acetamido-2- (1-ethoxy-2-ethoxymethyl) -2-h idroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid ( 13.5 mg, 0.024 mmol) in THF (1 mL) was treated with 0.5 N HCl (1 mL) at room temperature for 1 hr. The solvents were removed and the resulting white solid was reacted with trifluoroacetic acid (0.8 mL) in dichloromethane (0.2 mL) at room temperature for 6 hours. The reaction was concentrated in vacuo overnight to give the title compound (yield: 10.7 mg) as an off-white solid 1H NMR (DMSO-de): 5.88 (t, 3H), 1.24-1.38 (m, 4H) , 1.52 (dd, 3H), 1.62 (m, 1H), 1.78 (s, 3H), 2.41 (m, 1H), 3.11 (m, 1H), 3.51 (qAB, 2H), 3.77 (t, 1H), 4.23 (t, 1H), 4.40 (m, 1H), 5.27 (t, 1H), 5.45 (m, 1H), 7.55 (d, 1H), 8.87 (br s, 1H), 9.26 (br s, 1H) . MS: (M + H) * = 329 Example 237 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-allyloxy-2-vinyl) ethyl-3- (c / s-propen-1-yl) -p? rrolidine-5-carboxylic acid 237A t-butyl ester of acid (±) - (2R.3S.5R.1 'R.2'S) -1-t-B or toxic rbon il-2- (1 -acetamido-2-ali lox-2) - vi nyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (2R, 3S, 5R, 1'R, 2'S) -1-t-Butoxycarbonyl-2-reacted (1-acetamido-2-hydroxy-2-vinyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid according to the method described in Example 84A but using allyl iodide in Place of methyl iodide (yield: 28 mg, 80%). MS: (M + H) * = 479, (M-H) - = 477 237B salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'S) -2- (1- Acetate mido-2-allyloxy-2-vinyl) ethyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method which is described in Example 41C, using (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-allyloxy) t-butyl ester 2- vinyl) ethyl-3- (c / s-propen-1-? L) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S, 5R, 1'R, t-butyl ester, 2'S) -1-t-butoxycarbonyl-2- (1- (5-acetamido-2-hydroxy) butyl-3- (c / s-pro pen-1-yl) -pyrrolidin-5-caboxylic acid. (yield: 4 mg, 100%). H NMR (DMSO-d6) 5 7.98 (d, J = 7.8 Hz, 1H), 5.90 (m, 1H), 5.55 (m, 1H), 5.48 (m, 1H), 5.32 (m, 2H), 5.26 (m. m, 2H), 5.16 (m, 1H), 4.28 (m, 2H), 3.96 (m, 1H), 3.79 (m, 1H), 3.73 (m, 1H), 3.66 (m, 1H), 3.26 (m , 10 1H), 2.40 (m, 1H), 1 81 (s, 3H), 1.70 (m, 1H), 1.64 (dd, J = 69, 1 5 Hz, 3H). MS: (M + H) * = 323, (M-H) '= 321.

Example 238 15 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R.1'R.2'S) -2- (1- Acetam-ido- (2,5-dihydrofuran-2-yl)) methyl -3- (cis-propen-1 -i D-pyrrolidine-5-carboxylic acid 238A (±) - (2R, 3S, 5R, VR.S'S ^ -d-Acetamido-l-fS.S-dihydrofuran-S-il-methyl-S-fcis-propen-l-ip t-butyl ester -pyrrolidin-S-carboxylic acid (±) - (2R, 3S, 5R, 1'R, t-butyl ester was reacted, 2'S) -1-f-Butoxycarbonyl-2- (1-acetamido-2-allyloxy-2-vinyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (21 mg, 0.044 mmol) prepared according to the procedure of Example 237A with o / s (tricyclohexylphosphine) benzylidin ruthenium dichloride (IV) [Grubb's catalyst] (7.5 mg, 0.009 mmol) in methylene chloride (5 mL) at 25 ° C. C for 2 hours under a nitrogen atmosphere. The reaction was concentrated in vacuo and the resulting residue was purified by chromatography on silica gel using 75% ethyl acetate / hexanes to give the title compound (yield: 18 mg, 90%). MS: (M + H) * = 451, (M-H) '= 449. 238B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-1- (2,5-dihydrofuran-2-yl)) methyl-3- (c / s-propen-1-yl) -pyrro I idin-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-Butoxycarbonyl-2- (1 -acetamido- 1 - (2, 5-d ih idrofuran-2-yl)) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in place of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxy carbon il t-butyl ester -2- (1-Acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. (yield: 7 mg, 100%). H NMR (DMSO-d6) 6 8.09 (d, J = 8.8 Hz, 1H), 6.10 (m, 1H), 5.87 (m, 1H), 550 (m, 1H), 527 (m, 1H), 468 (m, 2H), 4.58 (m, 1H), 433 (m, 1H), 4.06 (m, 1H), 3.68 (m, 1H) ), 3.18 (m, 1H), 2.40 (m, 1H), 1 85 (s, 3H), 1 68 (m, 1H), 1.60 (dd, J = 68, 1.5 Hz, 3H), MS (M + H) * = 295, (MH) - = 293 Example 239 Salt of trifluoroacetic acid of (±) - (2R, 3S.5R, 1'R, 2'S) -2- (1-Acetamido-2-allyloxy-2-allyl) ethyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid 239A (±) - (2R.3S, 5R, rR.2'S) t-butyl ester -1-t-Butoxycarbonyl-2- (1-acetamido-2-allyloxy-2-allyl) ethyl-3- (c / s-? ropen-1-yl) -pyrrolidine-5-carboxylic acid Reacted (2R, 3S, 5R, 1'R, 2'S) -1-t-Butox? carbonyl-2- (1-acetamido) 2-hydroxy-2-allyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid according to the method described in Example 84A but using allyl iodide instead of methyl iodide (yield: 19 mg, 36%). MS. (M + H) * = 493, (M-H) - = 491. 239B acid trifluoroacetic acid salt (±) - (2R.3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-allyloxy-2-aMI) ethyl-3- (c / s-propen -1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R, 3S, 5R, t-butyl ester, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-Acetamido-2-allyloxy-2-allyl) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid in Place of t-butyl ester of (±) - (2R, 3S, 5R, 1'R, 2'S) -1-t-butoxycarbonyl-2- (1-acetamido-2-hydroxy) buyl-3- ( c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. (yield: 5.7 mg, 100%). 1 H NMR (DMSO-d 6) d 8.06 (dd, J = 8.8 Hz, 1 H), 6.92 (m, 1 H), 6.77 (m, 1 H), 5.50 (m, 1 H), 5.29 (m, 2 H), 5.17 ( m, 1H), 5.05 (m, 2H), 4.27 (m, 2H), 4.10 (dd, J = 12.2, 5.4 Hz, 1H), 3.83 (m, 1H), 3.78 (, 1H), 3.40 (m, 1H), 3.20 (m, 1H), 2.46 (m, 1H), 2.38 (m, 1H), 2.20 (m, 1H), 1.88 (s, 3H), 1.69 (m, 1H), 1.63 (dd, J = 6.8, 1.5 Hz, 3H). MS: (M + H) * = 337, (M + Na) * = 359, (M-H) - = 335.

EXAMPLE 240 Salt of trifluoroacetic acid of (±) - (2R.3S.5R, 1'R, 2'S) -2- (1- Acetamido-1- (3,6-dihydro-2-H-pyran-2- il)) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 240A (±) - (2R.3S.5R.1'R.2'S) t-butyl ester -2- (1-Acetamido-1- (3.6-dihydro-2 - / - / - piran-2-il )) methyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid t-butyl ester (±) - (2R, 3S, 5R, 1 'R, 2'S) -1-f- Bu toxic rbonyl-2- (1-Acetamido-2-allyloxy-2-allyl) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (11.5 mg, 0.023 mmol) prepared in accordance with the procedure of Example 239A was reacted with dichloride of b / s (tricyclohexylphosphine) benzylidin ruthenium (IV) [Grubb's catalyst] (3.8 mg, 0.005 mmol) in methylene chloride (3 mL) at 25 ° C for 3 hours under an atmosphere of nitrogen. The reaction was concentrated in vacuo and the resulting residue was purified by chromatography on silica gel using 75% ethyl acetate / hexanes to give the title compound (yield: 5.7 mg, 53%). MS: (M + H) * = 465, (M + Na) + = 487, (M-H) - = 463 240B salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetate mido- 1 - (3,6-dihydro-2-H-pi ran-2- il)) methyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-1- (3,6-dihydro-2-H-pyran-2) -il)) propyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester (& amp;;) - (2 R, 3S, 5 R, 1'R, 2 'S) -1-f-butocarbon l-2- (1 -acetamido-2-hydroxy) buty I-3- ( c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid. (yield: 5.9 mg, 100%). H NMR (DMSO-d6) 6 8.04 (d, J = 8.8Hz, 1H), 5.77 (m, 2H), 5.50 (m, 1H), 5.25 (m, 1H), 4.21 (m, 2H), 4.14 ( m, 1H), 4.04 (m, 1H), 3.81 (m, 1H), 3.40 (m, 1H), 3.23 (m, 1H), 2.41 (m, 1H), 2.09 (m, 1H), 1.88 (s) , 3H), 1.83 (m, 1H), 1.70 (m, 1H), 1.63 (d, J = 6.8Hz, 3H). MS: (M + H) * = 309, (M + Na) * = 331, (M-H) - = 307 The following compounds were synthesized according to the methods previously described in Examples 1-240 Example 241 Salt of trifluoroacetic acid of (+) - (2R.3S.5R.1'R.2'R) -2- (1-Acetamido-1- (3,6-dihydro-2-H-pyran-2-) il)) propyl-3- (cis-propen-1-yl) -pyrrolidine-5-carboxylic acid 1H NMR (DMSO-d6) d 7.90 (d, 9.1Hz, 1H), 5.79 (m, 2H), 5.48 (m, 1H), 5 23 (m, 1H), 4.43 (m, 1H), 4.24 (m, 2H), 4.17 (m, 2H), 3.73 (m, 1H), 3.64 (m, 1H), 3.19 (m, 1H), 2.42 (m, 1H), 202 (m, 1H), 1.85 (s, 3H), 1.78 (m, 1H), 1.75 (m, 1H), 1.56 (dd, J = 7.5, 1.5 Hz, 3H). MS: (M + H) * = 309, (M + Na) * = 331, (M-H) - = 307.

Example 242 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'S.2'RS) -2- (1-Acetamido-2-hydroxy) pentyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 1H NMR (DMSO) d 7.7 (d, J = 9.8 Hz, 1H), 5.61 (m, 1H), 5.19 (dt, J = 1.8, 11.0 Hz, 1H), 4.33 (dd, J = 6.7, 10.3 Hz, 1H), 3.81 (m, 1H), 3.70 (dd, 1.8, 10.3 Hz, 1H), 3.54 (q, J = 6.1 Hz, 1H), 3.10 (m, 1H), 2.35 (dt) , J = 12.8, 6.8 Hz, 1H), 1.90 (s, 3H), 1.7 (m, 1H), 1.59 (dd, J = 0.7, 73 Hz, 3H), 1 4 (m, 3H), 1 2 (m, 2H), 0.90 (t, J = 6.7 Hz, 3H) MS- (M + H) * = 299 Example 243 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'S, 2'RS) -2-M-Acetamido-2-hydroxy-3-ethoxycarbonyl)? Ropil-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO) 6 7.75 (m, 1H), 560 (m, 1H), 5.29 (m, 1H), 4.55-4.25 (m, 3H), 4.15-4.0 (m, 3H), 3.9-3.6 (m, 3H), 3.15 (m, 1H), 2.45-2.3 (m 2H), 1.9 (s, 3H), 1.8-1.5 (m, 5H), 1.2 (m, 3H). MS: (M + H) * = 343 Example 244 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R.2'S) -2- (1-Acetamido-2-methoxy-2-vinyl) ethyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-de) d 7.91 (d, J = 8.05Hz, 1H), 5.50 (m, 2H), 5.30 (m, ? ß? ^ x.Jt - ?. ~. 3H), 4.27 (m, 1H), 4.23 (m, 1H), 3.75 (m, 1H), 3.48 (m, 1H), 3.23 (m, 1H), 3.15 (s, 3H), 2.40 (m, 1H) ), 1.80 (s, 3H), 1.68 (m, 1H), 1.64 (dd, J = 1.83, 7.32Hz, 3H) MS: (M + H) * = 297, (MH) - = 295 Example 245 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetam-ido-2-ethoxy-2-vinyl) ethyl-3- (c / s-propen -1-yl) -pyrrolidine-5-carboxylic acid 1H NMR (DMS? -dβ) d 7.90 (d, J = 7.85Hz, 1H), 5.57 (m, 2H), 5.48 (m, 3H), 4.27 (m, 1H), 4.22 (m, 1H), 3.77 (m, 1H), 3.60 (m, 1H), 3.46 (m, 1H), 3.23 (m, 2H), 2.39 (m, 1H), 1.80 (s, 3H) ), 1.70 (m, 1H), 1.64 (dd, J = 1.47, 6.73Hz, 3H), 1.12 (t, J = 6.83 Hz, 3H) MS: (M + H) * = 311, (MH) - = 309 Example 246 Salt of trifluoroacetic acid of (±) - (2R.3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-hydroxy-2-fpropeni-2-yl)) ethyl-3- (c) / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-d 6) d 7.69 (d, J = 9.75 Hz, 1 H), 5.47 (m, 1 H), 5.28 (m, 1 H) , 5.03 (m, 1H), 4.86 (m, 1H), 4.40 (m, 1H), 4.30 (m, 1H), 4.18 (m, 1H), 3.97 (m, 1H), 3.68 (m, 1H), 3.21 (m, 1H), 2.43 (m, 1H), 1.82 (m, 1H), 1.73 (s, 3H), 1.64 (s, 3H), 1.59 (m, 3H) MS: (M + H) * = 297, (MH) - = 295 Example 247 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'R) -2- (1- Acetamido-2-hydroxy-2- (propeni-2-yl) ethyl-3- (c / s-propen-1-yl) -pyrrolidin-5-carboxylic acid 1 H NMR (DMSO-de) d 7.65 (d, J = 9.80 HZ, 1H), 5.48 (m, 1H), 5.23 (m, 1H) , 4.99 (s, 1H), 4.88 (s, 1H), 4.46 (m, 1H), .30 (m, 1H), 4.19 (m, 1H), 3. 55 (m, 1H), 3.22 (m, 1H), 2.44 (m, 1H), 1.78 (s, 3H), 1.75 (m, 1H), aaj ...- ..¿.j.f. 1. 65 (s, 3H), 1.58 (dd, J = 1.23, 6.70HZ, 3H) MS: (M + H) * = 297, (M-H) "= 295 Example 248 Salt of trifluoroacetic acid acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2-f1-Acetamido-2-methoxy-2- (propeni-2-yl)) ethyl-3 (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-dβ) 7.77 (d, J = 9.8 Hz, 1H), 5.49 (m, 1H), 5.25 (m, 1H) , 5.07 (m, 1H), 4.94 (m, 1H), 4.32 (m, 1H), 4.25 (m, 1H), 3.75 (m, 1), 3.48 (m, 1H), 3.25 (m, 1H), 3.08 (s, 3H), 2.40 (m, 1H), 1.77 (s, 3H), 1.68 (m, 1H), 1.64 (d, J = 1.22, 6.71Hz, 3H), 1.56 (s, 3H) MS: (M + H) * = 311, (MH) - = 309 Example 249 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R, 1'R) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic H NMR (DMSO-dβ) 5 7.62 (d, J = 9.21Hz, 1H), 5.58 (m, 1H), 5.28 (m, 1H), 4.37 (m, 1H), 3.98 (m, 1H), 3.57 (m, 1H), 310 (m, 1H), 2.45 (m, 1H), 1.92 (s, 3H), 1.76 (m, 1H) ), 1.62 (dd, J = 1.83, 6.72Hz, 3H), 1.24 (m, 5H), 0.84 (t, J = 7.61Hz, 3H), 0.77 (t, J = 7.61Hz, 3H) MS: (M + H) * = 297, (MH) '= 295 Example 250 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetate mido-2-ethyl) bu ti l-3- (c; s-propen-1-yl) - pyrrolidone-5-carboxylic H NMR (DMSO-de) d 7.76 (d, J = 9.2 Hz, 1H), 5.46 (m, 1H), 5.29 (m, 1H), 4.23 (m, 1H), 3.63 (m, 1H), 3.15 (m, 1H), 3.01 (m, 1H), 2.38 (m, 1H), 1.87 (s, 3H), 1.71 (m, 1H), 1.60 (m, 3H), 1.36 ( m, 1H), 1.20 (m, 4H), 0.83 (t, J = 7.3Hz, 6H) MS: (M + H) * = 297, (MH) "= 295 í-Éh- ' Example 251 Ethyl ester of (-) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-? Ropen-1-yl) -pyrrolidin-5- carboxyl v Ethyl ester of (+) - (2S.3S.5S.1'R) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic acid (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-propen-1-yl) ethyl ester was chromatographed -pyrrolidine-5-carboxylic acid (100 mg) in an injection on a chiral HPLC column of dimensions 5 x 30 cm. The column was filled with chiral stationary phase filling Chiralpak AD from Chiral Technologies. The mobile phase consisted of 1: 9 ethanol: hexanes at a flow rate of 117 mL / min.

Two peaks were observed at (24-36) minutes (-) - (2R, 3S, 5R, 1'S) (yield: 45 mg) and at (66-96) min (+) - (2S, 3S, 5S, 1 ' R) (yield: 45 mg). (-) - (2R, 3S, 5R, 1'S) [a] D = -26"(c = 0.78, dichloromethane) Example 252 (-) - (2R, 3S, 5R.1'S) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-propen-1-yl) pyrrolidin-5-carboxylate ammonium Ethyl ester of (-) - (2R, 3S, 5R, 1'S) -2- (1-Acetamido-2-ethyl) butyl-3- (c / s-propen-1-yl) - pyrrolidine-5-carboxylic acid (4.9 mg, 0.0157 mmol) prepared according to the procedure of Example 251 with lithium hydroxide (0.75 mg, 0.0314 mmol) in a mixture of methanol (0.75 mL) and water (0.25 mL) at 0 °. C for 7 hours. Then 0.1 N aqueous hydrochloric acid (1 mL) was added, the reaction was concentrated in vacuo and the resulting residue purified by ion exchange chromatography on a strongly acidic Aldrich Dowex 50WX8-400 resin, the residue was placed on the column and washed with water (5 mL) followed by elution using 0.5N aqueous ammonium hydroxide to give the title compound as a colorless solid (yield: 3.9 mg, 83%). [a] D = -40 °, c = 0.08 ( water) .1H NMR (DMSO-d6) 57.71 (d, J = 9.2 Hz, 1H), 5.38 (m, 1H), 5.29 (m, 1H), 3.92 (m, 1H), 3.65 (t, J = 8.5 Hz, 1H), 3.43 (m, 1H), 3.33 (m, 1H), 2.98 (m, 1H), 2.23 (m, 1H), 1.76 (s, 3H), 1.54 (dd, J = 6.7, 1.8 Hz , 3H), 1.46 (m, 2H), 1.23 (m, 1H), 0.84 (t, J = 7.3 Hz, 3H) MS: (M + H) = 285, (M + Na) + = 307, ( MH) - = 283. [a] or 40 °, (c = 0.08, water).

Example 253 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1- Ace-tamido-2, 3-d imethoxy) propi l-3- (c / s- propen-1-yl) -pyridine n-5-carboxylic acid H NMR (MeOD-d3) d.7.8 (d, J = 9.3Hz, 1H), 5.49-5.43 (m, 1H), 5.25 (dd, J = 1.95, 9.3Hz, 1H), 4.38-4.31 (m, 2H), 3.57-3.50 (m, 1H), 3.46 (dd, J = 4.9, 10.3Hz, 1H), 3.42 (s, 3H), 3.35-3.32 (m, 2H), 3.27 (s, 3H), 3.16- 3.09 (m, 1H), 2.46-2.40 (m, 1H) , 1.80 (s, 3H), 1.72-1.65 (m, 1H), 1. 55 (d, J = 6.8Hz, 3H). MS: (M + H) * = 315, (M + Na) * = 337, (M-H) - = 313, (M + CI) = 349, (2M-H) - = 627.

Example 254 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R, 2'R) -2-M-Ace tamido-2,3-di methoxy) propyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid H NMR (MeOD-dj) d 804 (d, J = 85Hz, 1H), 5.52-548 (m, 1H), 5.27-5.22 (m, 1H), 4.32 -4.25 (m, 2H), 3.74-3.71 (m, 1H), 3.53 (dd, J = 24, 10.1Hz, 1H), 3.33-3.25 (m, 2H), 331 (s, 3H), 3.25 (s) , 3H), 3.21-3.17 (m, 1H), 2.42-2.36 (m, 1H), 1.86 (s, 3H), 1.71-1.63 (m, 1H), 1.62 (d, J = 7.3Hz, 3H). MS: (M + H) * = 315, (M + Na) * = 337, (M-H) - = 313, (M + CI) - = 349, (2M-H) - = 627 Example 255 Salt of the acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-Acetamido-2-hydroxyethyl-2-hydroxy) pentyl-3- ( c; s-propen-1-yl) -pyrrolidin-5-carboxylic acid 1 H NMR (DMSO-d 6): 57.60 (m, 1 H), 5.46 (m, 1 H), 5.30 (m, 1 H), 4.54 (m, 1H), 4.35 (m, 1H), 403 (m, 1H), 3.96 (m, 1H), 3.69 (m, 1H), 3.15 (m, 1H), 2.40 (m, 1H), 1.98 ( m, 2H), 1.80 (s, 3H), 1.70-1.50 (m, 5H), 1.38 (m, 3H), 083 (m, 3H). MS. (M + H) + = 343, (M-H) - = 341 Example 256 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R.1'R) -2- (1-Acetam-ido-2- (3-pentyloxy)) ethyl-3- (c / s-propen-1) -yl) -pyrrolidine-5-carboxylic acid 1H NMR (MeOD-d3) d 5.69-5.59 (m, 1H), 5.33-5.25 (m, 1H), 4.39 (m, 1H), 4.34 (dd, J = 7.8, 10.2Hz, 1H), 3.73 (dd, J = 4.8, 10.2Hz, 1H), 3. 58-3.47 (m, 2H), 3.38-3.24 (m, 1H), 3.27-3.20 (m, 1H), 2.61-2.52 (m, 1H), 2.02 (s, 3H), 1.90-1.78 (m, 1H) ), 1.70 (dd, J = 1.7, 6.8Hz, 3H), 1. 60-1.50 (m, 4H), 0.92 (t, J = 7.5Hz, 6H) (M + H) * = 327, (M + Na) * = 349 Example 257 Salt of acid trifluoroacetic acid (±) - (2R.3S, 5R, 1'S) -2- (1-Acetamido-2- (3-pentyloxy)) ethyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid H NMR (MeOD-d3) d 573-566 (m, 1H), 532-5.25 (m, 1H), 4.36 (dd, J = 7.8, 10.2Hz, 1H), 4.09 (m, 1H), 3.68 (dd, J = 6.1, 10.2Hz, 1H), 3.61 (d, J = 4.4Hz, 2H), 3.35-323 (m, 1H), 3.24-3.16 (, 1H), 2.65-2.55 ( m, 1H), 2.03 (s, 3H), 1.92-1.80 (m, 1H), 1.70 (dd, J = 2.0, 7.1Hz, 3H), 1.59-1.47 (m, 4H), 094-0.88 (m, 6H) (M + H) * = 327, (M + Na) * = 349 Example 258 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2-ethoxy-3-v? Nyl) propyl-3- (c / s- propen-1-yl) -pyrrolidine-5-carboxylic acid H NMR (DMSO-de) d 8.01 (d, J = 8.6Hz, 1H), 5.76 (m, 1H), 5.49 (m, 1H), 525 (m, 1H), 5.05 (m, 2H), 428 (m, 1H), 4.02 (, 1H), 3.77 (m, 1H), 362 (m, 1H), 3.36 (m, 1H) , 3.29 (m, 1H), 3 18 (m, 1H), 2.43 (m, 1H), 2.38 (m, 1H), 2.16 (m, 1H), 1.87 (s, 3H), 1.69 (m, 1H) , 1 63 (dd, J = 6.7, 1.2 Hz, 3H), 1.12 (t, J = 6.7 Hz, 3H) MS: (M + H) = 325, (MH) - = 323 Example 259 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-allyloxy) ethyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic acid 1H NMR (DMSO-de) d 9.16 (m, 2H), 8.13 (d, J = 7.5Hz, 1 H), 5.88 (m, 1H), 5.50 (m, 1H), 5.15-5.32 ( m, 3H), 4.35 (m, 2H), 3.95 (m, 2H), 3.61 (m, 1H), 3.40 (m, 2H), 3.20 (m, 1H), 2.40 (m, 1H), 1.87 (s) , 3H), 1.72 (m, 1H), 1.62 (d, J = 6.2.3H) MS: (M + 1) = 297, (M + 23) = 319, (2M + 23) = 615 Example 260 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R.2'RS) -2- (1-Acetamido-2-hydroxy-2- (2-ethoxycarbonyl)) pentyl-3 - (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid 1 H NMR (DMSO-de): d 7.57 (d, J = 10 Hz, 1 H), 5.45 (m, 1 H), 5.29 (m, 1 H) ), 4.35 (m, 1H), 4.09 (m, 1H), 3.68 (, 1H), 3.44 (m, 1H), 3.17 (m, 1H), 2.87 (m, 1H), 2.64 (m, 1H), 2.39 (m, 1H), 1.80 (s, 3H), 1.65-1.56 (m, 2H), 1.53 (m, 3H), 1.50-1.30 (m, 3H), 1.21 (t, J = 7.5Hz, 3H) , 0.80 (t, J = 7.5Hz, 3H). MS: (M + H) * = 385, (M-H) = 383 Example 261 Salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'S.3'R) -2- (1- Acetamido-3,4-dih id roxi) buti l-3- (c / s-propen -1-i0-? -rolidin-5-carboxylic acid 1H NMR (CD3OD) 6 5.58-5.70 (m, 1H), 5.24-5.38 (m, 1H), 4.34-4.50 (m, 2H), 3.58-3.72 (m, 2H), 3.42-3.48 (d, 2H), 2.50-2.63 (m, 1H), 2.04 (s, 3H), 1.77-1.95 (m, 1H), 1.65 -1.76 (m, 4H), 1.50-1.63 (ni, 1H). MS: (M + H) * = 301 Example 262 Salt of acid trifluoroacetic acid (±) - (2R, 3S, 5R, 1'S.3'S) -2- (1-Acetamido-3,4-dihydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine -5-carboxylic acid 1H NMR (CD3OD) 6 5.58-5.72 (m, 1H), 5.25-5.37 (m, 1H), 4.30-4.45 (m, 2H), 3.63-3.77 (m, 2H), 3.44-3.49 (d, 2H), 2.50-2.63 (m, 1H), 2. 03 (s, 3H), 1.76-1.95 (m, 2H), 1.65-1.75 (m, 4H). MS: (M + H) * = 301 at EXAMPLE 263 Exit of trifluoroacetic acid from (±) - (2R.3S.5R.1'R) -2- (1-Acetamido-2-methoxy) etl-3- (c / s-pro? In) 1-l) -pyrrolidine-5-carboxylic acid 263A (±) - (2R, 3S.5R.1'R) -1-f-Butoxycarbonyl-2- (1-Acetam-ido-2-methoxy) eti l-3- (c / s) acid t-butyl ester -propen-1 -i P-pirro lid i n-5-ca rboxi Meo.

The title compound was prepared according to the method described in Example 84A, using (±) - (2R, 3S, 5R, 1'R) -1-f-butoxycarbonyl-2-t-butyl ester. (1-acetamido-2-hydrox?) Et? L-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid instead of (±) - (2R, 3S) t-butyl ester , 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy) butyl-3- (c / s-propen-1-yl) - pyrrolidium-5-carboxylic acid (yield: 4.2 mg, 20%). MS: (M + H) * = 427, (M + Na) * = 449, (M-H) = 425. 263B salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R) -2- (1-Acetamido-2-methoxy) ethyl-3- (c; s-propen-1-yl) - pyrrolidin-5-carboxylic acid. The title compound was prepared according to the method described in Example 41C, using acid t-butyl ester (±) - (2 R, 3S, 5 R, 1'R) -1 -fb or toxicarbon il-2- (1 -acetam ido-2-methoxy) eti I-3- (c / s-propen-1) -yl) -pyrrolidine-5-carboxylic acid instead of t-butyl ester of (±) - (2 R, 3S, 5 R, 1'R, 2'S) - 1-f-bu toxic rbon il-2- ( 1 -acetam id or-2-hydroxy) butyl-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 0.0031 g, 100%). 1H NMR (DMSO-dβ) d 8.12 (d, J = 7.9Hz, 1H), 5.50 (m, 1H), 5.23 (m, 1H), 4.33 (m 1H), 3.56 (dd, J = 9.7.8.0Hz) , 1H), 3.4-3.3 (m, 2H), 326 (s, 3H), 3.19 (, 1H), 2.39 (dt, J = 12.8.7.3Hz, 1H), 1.86 (s, 3H), 1.71 (m , 1H), 1.61 (dd, J = 6.7.1.8Hz, 3H). MS: (M + H) * = 271, (M + Na) * = 293.

Example 264 Salt of trifluoroacetic acid of (±) - (2R, 3S, 5R, 1'R.2'S) -2- (1-Acetamido-2-hydroxy-3-dimethyl) butyl-3- (c / s) -propen-1-yl) -pyrrolidin-5-carboxylic acid. 264A (+) - (2R.3S.5R.1'R.2'S) t-butyl ester -1-f- Butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-dimethyl) butyl-3- (c / s-? ropen-1-yl) -pyrrolidine-5-carboxylic acid. The title compounds were prepared according to the method described in Example 41B, using t-butyl lithium instead of ethyl magnesium bromide to give t-butyl ester of the acid (±) - (2R, 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1-acetamido-2-hydroxy-3-dimethyl) butyl-3- (c / s-propen- 1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.5 mg, 11%) (±) - (2R, 3S, 5R, 1'R, 2'S) MS: (M + H) * = 469; (M-H) '= 467. 264B salt of acid trifluoroacetic acid (±) - (2R.3S.5R.1'R.2'S) -2- (1 -Acetam id o-2-h id roxi-4-vinyl) bu til-3- ( c / s-propen-1 -i D-pyrrole-n-5-carboxylic acid The title compound was prepared according to the method described in Example 41C, using (±) - (2R) t-butyl ester , 3S, 5R, 1'R, 2'S) -1-f-butoxycarbonyl-2- (1 -acetamido-2-hydroxy-3-dimethyl) butyl-3- (c / s-propen-1-yl) ) -pyrrolidine-5-carboxylic acid instead of (+) - (2R, 3S, 5R, 1'R, 2'S) t-butyl ester) -1-f-butoxycarbonyl-2- (1-acetamido-2-h) Droxi) buti l-3- (c / s-propen-1-yl) -pyrrolidine-5-carboxylic acid (yield: 2.3 mg, 100%). 1 H NMR (D20) d 5.40 (m, 1H), 5.10 (t, J = 5.5Hz, 1H), 4.13 (t, J = 9.2Hz, 1H), 3.46 (m, 1H), 3.22 (d, J = 7.3Hz, 1H), 3.00 (m, 1H), 2.41 (m, 1H), 1.70 (s, 3H), 1.45 (m, 1H), 1.39 (d, J = 4.9Hz, 3H), 1.07 (t, J = 5.5Hz, 1H), 0.70 (s, 9H) MS: (M + H) * = 313. Using the described methods and the general knowledge of specialists in the field, it is possible to prepare The compounds of the invention which are represented by taking a core from Table 1 (where Ac is acetyl), a Y substituent of Table 2, a substituent R of Table 3 and a substituent R3 of Tables 4a, 4b, 4c, 4d, 4e, 4f or 4g ^ & s ^^^ g ^^ Table 1 Table 2 F3C F HN ^ N HN- «. Cl 13 16 H_Q H3q F3Q Cl F3C 18 20 H3C F HN J =. { H3C K ™ 21 22 23 F3C F-.C ^ S * N = < F F3C Cl 26 27 , c? ? Et. ZX - F3C H .c. H3C H3C, 53 .N. , N. 1fQ N * > ? N-N 45 46 47 48 53 54 55 H3C CH Cl C, = ya c? c? H3C. 74 75 .CF? 3 Cl Cl CH, F, C F3C 'H ^ - C'l ^ T-Cl, CH3 H3Q Cl H3C cr F3C. 'H, C 85 86 87 88 Cl., CH3 H3Q. Cl H3C CH3 Cl CH3 H, C 90 91 H3C F3Q H, C, CF3 H3C CB F3C H3C ^ ~ H3C ^ ~ F3C 105 106 107 108 H3Q CF, F3C .CH: F3 F3C CH3 H3C 3 109 110 111 112 F3C Cl F3C Cl F3C _ / CI F3C \ _ C 3 F3C > = cl > =. ß > -L 129 130 131 132 F3C CH3 clwCH3 HjCw qF3 H3C F F t-3 ¿t, ~ y ~~ Z p X ~ P F3C ~ 157 158 159 160 170 171 172 H2N. NH _ ~ H2N-V, NH Table 3 -H 1 ~ CH 3 -CH 3 3 CH3 CH3 CH3 CH3? K CH3 rj Table 4a H, C OH OH CH, x H.C ^^^ QH OH 3 OCH3 H3C OCHa 3 H3C X OCH3 CH3 to OCH 17 18 19 20 49 50 51 Table 4b 32 ? 3 ^ OH H ^ 3 OH HH? OH ~ CHJ ^ OH CHj 37 38 39 40 63 64 I 2 3 1 4 54 OH OH OH 3 Jf ~ CH3 CH3 CH3"CH H3C CH3 OH OH 34 35 I 36 H3C H3C .H3C- ^ CH3 x CH3 ti CH3 CH3 37 38 39 40 «J • CH, \ '-? S" », and -cCH, T ™, 42 43 44 ^ g | g ^ CH3 H3C H3C 'CH3 CH3 CH3 CH3 OH OH OH OH 62 63 64 and--, ~~ OH T OOHH T ~ OH OH OA, ^ 3 H ¿CH 3C CH3 69 72 "Ana" . - -. 145 146 147 148 CH3 and H, C CH3 - CH3"C" H3 -UT C "? H3J" fU ~ CH3 '^ i.

H3C CH3 CH3 CH3 H3C CH3 163 164 165 166 H: CH3 and CH3 CH3 and CH3 H3C ™ cHa ^ | and CH t ^ U U r L l OH OH OH OH 171 172 173 174 ? 73 CH3 ü s CH3 ^ "3 183 184 185 186 195 196 197 198 CH3 CH3 CH3 CH3 CH3 CH3 CH3 H3C CH3 CH3 CH3 H3C CH3 199 200 201 202 227 228 229 230 CH; cuu H3C H3C CH3 CH3 259 260 261 262 283 284 285 H i C i H3 J ¡H3C. 287 288 289 290 Table 4d ¿¿¿¿Y ** - ¿p H * c-¿y 12 ! &Ó & ó ® & amp; Table 4e CCHH33 H3C. OH H3C ^ .. .OH. OH OH OH OH OH OH 25 26 27 28 54 55 Table 4f ZX- CH3 -CH3 -CCHH, 3 - CH3 CH3 H3C CH3 .z CH3 CH3 C CHH33 and C and Hn33 and | C? Hp33 | || kX? "CH3 k ~? -CH3 kA-CHj k / k H3 J CH3 CH3 CH3? CH3 H3C CH3 CH3 CH3 H3C CH3 21 22 23 24 52 77 78 79 -j ", tj rz" rz 81 82 83 84 109 110 112 Table 4g -and- CH 3 -and H3C ?; CH3 HsC ^^ - CH, k¿, -CH3"CH3 OH or OHH OH OOH 2 H -rCH3 Hjc f / -CH > ? trc »> U [-CH, "3 ° OH OR OHH ^ OH, OH 10 45 46 OCH3 HaC H3C? C:. -OCHa k "0 OCCHH33 - -OCH3 H3 CH3 CH3 49 52 CH, CH3 - ^., / H3 OH O CHa, C / \ O O; HH 71 CH 3 OH -OH OH -OH CH 3 CH, CH 3 CH, 102 103 104 H 130 131 H3C_J-0CH3 kli-OCH3 d- -OOCCHH3 \ I OCH3 ^ CH3-OCH * -OCH3-OCH3 185 186 187 188 H 190 191 192 0H 205 &"206 o00" '207 0CH "208 12 -CH3 -CHH33 O;. C CH3 (b O cCH3 218 219 220 ... and & - - x The ability of the compounds of the invention to inhibit neuraminidases in vitro can be determined according to the method described below.

Neuraminidase Inhibition Assay: Influenza A / N 1 / PR / 8/34 virus was cultured in the allantoic cavity of fertilized eggs and purified by sucrose density gradient centrifugation (Laver, WG (1969) in "Fundamental Techniques in Virology "(K Habel and N. P. Salzman, eds) pp. 92-86, Academic Press, New York) The influenza virus A / N2 / Tokyo / 3/67 was obtained from tissue culture supernatants of cultured virus with MDCK cells. B / Memphis / 3/89 virus neuraminidases were prepared by virus digestion with TPCK-trypsin followed by centrifugation and subsequent purification of the neuraminidase catalytic fragment using sucrose density gradient centrifugation and dialysis as described above (Air, GM, Laver, WG, Luo, M., Stray, S.J., Legrone, G., and Webster, RG (1990) Virology 177, 578-587). In the neuraminidase inhibition assays, the enzyme activity neuraminidase associated with the complete virus A / N 1 / PR / 8/34 or A / N2 / Tokyo / 3/67 or the main catalytic fragment of B / Memphis / 3 / was used. 89 The whole virus or the catalytic fragment was appropriately diluted with pH buffer containing 20 mM N-ethylmorpholine, 10 mM calcium chloride, pH 7.5 on the day of the experiment. Neuraminidase inhibition assays are carried out in pH buffer of 20 M N-ethylmorpholine, 10 mM calcium chloride, pH 7.5 with 5% DMSO. The reaction mixtures included neuraminidases, inhibitor (test compound) and substrate of 4-methylumbelliferilsialic acid 20-30 μM in a total volume of 200 μl and were placed in 96-well U-shaped white plates. Typically, five to eight concentrations of inhibitor were used for each measurement of Ki values. The reactions were started with the addition of enzyme and allowed to advance for 30-60 minutes at room temperature. The fluorescence of each plate cavity was measured once per minute during the reaction period with a Fluoroskan II plate reader (ICN Biomedical) equipped with excitation and emission filters of 355 +/- 35 nm and 460 +/- 25 nm, respectively. The plate reader was controlled with the DeltaSoft I I software (Biometallics) and a Macintosh computer. If the compound exhibited linear reaction rates during the reaction period, then reaction rates for the dose-response study were fitted to equation 1 using a non-linear regression program (Kaleidagraph) in order to determine the Ki value global (Segel, I. H. (1975) in Enzyme Kinetics, pp. 105-106, Wiley-lnterscience, New York). (1 - V¡ / V ") = [1] /. { [I] + Ki (1 + [S] / Km)} Equation 1 In equation 1, V, and V "represent the inhibited and uninhibited reaction rates, respectively, and Km = 16 - 40 μM according to the neuraminidase strain evaluated For those compounds that showed a slow binding inhibition (Morrison, JF (1982) Trends Biochem, Sci.7, 102-105), a second experiment was carried out in an identical way to the first, except that the neuraminidase and the inhibitor were preincubated in the absence of substrate for 2 hours at room temperature before initiating the reactions with the substrate. The analysis of the data for the resulting linear velocities was carried out as described above. Equation 2 was used to measure Ki values in the sub-nanomolar range (Morrison, JF and Stone, S. R. (1985) Comments Mol.Cell Biophvs.2, 347-368).

V = A { square root. { (Ki '+ lt-Et)? 2 + 4Ki? T} - (Ki '+ lt- Et)] Equation. 2 In Equation 2, V = velocity; A = akca, [S] / 2 (Km + [S]); a is a factor for converting the fluorescence units to molar concentrations; Ki '= Ki (1 + [S] / Km); It = total concentration of inhibitor and Et = total active concentration of neuraminidase. The compounds of the invention 'inhibit influenza A neuraminidase and influenza B neuraminidase with Ki values between 0.1 nanomolar and 500 micromolar approximately. Preferred compounds of the invention inhibit influenza A neuraminidase and influenza B neuraminidase with Ki values between 0.1 nanomolar and 3.5 micromolar approximately. The ability of the compounds of the invention to inhibit plaque formation in cell culture can be determined by the method described below.

Inhibition assay of plaque formation in cell culture Cell cultures: MDCK cells obtained from American Type Culture Collection in the Dulbecco Modified Eagle Medium (DM EM) with high g-lucy content (GibcoBR L) supplemented with 10% fetal bovine serum (J RH Biosciences), HEPES 40 M pH regulator (GibcoBRL) and antibiotics (GibcoBRL). A routine culture of the cells was carried out in flasks or rotary bottles at 37 ° C and C? 2 5%. At the confluence point the cells were reduced to a density of 500,000 cells in one ml using a trypsin / EDTA (GibcoBRL) treatment of the monolayer followed by centrifugation, resuspension and dilution of the cells in the culture medium. The cells were plated with a volume to surface area ratio of 1 ml per 1 cm 2 of growth surface.

Plaque assay protocol: At the point of confluence of MDCK cells the culture medium was removed from 6-well plates and the cells were coated with 1.5 ml of assay medium (DMEM with 1% fetal bovine serum, pH regulator 40 mM HEPES and antibiotics) containing a virus premix (influenza A / Tokyo / 3/67 [H2N2]) (40-100 plaque forming units) and the test compound at a 2x concentration. Plates were placed on a vibrating plate and incubated for 2 hours at room temperature. During the period of adsorption of the virus, the agar coating medium was prepared. In a microwave oven, 2X agarose (final concentration of 0.6% agarose) was dissolved in coating medium (DMEM with 40 mM H EPES pH regulator) and then placed in a 48 ° C water bath to balance the temperature. Once the virus adsorption period was complete, 1 -5 ml of agar was added to the medium and mixed with the medium containing 1.5 ml of virus and test compound per cavity. The cultures were incubated at 35 ° C for the period necessary for the development of plaques, usually several days. The plates were fixed with 3.7% formalin in PBS for 20 minutes followed by removal of the agar coating and staining with 0.1% crystal violet in distilled water for 15 minutes. The plates were then counted and the ECS0 concentration was determined from multiple concentrations of the test compound using regression analysis.

Virus stock solutions: Stock solutions were prepared in rotating bottles with confluent MDCK incubated at 37 ° C in DMEM supplemented with FCS 1%, pH regulator HEPES 40 mM and antibiotics. The bottles were inoculated with a multiplicity of infection of approximately 0.1 plaque-forming units for each cell. The rotary bottles were harvested after the end of the cytopathic effect of the virus was observed. Stock solutions were prepared from the supernatant resulting from a low speed centrifugation of the medium and cell lysate. The stock solutions were titrated and then stored at -80 ° C.

The compounds of the invention provided inhibition of plaque formation for influenza A / N2 / Tokyo virus in M cells DCK with EC50 values between 100 micromolar and 1 nanomolar approximately. Preferred compounds of the invention provided inhibition of plaque formation for influenza A / N2 / Tokyo virus in MDCK cells with EC50 values between about 1 micromolar and about 1 nanomolar. The compounds of the invention can be evaluated for their antiviral activity in vivo using the method described below.

In Vivo antiviral efficacy method Female BALB / c mice (sevoflurane) were anaesthetized and then inoculated intranasally (IN) with 0.1 ml of influenza A VR-95 (Puerto Rico PR8-34) at 10-2 (diluted from of the frozen stock solution). This viral concentration produced the disease consistently in the mice within 5 days after inoculation. The animals were treated 4 hours before infection and 4 hours after infection, and periodically after, with one of the following therapies: no treatment; test compound (100; 25; 6.25; 1.39 mg / kg / day BI D, PO); or with vehicle (sterile water BID, PO). A group of ten animals (called control) was inoculated with 0.9% saline. The survival percentage was determined. On day five the lungs were harvested, weighed and assigned grades of 0, 1, 2, 3 or 4 on the basis of percent consolidation (0; 10-20; 25-50; 50-75; 75-100 %, respectively). In addition, each pair of lungs was subjected to image analysis in order to determine the objective percentages of lung consolidation. The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include, but are not limited to, the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphor sulfonate, digluconate, cyclopentanpropionate, dodecyl sulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate , fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate (isethionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesulfonate and undecanoate. In addition, basic groups containing nitrogen can be quaternized with agents such as lower alkyl halides, such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkylsulfates as dimethyl, diethyl, dibutyl and diamyl sulfates, long chain halides, such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides such as benzyl and phenethyl bromides, and others. In this way, soluble or dispersible products are obtained in water or oil. Examples of acids that can be used to form acid addition salts acceptable for pharmaceutical use include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, and organic acids such as oxalic acid, maleic acid, succinic acid and acid. citric. Other salts include salts with alkali metals or alkaline earth metals, such as salts with sodium, potassium, lithium, calcium or magnesium or with ammonium or N (R **) 4+ (where R ** is lower alkyl). In addition, salts of the compounds of this invention with one of the natural amino acids are also contemplated. Preferred salts of the compounds of the invention include hydrochloride, methanesulfonate, sulfonate, phosphonate and isethionate. The compounds of formula I, II and III of this invention may contain a substituent which is an acidic group (for example, -C -C ?H, -S? ?H, -S02H, -P03H2, -P02H). The compounds of formula I, II and III of this invention that contain a substituent that is an ester of said acid group are also included in this invention. These esters can serve as prodrugs. The prodrugs of this invention are metabolized in vivo to provide the The aforementioned acidic substituent of the related compound of Formula I, II and III Prodrugs can also serve to increase the solubility of these substances and / or absorption from the gastrointestinal tract. These prodrugs may also serve to increase the solubility for intravenous administration of the compounds. The prodrugs can also serve to increase the hydrophobicity of the compounds. Prodrugs may also serve to increase the oral bioavailability of the compounds by increasing absorption and / or decreasing the first step of metabolism. The prodrugs can also serve to increase the tissue penetration of the compounds, which leads to an increase in the activity in the infected tissues and / or a reduction in the clearance rate. Such esters which are contemplated by this invention include: alkyl esters, especially lower alkyl esters, including, but not limited to, esters of ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n -pentyl and similar; alkoxyalkyl esters, especially lower alkoxy lower alkyl esters, including, but not limited to, esters of methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, isopropoxymethyl, t-butoxymethyl and the like; alkoxyalkoxyalkyl esters, in particular, lower alkyl esters substituted with alkoxyalkoxy, including, but not limitations, esters of 2-methoxyethoxymethyl and the like; aryloxyalkyl esters, especially lower alkyl esters substituted with aryloxy, including, but not limited to, phenoxymethyl esters and the like, wherein the aryl group may be substituted or unsubstituted, as defined hereinbefore; haloalkoxyalkyl esters, in particular, lower alkyl esters substituted with haloalkoxy, including, but not limited to, 2,2,2-trichloroethoxymethyl esters and the like; alkoxycarbonylalkyl esters, especially lower alkyl esters substituted with lower alkoxycarbonyl, including, but not limited to, esters of methoxycarbonylmethyl and the like; cyanoalkyl esters, in particular, lower alkyl esters substituted with cyano, including, but not limited to, esters of cyanomethyl, 2-cyanoethyl and the like; thioalkoxymethyl esters, in particular methyl esters substituted with lower thioalkoxy, including, but not limited to, methylthiomethyl, ethylthiomethyl esters and the like; alkylsulfonylalkyl esters, especially lower alkyl esters substituted with lower alkylsulfonyl, including, but not limited to, 2-methanesulfonylethyl esters and the like; arylsulfonylalkyl esters, in particular, lower alkyl esters substituted with arylsulfonyl, including, but not limited to, esters of 2-benzenesulfonylethyl and 2-toluenesulfonylethyl and the like; aciloxialquilesteres especially esters substituted with lower alkylacyloxy lower alkyl, including but not limited to, esters formyloxymethyl, acetoxymethyl pivaloyloxymethyl, acetoxyethyl, pivaloyloxyethyl and the like cicloalquilcarboniloxialquilesteres including, but not limited to, esters ciclopentancarboniloximetilo nca cyclohexa rbon yloxy methyl ciclopen tanca iloxietilo rbon , cyclohexanecarbonyloxyethyl and the like, aplcarbonyloxyalkyl esters including, but not limited to, benzoyloxymethyl esters and the like, (alkoxycarbonyl) alkylesters, especially lower alkyl esters substituted with (lower alkoxycarbonyloxy) including, but not limited to, esters of methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, 1- (methox? carbon? lox?) et? lo, 2- (ethoxy? carbon? lox?) et? lo and the like, (c? cloalk? lox? carbon? lox?) alk? esters, in particular, lower alkyl esters substituted with (cycloalkyloxycarbonyloxy), including but not limitations, esters of cyclohexyloxycarbonyloxymethyl, cyclopentyloxycarbonyloxyethyl, cyclohexyloxycarbomloxypropyl and the like, oxydioxolemylmethols including, but not limited to, esters of (5-phenol-2-oxo-1,3-d-oxolen-4-? l) meth, [ 5- (4-met? Lfen? L) -2-oxo-1, 3-d? Oxolen-4-? L] met? Lo, [5- (4-methox? Phen? L) -2-oxo- 1,3-d? Oxolen-4-ylmethyl, [5- (4-fluorophen? L) -2-oxo-1,3-d? Oxolen-4-? L] met? Lo, [5- (4- chlorof in? l) -2-oxo- 1, 3-d? oxolen-4-? l] met? lo, (2-oxo- 1, 3-d? oxolen-4-) il) methyl, (5-methyl-2-oxo-1, 3-dioxolen-4-yl) methyl, (5-ethyl-2-oxo-1,3-dioxolen-4-yl) methyl, (5-propyl) -2-oxo- 1, 3-dioxolen-4-yl) methyl, (5-i sop rop i 1-2-0X0- 1, 3-dioxolen-4-yl) methyl, (5-butyl-2-oxo -1,3-dioxolen-4-yl) methyl and the like; phthalidyl esters, wherein the phenyl ring of the phthalidyl group is or is not substituted as defined hereinabove, including, but not limited to, phthalidyl, d-methyl, talidyl, dimethoxyphalidyl esters and the like; arylesters, including, but not limited to, esters of phenyl, naphthyl, indanyl and the like, arylalkyl esters, especially, lower alkyl esters substituted with aryl, including, but not limited to, esters of benzyl, phenethyl, 3-phenylpropyl, naphthylmethyl and the like , wherein the aryl part of the arylalkyl group is substituted or unsubstituted as defined hereinbefore; dialkylaminoalkyl esters, especially dialkylamino-substituted lower alkyl esters, including, but not limited to, esters of 2- (N, N-dimethylamino) ethyl, 2- (N, N-diethylamino) ethyl and the like; alkyl (heterocyclic) esters, especially lower alkyl esters substituted with heterocycles, wherein the heterocycle is a nitrogen-containing heterocycle, including, but not limited to, methyl esters (heterocyclic) and the like, wherein the heterocyclic part of the alkyl group (heterocyclic) is substituted or not as defined above in this document; Y carboxyalkyl esters, especially lower alkyl esters substituted with carboxy, including, but not limited to, carboxymethyl esters and the like; and similar. Esters as preferred prodrugs of the compounds of Formula I, II and III which contain acid are lower alkyl esters, including, but not limited to, esters of ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl and benzyl esters , wherein the phenyl ring is substituted or not as defined hereinabove. The methods for the preparation of prodrug esters of the compounds of. Formula I, II and III are well known in the art and include: reacting the acid with the corresponding halide (eg, chloride or acyl chloride) and a base (eg, triethylamine, DBU, N, N-dimethylaminopyridine) and the like) in an inert solvent (e.g., DMF, acetonitrile, N-methylpyrrolidone and the like); reacting an activated derivative of the acid (eg, acid chloride, sulfonyl chloride, monochlorophosphonate and the like) with the corresponding alcohol or alkoxide salt; and similar.

Other examples of prodrugs of the present invention include esters of hydroxyl-substituted Formula I, II and III compounds that have been acylated with a blocked or unblocked amino acid residue, a phosphate function, a residue hemisuccinate, an acyl residue of formula R100C (O) - or R 00C (S) -, where R 0 ° is hydrogen, lower alkyl, haloalkyl, alkoxy, thioalkoxy, alkoxyalkyl, thioalkoxyalkyl or haloalkoxy, or an acyl residue of formula Ra C (Rb) (R < F) -C (0) - or Ra-C (Rb) (Rd) -C (S) -, where Rb and Rd are selected, independently from each other, from hydrogen or lower alkyl and Ra is -N (Re) (Rf), -ORe or -SRe, where R "and R 'are selected, independently from each other, from hydrogen, lower alkyl and haloalkyl, or an aminacyl residue having the formula R10 NH (CH2 ) 2N HCH2C (O) - or R1O NH (CH2) 2OCH2C (O) -, wherein R101 is hydrogen, lower alkyl, (aryl) alkyl, (cycloalkyl) alkyl, acyl, benzoyl or an a-aminacil group. amino acid esters that are of particular interest are the glycine and lysine esters, however, other amino acid residues, including any of the natural amino acids, can also be used and also including those where the group aminacil is -C ()) CH2NR102R103, wherein R102 and R103 are independently selected from hydrogen and lower alkyl or the group -N R102R103, wherein R102 and R103, taken together, form a heterocyclic ring containing nitrogen. Other prodrugs include a compound of Formula I, II and III substituted with hydroxyl, where the hydroxyl group is functionalized with a substituent of formula -CH (R104) OC (?) R105 or -CH (R10) OC (S) R10S, where R105 is lower alkyl, haloalkyl, alkoxy, thioalkoxy or haloalkoxy and R104 is hydrogen, lower alkyl, haloalkyl, alkoxycarbonyl, amincarbonyl, alkylamincarbonyl or dialkylamincarbonyl. Said prodrugs can be prepared according to the Schreiber process (Tetrahedron Lett 1983, 24, 2363) by ozonolysis of the corresponding methallyl ether in methanol, followed by treatment with acetic anhydride The preparation of the esters of the compounds of Formula I, II and III substituted with hydroxyl is carried out by reacting a compound of Formula I, II and III substituted with hydroxyl, with an aminacil, phosphoryl, hemisuccinyl or activated acyl derivative. Prodrugs of the hydroxyl substituted compounds of the compounds of the invention can also be prepared by alkylation of the hydroxyl-substituted compounds of Formula I, II and III, with (halo) alkyl esters, by transacetalization with bi (alkanoyl) acetals or by condensation of the hydroxyl group with an activated aldehyde followed by acylation of the hemiacetal intermediate. In the preparation of the prodrugs it is often necessary to protect other reactive functional groups in order to prevent unwanted side reactions. After protecting the reactive groups, the desired group can be functionalized. The resulting functionalized product is then deprotected to remove the protective groups that were added to prevent unwanted side reactions. This will provide the desired prodrug. Suitable reaction conditions for the preparation of protecting groups are well known in the art. Said reaction conditions can be consulted in T. H. Greene and P.G. M. Wuts, Protective Groups in Orqanic Svnthesis. 2"edition, John Wiley & Sons, New York (1991). This invention also encompasses compounds of formula I, II and ll which are esters or prodrugs and which are also salts. For example, a compound of the invention can be an ester of a carboxylic acid and also an acid addition salt of a substituent containing amine or nitrogen in the same compound. The compounds of the present invention are useful in the inhibition of neuraminidases of microorganisms that cause diseases that contain a neuraminidase. The compounds of the invention are useful (in humans, other mammals and birds) for the treatment or prevention of diseases caused by microorganisms containing a neuraminidase. The compounds of the present invention are useful in the inhibition of neuraminidase of influenza A virus and neuraminidase of influenza B virus, in vitro or in vivo (especially in mammals and, in particular, in humans). The compounds of the present invention are also useful for the inhibition of influenza viruses, orthomyxoviruses and paramyxoviruses in vivo, especially the inhibition of influenza A viruses and influenza B viruses in humans and other mammals. The compounds of the present invention are also useful in the treatment of infections caused by influenza viruses, orthomyxoviruses and paramyxoviruses, in vivo, especially diseases of humans caused by influenza A and influenza B viruses. of the present invention are also useful for the prophylaxis of infections caused by influenza viruses, orthomyxoviruses and paramyxoviruses, in vivo, in humans and other mammals, especially the prophylaxis of viral infections of influenza A and influenza B, and, in particular, the prophylaxis of viral influenza infections A and influenza B in human subjects who present a high risk of developing other respiratory diseases, who are concurrent or who appear as a result of infections by an influenza virus, or who suffer from a chronic respiratory disease, such as asthma, emphysema or fibrosis quistic The total daily dose administered to a human or other mammalian host, in single or divided doses, may comprise amounts, for example, from 0.001 to 300 mg / kg of body weight per day and more commonly from 0.1 to 10 mg /. kg of body weight per day. The unit dosage compositions may contain submultiples of said amounts to constitute the daily dose.

The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form varies depending on the host treated and the particular mode of administration. It will be understood, however, that the specific dose level for any particular patient will depend on various factors, including the activity of the specific compound employed, age, body weight, general health status, sex, diet, time administration, the administration route, the speed of excretion, the combination of drugs and the severity of the particular disease that is under therapy. Administration of a compound of this invention will begin before or at the time of infection or after the onset of established symptoms and / or confirmation of infection. The compounds of the present invention can be administered orally, parenterally, sublingually, intranasally, by intrapulmonary administration, by inhalation or insufflation as a solution, suspension or dry powder (for example, in a spray) or rectally, in formulations of unit dosage containing conventional vehicles, adjuvants and non-toxic transporters, acceptable for pharmaceutical use, according to need. The term parenteral, as used herein, includes subcutaneous, intravenous, intramuscular, intrasternal or infusion techniques.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art, wetting or dispersing agents and suitable suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic diluent or solvent acceptable for parenteral use, for example, as a solution in 1,3-propanediol. Among the acceptable vehicles and solvents that may be employed, the following may be mentioned: water, Ringer's solution and isotonic sodium chloride solution. In addition, fixed oils are conventionally used sterile as a solvent or suspension medium For this purpose, any inert fixed oil, including synthetic mono- or diglycerides, can be used. In addition, fatty acids, such as oleic acid, are useful in the preparation of injectables. Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient, such as cocoa butter and polyethylene glycols, which is solid at ordinary temperatures but liquid at rectal temperature and will therefore dissolve in the rectum. and will release the drug. Solid dosage forms for oral administration may include capsules, tablets, pills, powders and granules. In said solid dosage forms, the active compound may be mixed with at least one inert diluent, such as sucrose. , lactose or starch. Said dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, for example, lubricating agents, such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise regulatory agents. Tablets and pills can also be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing the inert diluents commonly used in the art, such as Water Said compositions may also comprise adjuvants, such as wetting agents, emulsifiers and suspending agents, and sweetening, sabotating and perfuming agents. The compounds of the present invention may also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. The liposomes are formed by liquid mono- or multilamellar hydrated crystals that are dispersed in an aqueous medium. Any non-toxic lipid can be used., physiologically acceptable and metabolizable able to form liposomes. The present compositions in the form of liposomes may contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. Preferred lipids are phospholipids and phosphatidylcholines (lecithins), both natural and synthetic. Methods for forming liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Bioloqy, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 and next While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more anti-infective agents and / or other agents used to treat other acute or chronic respiratory conditions. Other agents that can be administered in combination with a compound of the present invention include: a vaccine against influenza; other influenza inhibitors such as, for example, amantadine, pmantadine, ribavirin and the like; other inhibitors of influenza neuraminidases, such as, for example, zanamivir or GS 4104 and the like; the agents used to treat bacterial respiratory infections and bronchitis, such as, for example, erythromycin, clarithromycin, azithromycin and the like; and agents used to treat asthma, such as, for example, zileuton, albuterol (salbutamol), salmeterol, formoterol, ipratropium bromide, inhaled steroids and the like, or anti-inflammatory agents for the treatment of asthma such as, for example, beclomethasone dipropionate, fluticasone propionate, budesonide, triamcinolone acetonide, flunisolide, cromolyn, zafirlukast, montelukast, used in combination with a compound of the present invention. When administered as a combination, the therapeutic agents can be formulated as separate compositions that are administered at the same time or at different times, or the therapeutic agents can be administered as a single composition. The above description is only illustrative of the invention and is not intended to limit the invention to the disclosed compounds. It is intended to include the variations and changes that are obvious to those skilled in the art in the scope and nature of the invention as defined in the appended claims.

Claims (56)

1. A compound that has the Formula

   or a salt, an ester or an acceptable prodrug for pharmaceutical use thereof, wherein R1 is selected from the group consisting of (a) -C? 2H, (b) -CH2C? 2H, (c) -S03H, (d) - CH2S?, H, (e) -S? 2H,

   (f) -CH2S02H, (g) -P? 3H2, (h) -CH2P03H2, (i) -P? 2H, 0) -CH2P? 2H, (k) tetrazolyl, (I) -CH2-tetrazolyl, (m) ) -C (= 0) -NH-S (?) 2 -R11,

   (n) -CH2C (= 0) -N HS (0) 2-R11, (o) -S02N (T-R11) R12 and (p) -CH2S02N (T- where T is selected from the group consisting of (i) a bond, (ii) -C (=?) -, (iii) -C (=?)? -, (iv) -C (=?) S-, (v) -C (?) NR36, (vi) ) -C (= S)? -, (vii) -C (= S) S- and (viii) -C (= S) N R36-, R11 is selected from the group consisting of (i) C? -C12- alkyl, (ii) C2-C2-alkenyl, (iii) cycloalkyl, (iv) (cycloalkyl) alkyl, (v) (cycloalkyl) alkenyl, (vi) cycloalkenyl, (vii)

   (cycloalkenyl) alkyl, (viii) (cycloalkenyl) alkenyl, (ix) aryl, (x)

   (aryl) alkyl, (xi) (aryl) alkenyl, (xii) heterocyclic, (xiii)

   alkyl (heterocyclic) and (xiii) (xiv) alkenyl (heterocyclic); and R12 and R36 are independently selected from the group consisting of (i) hydrogen, (ii) (iii) C2-C2-alkenyl, (iv) cycloalkyl, (v) (cycloalkyl) alkyl, ( vi) (cycloalkyl) alkenyl, (vii) cycloalkenyl, (viii) (cycloalkenyl) alkyl, (ix)

   (cycloalkenyl) alkenyl, (x) aryl, (xi) (aryl) alkyl, (xii) (aryl) alkenyl, (xiii) heterocyclic, (xiv) alkyl (heterocyclic) and (xv) alkenyl (cyclic hetero); X is selected from the group consisting of (a) -C (=?) - N (R ") -, (b) - N (R") - C (= 0) -, (c) -C (= S) -N (R>, (d) -N (R ') - C (= S) -, (e) -N (R') - S02-, and M -S? 2-N (R ") - wherein R 'is hydrogen, Ct-Cs-lower alkyl or cyclopropyl, R2 is selected from the group consisting of (a) hydrogen, (b) C? -C6-alkyl, (C) C2-C6-alkenyl, (d) C3-C6-cycloalkyl, (e) C5-C6-cycloalkenyl, (f) halo-C? -C6-alkyl and (g) halo-C2-C6-alkenyl; or R2-X is

   where Y1 is -CH2-, -S- or -N H- and Y2 is -C (= 0) - or -C (Raa) (Rbb), where Raa and Rbb are selected, independently from each other, from the group formed by hydrogen, C? -C3-lower alkyl,

   hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminomethyl, thiolmethyl, 1-thiolethyl, 2-thioletyl, methoxymethyl, N-methylaminomethyl and methylthiomethyl; R3 and R4 are independently selected from the group consisting of (a) hydrogen, (b) cycloalkyl, (c) cycloalkenyl, (d) heterocyclic, (e) aryl and (f) -Z-R14 where Z is ( i) -C (R37a) (R37b) -, (ii) -C (R47) = C (R46) -, (iii) -CsC-, (iv) -C (= 0) - (v) -C ( = S) -, (vi) -C (= NR 15) -, (vii) -C (R37a) (OR37c) -, (viii) -C (R37a) (SR37c) -, (ix) -C (R37a) ) (N (R37b) (R37c)) -, (x) -C (R37a) (R37b) -0-, (xi) -C (R37a) (R37b) -N (R37c) -, (xii) -C (R37a) (R37b) -N (0) (R37c), (xiii) -C (R37a) (R37b) -N (? H) -, (xiv) -C (R37a) (R37b) -S-, ( xv) -C (R37a) (R37b) -S (?) -, (xvi) -C (R37a) (R37b) -S (?) 2-, (xvii) -C (R37a) (R37b) -C ( =?) -, (xviii) -C (R37a) (R37b) -C (= S) -, (xix) -C (R37a) (R37b) -C (= N R'5) -, (xx) C (R37a) (0R37c) -C (= 0) -, (xxi) -C (R37") (SR37b) -C (=?) -, (xxii) C (R37a) (OR37c) -C (= S) -, (xxiii) -C (R37a) (SR37c) -C (= S) -, (xxiv) -C (= 0) -C (R37a) (? R37c) -, (xxv) -C (= 0) -C (R37a) (SR37c) -, (xxvi) -C (= S) -C (R37a) (? R37c) -, (xxvii) -C (= S) -C (R37a) (SR37c) -, ( xxviii) C (R37a) (? R37c) -C (R37a) (? R37c) -, (xxix) -C (R7a) (SR37c) -C (R3 a) (0R370) -, (xxx) -C ( R3 7a) (? R37o) -C (R37a) (SR37c) -, (xxxi) -C (R37a) (SR37c) -C (R37a) (SR37c) -, (xxxii) -C (=?) - C (= ?) -, (xxxiii) -C (= S) -C (= S) -, (xxxiv) -C (= 0) -0-, (xxxv) -C (=?) - S-, (xxxvi) -C (= S) -0-, (xxxvii) -C (= S) -S-, (xxxviii) -C (=?) - N (R37a) - (xxxix) -C (= S) -N ( R 7a) -, (xl) -C (R37a) (R37b) -C (=?) - N (R37a) -, (xli) -C (R37a) (R37b) -C (= S) -N (R37a ) -, (xlii)

   C (R37a) (R37b) -C (= 0) -0-, (xliii) -C (R37a) (R37b) -C (= 0) -S-, (xliv) C (R37a) (R37) -C (= S) -0-, (xlv) -C (R37a) (R37b) -C (= S) -S-, (xlvi) C (R37a) (R37b) -N (R37b) -C (= 0) -, (xlvii) -C (R37a) (R37b) -N (R37b) -C (= S) -, (xlviii) -C (R37a) (R37b) -0-C (=?) -, (xlix) -C (R37a) (R37b) -SC (=?) -, (I) -C (R37a) (R37b) -0-C (= S) - (M) C (R37a) (R37b) -SC (= S) -, (Ni)

   C (R37a) (R37b) -N (R37b) -C (= 0) -N (R37a) -, (liii) -C (R37a) (R37b) -N (R37b) -C (= S) -N ( R37a) -, (liv) -C (R37a) (R37b) -N (R37b) -C (=?) -? -, (Iv) C (R37a) (R37b) -N (R37b) -C (= 0) -S-, (Ivi) -C (R37a) (R37) -N (R37b) -C (= S) -0 -, (Ivii) -C (R37a) (R37b) -N (R37b) -C (= S) -S-, (Iviii) -C (R37a) (R37b) -0-C (=?) - N ( R37a) -, (lix) -C (R37a) (R37b) -SC (= 0) -N (R37a) -, (Ix) -C (R37a) (R37b) -0-C (= S) -N ( R37a) -, (Ixi) -C (R37a) (R37b) -SC (= S) -N (R37a) -, (Ixii) C (R37a) (R37b) -0-C (= 0) -0-, (Ixiii) -C (R37a) (R37b) -SC (=?) - 0-, (Ixiv) -C (R37a) (R37) -? - C (=?) - S-, (Ixv) -C ( R37a) (R37b) -SC (=?) -S-, (Ixvi) -C (R37a) (R37b) -0-C (= S) -0-, (Ixvii) -C (R37a) (R37b) - SC (= S) -? -, (Ixviii) -C (R37a) (R37b) -? - C (= S) -S-, (Ixix) -C (R37a) (R37b) -SC (= S) - S- or (Ixx) -C (R37a) (R37b) -C (R37a) (OR37c) -; R '4 is (i) hydrogen, (ii) C? -C, 2-alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) thiol-substituted alkyl, (vi) R37c-0-substituted alkyl, ( vii) alkyl R37c-S-substituted, (viii) aminoalkyl, (ix) alkyl (R37c) NH-substituted, (x) alkyl (R37a) (R37c) N-substituted, (xi) alkyl R37aO - (? =) C -substituted, (xii) alkyl R37a-S - (? =) C-substituted, (xiii) alkyl R37a? - (S =) C-substituted, (xiv) alkyl R37a-S- (S =) C-substituted, (xv) alkyl (R37a?) 2-P (=?) - substituted, (xvi) cyanoalkyl, (xvi) C2-C? 2-alkenyl, (xviii) haloalkenyl, (xix) C2-C? 2-alkynyl,

   (xx) cycloalkyl, (xxi) (cycloalkyl) alkyl, (xxii) (cycloalkyl) alkenyl, (xxiii) (cycloalkyl) alkynyl, (xxiv) cycloalkenyl, (xxv)

   (cycloalkenyl) alkyl, (xxvi) (cycloalkenyl) alkenyl, (xxvii)

   (cycloalkenyl) alkynyl, (xxviii) aryl, (xxix) (aryl) alkyl, (xxx) (aryl) alkenyl, (xxxi) (aryl) alkynyl, (xxxii) heterocyclic, (xxxiii) alkyl (heterocyclic), (xxxiv) alkenyl (heterocyclic) or (xxxv) (heterocyclic) alkyne or lo, with the proviso that R14 is other than hydrogen when Z is -C (R37") (R37b) -N (R37b) -C (= 0) - ? -, -C (R37a) (R37b) -N (R37b) -C (= S) -? -, -C (R37a) (R37b) -N (R37b) -C (= 0) -0-, - C (R37a) (R37b) -N (R37b) -C (= S) -S-, -C (R37a) (R37b) -0-C (= 0) -0-, -C (R37a) (R37b) -0-C (= S) -? -, -C (R37a) (R37b) -SC (= 0) -0-, -C (R37a) (R37b) -SC (= S) -0-, -C (R37a) (R37b) -0-C (= 0) -S-, -C (R37a) (R37b) -0-C (= S) -S-, -C (R37a) (R37b) -SC (= 0) -S or -C (R37a) R37) -SC (= S) -S-, R37, R37b and R37c, are selected at each occurrence, independently of each other, from the group consisting of (i) hydrogen, (ii) C, -C2-alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) alkoxyalkyl, (vi) C2-C2-alkenyl, (vii) haloalkenyl, (viii) C2-C12-alkynyl, (vi) ix) cycloalkyl, (x) (cycloalkyl) alkyl, (xi) (cycloalkyl) alkyl uenil, (xii)

   (cycloalkyl) alkynyl, (xiii) cycloalkenyl, (xiv) (cycloalkenyl) alkyl, (xv) (cycloalkenyl) alkenyl, (xvi) (cycloalkenyl) alkynyl, (xvii) aryl, (xviii) (aryl) alkyl, (xix) (aryl) alkenyl, (xx) (aryl) alkynyl, (xxi) heterocyclic, (xxii) alkyl (heterocyclic), (xxiii) alkenyl (heterocyclic) and (xxiv) alkynyl (heterocyclic),

   R37c is selected at each occurrence, independently, from the group consisting of (i) hydrogen, (ii) C? -C? 2-alkyl, (iii) haloalkyl, (iv) C2-C? 2-alkenyl, (v) haloalkenyl, (vi) C2-C12-alkynyl, (vii) cycloalkyl, (viii) (cycloalkyl) alkyl, (ix) (cycloalkyl) alkenyl, (x)

   (cycloalkyl) alkynyl, (xi) cycloalkenyl, (xii) (cycloalkenyl) alkyl, (xiii) (cycloalkenyl) alkenyl, (xiv) (cycloalkenyl) alkynyl, (xv) aryl, (xvi) (aryl) alkyl, (xvii) (aryl) alkenyl, (xviii) (aryl) alkynyl, (xix) heterocyclic, (xx) alkyl (heterocyclic), (xxi) alkenyl (heterocyclic), (xxi i) alkynyl (heterocyclic), (xxiii) -C ( = 0) -R14, (xxiv) -C (= S) -R, (xxv) -S (0) 2 -R'4 and (xxvi) hydroxyalkyl; or when Z is -C (R37a) (R37b) -N (R3 c) -, then when N (R37c) and R14 are taken together they constitute an azide group; or when Z is -C (R37a) (R37) -N (?) (R37c) -, then when N (?) (R37c) and R14 are taken together they constitute an N-oxidized 3-7 membered heterocyclic ring possessing at least one nitrogen atom in the N-oxidized ring, or when Z is -C (R37a) (0R37c) -, -C (R37a) (SR37c) - or -C (R37a) (N (R37b) (R37c) )) -, then R37a, R14 and the carbon atoms to which they are attached when taken together form a cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl ring; R15 is selected from the group consisting of (i) hydrogen, (ii) hydroxy, (iii) amino, (iv) C? -C? 2 -alkyl, (v) haloalkyl, (vi) C2-C? 2- alkenyl, (vii) haloalkenyl, (viii) cycloalkyl, (ix) (cycloalkyl) alkyl, (x) (cycloalkyl) alkenyl, (xi)

   cycloalkenyl, (xii) (cycloalkenyl) alkyl, (xiii)

   (cycloalkenyl) alkenyl, (xiv) aryl, (xv) (aryl) alkyl, (xvi) (aryl) alkenyl, (xvii) heterocyclic, (xviii) alkyl (heterocyclic) and (xix) alkenyl (heterocyclic), or R3 and R4 taken together, with the atom to which they are attached, form a carbocyclic or heterocyclic ring possessing 3 to 8 ring atoms, R5 is selected from the group consisting of (a) hydrogen, (b) -CH (R3a) 2 , (c) -O-R40, (d) C2-C "-alkyl, (e) cyclopropyl, cyclobutyl, (g) -C (= Q ') - R17 and (h) -N (R,) 2 where Q 'is O, S or N (R18); R 17 and R 8 are independently selected, at each occurrence, from the group consisting of hydrogen, methyl and ethyl; R 9, R 38 and R 40 are selected from the group consisting of (i) hydrogen, (ii) (iii) haloalkyl, (iv) C2-C? 2-alkenyl, (v) haloalkenyl, (vi) cycloalkyl, (vii) ) (cycloalkyl) alkyl, (viii) (cycloalkyl) alkenyl, (ix) cycloalkenyl, (x)

   (Cycloalkenyl) alkyl, (xi) (cycloalkenyl) alkenyl, (xii) aryl, (xiii) (aryl) alkyl, (xiv) (aryl) alkenyl, (xv) heterocyclic, (xvi) alkyl (heterocyclic) and (xvii) alkenyl (heterocyclic); Y is selected from the group consisting of (a) hydrogen, (b) C? -C < -alkyl, (c) C? -C3 -haloalkyl, (d) C2-Cs-alkenyl, (e) C2-C5-haloalkenyl, (f) C2-C5-alkynyl, (g) C3-C5-cycloalkyl, (h) C3-C5-cycloalkyl-C? -a-C3-alkyl, (i) C5-

   cycloalkenyl, (j) C5-cycloalkenyl-C? -a-C3-alkyl, (k) C5-cycloalkenyl-C2-a-C3-alkenyl, (I) - (CHR3) "OR2 °, (m) -CH ( OR20) -CH2 (OR20), (n) - (CHR39) nSR21, (o) - (CHR39) "CN, (p) - (CHR39) N3, (q) phenyl, (r) halo-substituted phenyl, ( s) - (CHR39) "C (= Q2) R22, (t) - (CHR39) nN (= Q3), (u) -N (?) = CHCH3, (v) - (CHR3)" NR 3R24, ( w) halo and (x) a heterocyclic ring having 3 to 6 ring atoms; where the value of n is 0, 1 or 2; Q2 is O, S, NR or CHR; and Q3 is NR41 or CHR42; in each occurrence R20 is independently

   (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) C? -C3-haloalkyl, (vii) vinyl, (viii) propenyl, (ix) isopropenyl, (x) allyl, (xi) C2-C3-haloalkenyl, (xii) amino, (xiii) -NHCH3, (xiv) -N (CH3) 2, (xv) -NHCH2CH3, (xvi) -N (CH3 ) (CH2CH3), (xvii) -N (CH2CH3) 2 or (xviii) -N (= CH2); R21 is (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl,

   (vi) C? -C3-haloalkyl, (vii) vinyl, (viii) propenyl, (ix) isopropenyl, (x) allyl or (xi) C2-C3-haloalkenyl; R22 is (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) hydroxy, (vii) thiol, (viii) methoxy, (ix) ethoxy, ( x) n-propoxy, (xi) isopropoxy, (xii) cyclopropyloxy, (xiii) methylthio, (xiv) ethylthio, (xv) n-propylthio, (xvi) isopropylthio, (xvii) cyclopropylthio, (xviii) vinyl, (xix ) propenyl, (xx) isopropenyl, (xxi) allyl, (xxii) -N (R28a) (R28b), (xxiii) -CH2R29, (xxiv) aminomethyl, (xxv) hydroxymethyl, (xxvi) tiolmetilo, (xxvii) - NHNH2, (xxviii) -N (CH3) NH2 or (xxix) -NHNH (CH3);

   R23 and R39 are, independently of each other, hydrogen or methyl, R41 and R42 are, independently of each other, hydrogen, methyl or ethyl, R24 is selected from the group consisting of (i) hydrogen, (ii) Ci-C-alkyl, ( iii) C2-C4-alkenyl, (iv) C2-C4-alkynyl, (v) cyclopropyl, (vi) -C (= Q4) -R30, (v) -OR31 and (vi) -N (R32) 2, where Q4 is O, S or N (R33); R25 is hydrogen, hydroxy, methyl, ethyl, amino, -CN or -N02; The group R26 is hydrogen, methyl or ethyl; R28a is hydrogen, hydroxy, methyl, ethyl, amino, -N HCH3, -N (CH3) 2, methoxy, ethoxy or -CN; R28b is hydrogen, methyl or ethyl, or, R28a, R28b and nil together represent azetidinyl; the group R29 is hydrogen, hydroxy, thiol, methyl, ethyl, amino, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino; the group R30 is hydrogen, methyl, ethyl, -OR34, -SR34, -N (R35) 2, -NHOH, -N H N H2, -N (CH3) N H2 or -N (CH2CH3) N H2; the substituents R31 and R32, at each occurrence, are, independently of each other, hydrogen, methyl or ethyl; the R33 group is hydrogen, hydroxy, methyl, ethyl, amino, -CN or -N? 2; the group R34 is methyl or ethyl; the group R 35 is, independently, hydrogen, methyl or ethyl; with the proviso that when Q2 is CHR26 then R22 is

   selected from the group consisting of hydrogen, -CH3, -C2H5, -C3H7, -OCH3, -SCH3, -0-C2Hs and -S-C2H5, and with the proviso that when R3 and R4 are, each, hydrogen, then And it's different from hydrogen; R6 and R7 are independently selected from the group consisting of (a) hydrogen, (b) C? -C? 2-alkyl, (c) C2-C? 2-alkenyl, (d) cycloalkyl, ( e) (cycloalkyl) alkyl, (f) (cycloalkyl) alkenyl, (g) cycloalkenyl, (h) (cycloalkenyl) alkyl, (i) (uenil cycloalk) alkenyl, (j) aplo, (k) (p l) alk α, (I) (aryl) alkenyl, (m) heterocyclic, (n) alkyl (heterocyclic) and (o) alkenyl (heterocyclic); and R8, R9 and R1 ° are independently selected from the group consisting of (a) hydrogen, (b) C? -C6-alkyl, (C) C2-C6-alkenyl, (d) C3-C6-cycloalkyl , (e) C3-C6-c-chloralkenyl, and (f) fluorine, with the proviso that the total amount of atoms, other than hydrogen, in each of R8, R9 and R10, is 6 atoms or less.
2. 2. The compound according to claim 1 having the relative stereochemistry represented in the Formula:

   where R1, R2R3, R4, Rs, R5, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal.
3. 3. The compound according to claim 1 having the relative stereochemistry represented in the Formula:

   defined above and where R3 and R4 are not equal.
4. 4. The compound according to claim 1, wherein: -X-R2 is R2-C (= 0) -NH-, R2-N HC (=?) -, R2-NH-S02- or R2-S02 -N H-, where R2 is C? -C3-lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C2-C3-alkenyl or -X-R2 is

   -y O »- where Y1 -CH2 -NH- -C (=?) - or

   and £.-y.

   -C (Raa) (Rbb) -, where Raa and Rbb are independently selected from the group consisting of hydrogen, d-C3-lower alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, thiolmethyl, 1-thiolethyl, 2-thiolethyl, methoxymethyl, N-methylamino nomethyl and methylthiomethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, wherein Z and R14 are as defined above and wherein one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl: R5 and R7 are, independently of each other, hydrogen or lower alkyl; R8 and R9 are, independently of each other, hydrogen, fluorine or lower alkyl; R10 is hydrogen, fluorine or lower alkyl; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (0) = CHCH3, -N R23R24 or a heterocyclic ring possessing 3 to 6 atoms in the ring, where R22, R23, R24, Q2 and Q3 are as defined above.
5. 5. The compound according to claim 4 having the relative stereochemistry represented in the Formula:

   where R1, R2R3, R4, R5, R6, R7, R8, R9, R0, X and Y have the values as defined above and where R3 and R4 are not equal 6. The compound according to claim 4 which has the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal.

   7. The compound according to claim 1, wherein -X-R2 is R2-C (= 0) -NH-, R -NH-C (=?) -, R2-N H-S02- or R2-S02- N H-, where R2 is C? -C3-lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C2-C3-alkenyl or -X-R2 is

   where Y1 is -CH2- and Y2 is -C (= 0) - or -C (Raa) (Rbb), where Raa and Rb are independently selected from the group consisting of hydrogen, C? -C3-alkyl lower, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, where Z and R4 are as defined above and where one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl; R6 and R7 are, independently of each other, hydrogen or lower alkyl; R8 and R9 are, independently of each other, hydrogen or lower alkyl; R 10 is hydrogen or lower alkyl, and Y is C2-C5-alkenyl, C2-C3-haloalkenyl, -C (= Q2) R22, -N (= Q3), -N (?) = CHCH3 or a heterocyclic ring which It has 5 atoms in the ring and it also contains one or two double bonds, where R22, Q2 and Q3 are as defined above. 8. The compound according to claim 7 having the relative stereochemistry represented in the Formula:

   where R, R2 R3, R4, R J R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal. 9. The compound according to claim 7 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal. 10. A compound according to claim 1 wherein -X-R2 is R2-C (=?) - N H-, R2-N HC (= 0) -, R2-N HS? 2- or R -S02 -N H-, where R2 is C? -C3-lower alkyl, halo C? -C3-lower alkyl, C2-C3-alkenyl or halo C? -C3-alkenyl or -X-R2 is

   where Y1 is -CH2- and Y2 is -C (= 0) - or -C (Raa) (Rbb), where Raa and Rbb are independently selected from the group consisting of hydrogen, C? -C3-lower alkyl , hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl; R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, wherein Z and R14 are as defined above and wherein one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl; R6 and R7 are, independently of each other, hydrogen or lower alkyl; R8 and R9 are, independently of each other, hydrogen or lower alkyl; R 0 is hydrogen or lower alkyl; and Y is C2-C5-alkenyl, C2-C3-haloalkenyl or a heterocyclic ring with 5 ring atoms and also containing one or two double bonds. 1 1. The compound according to claim 10 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R1, X and Y have the values defined above and where R3 and R4 are not equal. 12. The compound according to claim 10 having the relative stereochemistry represented in the Formula:

   where R \ R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal.

   13. A compound according to claim 1 wherein: R1 is -C? 2H-, -X-R2 is R2-C (=?) - N- H-, R -N HC (=?) -, R2-N HS ? 2- or R2-S? 2-NH-, where R2 is C, -C3-lower alkyl or halo-C? -C3-lower alkyl,

   R3 and R4 are independently selected from hydrogen, heterocyclic and -Z-R14, where Z and R4 have the values defined above and where one of R3 and R4 is other than hydrogen; R5 is hydrogen or lower alkyl; R6 and R7 are independently hydrogen or lower alkyl; R8 and R9 are independently hydrogen or lower alkyl; R10 is hydrogen or lower alkyl; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 atoms in the ring and also containing one or two double bonds. 14. The compound according to claim 13 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal. 15. The compound according to claim 13 having the relative stereochemistry represented in the Formula:

   where R, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal. 16. The compound according to claim 1 wherein

   R 1 is -C02H; -X-R2 is R2-C (= 0) -N H-, R2-N HC (= 0) -, R2-N H-S02- or R2-S02-N H-, where R2 is C, -C3 lower alkyl or halo-C? -C3-lower alkyl;

   R 4 is hydrogen or lower alkyl and R 3 is heterocyclic or -Z-R 14, wherein Z and R 14 are as defined above; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R10 is hydrogen; and Y is C2-C5-alkenyl, C2-C3-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. 17. The compound according to claim 16 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R1, X and Y have the values defined above and where R3 and R4 are not equal.

   18. The compound according to claim 16 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R °, X and Y have the values defined above and where R3 and R4 are not equal. 19. The compound according to claim 1, wherein R1 is -C02H; -X-R2 is R2-C (=?) - N H-, R2-NH-C (=?) -, R2-N HS? 2- or R2-S? 2-N H-, where R2 is C C3-lower alkyl or halo Ci-C-lower alkyl;

   R4 is hydrogen or lower alkyl and R3 is (a) heterocyclic, (b)

   alkyl, (b) cycloalkyl, (d) cycloalkylalkyl, (e) alkenyl, (f) alkynyl, (g) -C (= 0) -R14, (h) -C (R37a) (OR37c) -R14 or (i) ) -C (R37a) (R37b) -cycloalkylalkyl, (iv) alkenyl, (v) haloalkyl, (vi) haloalkenyl, (vii) aryl, (viii) arylalkyl, (ix) heterocyclic, (x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xii) alkoxyalkyl, (xiii) cyanoalkyl, (xiv) alkyl (R37a0) - (0 =) C-substituted or (xv) alkyl (R37aO) 2-P (= 0) -substituted; R37a and R37b are independently separated from each other, from the group consisting of (i) hydrogen, (ii) lower alkyl and (iii) lower alkenyl; and R37c is hydrogen, (ii) lower alkyl or (iii) lower alkenyl; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R10 is hydrogen; and Y is C2-Cs-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. The compound according to claim 19, having the relative stereochemistry represented in the Formula:

   where R, R2, R3, R4, Rs, R6, R7, R8, R9, R10, X and Y have the values that were previously defined and where R3 and R4 are not equal.

   twenty-one . The compound according to claim 19 having the relative stereochemistry represented in the Formula.

   defined above and where R3 and R4 are not equal. 22. The compound according to claim 1, wherein R1 is -C? 2H; -X-R2 is R2-C (= 0) -NH-, R -NH-C (=?) -, R2-NH-S02- or R2-S02-NH-, where R2 is C? -C3-alkyl lower or halo C? -C3-lower alkyl;

   R4 is hydrogen and R3 is (a) heterocyclic, (b) alkyl or (c) -

   C (R37a) (OR37c) -R14, wherein R14 is (i) alkyl, (h) cycloalkyl, (ili) cycloalkylalkyl, (iv) alkenyl,

   (v) haloalkyl, (vi) haloalkenyl, (vii) aryl, (viii) aplakyl, (ix) heterocyclic, (x) alkyl (heterocyclic), (xi) hydroxyalkyl, (xii) alkoxyalkyl, (xiii) cyanoalkyl, (xiv) alkyl (R37aO) - (0 =) C-substituted or (xv) alkyl (R37a?) 2-P (=?) - substituted; R37a and R37b are independently selected from the group consisting of (i) hydrogen, (ii) lower alkyl and (iii) lower alkenyl; and R37c is (i) hydrogen, (ii) C? -C3-lower alkyl or (iii) allyl; R5 is hydrogen; R6 and R7 are hydrogen, R1 and R9 are hydrogen R10 is hydrogen; and Y is C2-Cs-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. 23. The compound according to claim 22, having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R3, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not identical. 24. The compound according to claim 22 having the relative stereochemistry represented in the Formula:

   where R \ R2, RJ, R4, R5 R ', R °, Rs, R10, X and Y have the values

   25. The compound according to claim 1, wherein R1 is -C02H, -X-R2 is R2-C (=?) - N H- or R2-S02-N H-, where R2 is C1-C3-lower alkyl or halo C? -C3-lower alkyl; R4 is hydrogen and R3 is (a) heterocyclic, (b) alkyl or (c) -C (R37a) (OR37c) -R14 where R14 is (i) lower alkyl, (ii) lower alkenyl, (iii) lower alkyl hydroxy -substituted or (iv) lower alkoxy-substituted alkyl; R37a is (i) hydrogen, (ii) lower alkyl or (iii) lower alkenyl; Y

   R37c is

   (i) hydrogen, (ii) C? -C3-lower alkyl or (iii) allyl; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R10 is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. 26. The compound according to claim 25, having the relative stereochemistry represented in the Formula -

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values that were previously defined and where R3 and R4 are not equal. 27. The compound according to claim 25 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal. 28. The compound according to claim 1, wherein R1 is -C02H; -X-R2 is R2-C (= 0) -NH- or R2-S02-NH-, where R2 is C, -C3-lower alkyl or halo C? -C3-lower alkyl: R4 is hydrogen and R3 is - C (R37a) (OR37c) -R14, wherein R 4 is lower alkyl or lower alkenyl; R37a is lower alkyl or lower alkenyl; and R37c is hydrogen, Ci-Ca-lower alkyl or allyl; R5 is hydrogen; R6 and R7 are hydrogen; R8 and R9 are hydrogen; R10 is hydrogen; and Y is C2-C5-alkenyl, C2-C5-haloalkenyl or a heterocyclic ring having 5 ring atoms and also containing one or two double bonds. 29. The compound according to claim 28 which

   has the relative stereochemistry represented in the Formula

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X and Y have the values defined above and where R3 and R4 are not equal.

   30. The compound according to claim 29 having the relative stereochemistry represented in the Formula:

   where R1, R2, R3, R4, R5, R6, R7, R8, R9, R1 °, X and Y have the values defined above and where R3 and R4 are not equal. 31. A compound selected from the group consisting of: Acid (±) - (2R, 3S, 5R, 1 'R) -2- (1-Acetamido-2-ethyl-2-hydroxy) butyl-3- (cis- propen-1-yl) -pyrrolidine-5-carboxylic acid; Acid (±) - (2R, 3S, 5R, 1 'R, 2'S) -2- (1-Acetamido-2-hydroxy-2-methyl) pentyl-3- (cis-propen-1-yl) -pyrrolidin- 5-carboxylic;

   Acid (±) - (2R, 3S, 5R, 1"R, 2'S) -2- (1-acetamido-2-et? L-2-hydrox?) Pent? L-3- (c? s-propen-1-? l) -pyrrolidone-5-carboxylic acid (±) - (2R, 3S, 5R 1 'R, 2'S) -2- (1-acetam? do-2-hydrox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxylic acid, tpfluoroacetic salt, acid (±) - (2R, 3R, 5R, 1'R, 2'R) -2- (1-acetamido-2,3-d? H? Drox?) Prop? L-3- (c? S-propen- 1-?) -pyrrolidone-5-carboxylic acid (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-Acetamido-2) -h? drox? -4-v? n? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, ( -) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-2-et? L) but? L-3- (c? S-propen-1-? L) -p? Rrol ? d? n-5-carbox? lato ammonium salt Acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetam? do-2,3-d? methox) ?) prop? l-3- (b? -propen-1-? l) -p? rrol? d? n-5-carbox? l? co Acid (±) - (2 R, 3S, 5R, r R , 2'S) -2- (1 -aceta m? Do-2-methox? -2-v? N? L) et? L-3- (c? S-propen-1-? L) -p? Rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-acetam? do-2-et? l) but? l-3- (c? s -propen-1-? l) -pyrrolidone-5-carboxylic acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido- 2- (N-? Soprop? LN-met? Lam? NN-ox? Do)) et? L- 3- (c? S-propen-1-? L) -p? Rrol? D? N-5-ca rboxí lico,

   Acid (±) - (2R, 3S, 5R, rS, 3'S) -2- (1-acetamido-2- (N-et? LN-met? Lam? NN-ox? Do)) et? L- 3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox?) But? L-3- (c? S-propen-1? ) -pyrrolidone-5-carboxylic acid, Acid (±) - (2 R, 3S, 5R, 1 'R, 2'S) -2- (1 -acetamido-2-methox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3R, 5R, 1'R , 2"S) -2- (1-acetamido-2-hydrox?) But? L-3-

   (p? razol-3-? l) -p? rrol? d? n-5-carbox? l? co, Acido (+) - (2R, 3S, 5R, 1'R, 2'S) -2- (1 -acetam? do-2-hydrox?) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (± ) - (2R, 3S, 5R, 1'R 2'R) -2- (1-acetamido-1- (3,6-d? H? Dro-2-Hp? Rano-2-? L) ) prop? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -2-al? Lo) et? L-3- (c? S- propen-1-? l) -pyrrolidone-5-carboxylic acid, acid (±) - (2R, 3S, 5R, 1'R, 2"S, 3'S) -2- ( 1-acetamido-2-hydrox-3-metho1) ent-1-3- (cs-propen-1-? L) -pyrrolidone-5-carbox ? l, Acid (±) - (2R 3S.5R 1'R 2'S) -2- (1-acetamido-2-methox? -4-v? n? l) but? l-3- ( c? s-propen-1-? l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- ( 1-Acetamido-2-hydrox-3-cyanine) propyl-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? lcole, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-1- (3,6-d? h? dro-2-Hp? rano -2-? L)) met? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2,3-d? Methox?) Prop? L-3- (c? S-propen- 1-? L) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido- 2-h? Drox? Met? L-2-h? Drox?) Pent? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-ethoxy?) pent? l-3- (c? s-propen-1- (l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-h? drox? -3-d? met? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - ( 2R, 3S, 5R, 1'R, 2"S) -2- (1-acetamido-2-ethoxy? -3-v? N? L) prop? L-3- (c? S-propen- 1-? L) -p? Rrol? D? N-5-carboxyl? Co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox? -2- (propen-2-? L)) et? L- 3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) - 2- (1-acetam-2-hydrox?) Hex? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co , Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-met? L) but? L-3- (c? S-propen-1-? L) - pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox? ) but? l-3-v? n? lp? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1 -acetam) id o-2-h id rox?) pent? l-3-v? n? lp? rrol? d? n-5-carbox? l? co Acid (±) - (2R, 3S, 5R, 1'R , 2'R) -2- (1-acetamido-2-hydrox? Et? L-2-hydrox?) Pent? L-3- (c? S-propen-1-? L) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2"R) -2- (1-acetamido-2-hydrox?) But? L-3-v? N? Lp? r? r? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1"R, 2'R) -2- (1-acetam? do-2-methox?) pent? l -3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carbox? L? Co, Acid (±) - (2R, 3S, 5R, 1'R, 2 ' R) -2- (1-acetamido-2-hydroxy) pent? L-3-v? N? Lp? Rrol? D? N-5-carboxyl? Co, Acid (±) - (2R) , 3S, 5R, 1"R) -2- (1-acetamido-2-hydrox?) Et? L-3- (c? S-propen-1-yl) -p? Rrol? D? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-Acetam? do-3-met? l) but? l-3- (c? s-2) -cloro-v? n-1-? l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido) -3-met? L) but? L-3- (p? Razol-3-? L) -p? Rrol? D? N-5-carboxyl? Co, Acid (±) - (2R, 3S, 5R, 1'S, 3'R) -2- (1-acetamido-3-hydrox?) Pent? L-3-

   (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetam) ? do-3-met? l) but? l-3- (t? azol-4-? l) -p? rrol? d? n-5-carbox? l? co, Acid (+) - (2R, 3R, 5R, 1'S) -1-t-butox? Carbon? L-2- (1-acetamido-3-met? L) but? L-3- (t? Azol-2-? L) -p Hydro-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-3-methyl) but? l-3-v ? n? l? rrol? d? n-5-carboxíl? co, Acid (±) - (2R, 3S, 5R, 1'S) -2- (1-acetam? do-3-met? l) but? l -3- (2,2-d? Fluoro-v? N-1-? L) -p? Rrol? D? N-5-carboxyl? Co, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-met? L) but? L-3- (p? Razol-3-? L) -p? Rrol? D? N-5-carbox? L? Co, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-met? L) but? L-3- (? Soxazol-3? L) -p? Rrol? D n-5-carboxylic, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-Acetamido-3-met? l) but? l-3 - (? soxazol -5-? L) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3R, 5R, 1'S) -2- (1-acetamido-3-met? L) ) but? l-3- (? m? dazol-2-? l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3R, 5R, 1'S) - 2- (1 -acetamido-3-met? L) but? L-3- (? M? Dazol-4-? L) -pyrrolidone-5-caboxic acid, and Acid (±) - (2S, 3R, 5R, 1'S) -2- (1-acetamido-3-methyl) butyl-3-amidopyrrolidone-5-carboxylic acid, or a salt, an ester or an acceptable prodrug for use of the same 32 A compound selected from the group consisting of

   Acid (±) - (2R, 3S, 5R, 1'R) -2- (1-acetamido-2-et? L-2-hydrox?) But? L-3- (c? S- propen-1-? l) -p? rrol? d? n-5-carbox? l? co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox? -2-met? L) pent? L-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1- acetamido-2-et? l-2-hydrox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-hydrox?) Pent? L-3- (c? S-propen-1-) l) -pyrrolidone-5-carboxylic acid, tpfluoroacetic salt,

   Acid (±) - (2R, 3R, 5R, 1'R, 2, R) -2- (1-acetamido-2,3-d? H? Drox?) - prop? L-3- (c ? s-propen-1-? l) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetam) ? do-2-h? drox? -4-v? n? l) -but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co (-) - (2R, 3S, 5R, 1'S) -2- (1-acetamido-2-et? l) but? l-3- (c? s-propen-1-? l) -pyrrolidone-5-carboxylate, ammonium salt, acid (±) - (2R, 3S, 5R, 1'R, 2'R) -2- (1-acetamido-2) , 3-d? Methox?) - prop? L-3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carboxyl? Co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -2-v? N? L) et? L-3- (c? S-propen-1-? L ) -pyrrolidone-5-carboxylic acid, (±) - (2 R, 3S, 5R, 1'S) -2- (1 -acetamido-2-et? l) but ? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-? Soprop? LN-metí lamín- N-óx? Do)) et? L-3- (c? S-propen-1-? L) -p ? carbohydrate-5-carboxylic acid,

   Acid (±) - (2R, 3S, 5R, 1'S, 3'S) -2- (1-acetamido-2- (N-et? LN-met? Lam? NN-ox? Do)) et? L- 3- (c? S-propen-1-? L) -p? Rrol? D? N-5-carboxyl? Co,

   Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox?) But? L-3- (c? S-propen-1? ) -pyrrolidone-5-carboxylic acid, Acid (±) - (2R, 3S, 5R, 1, R, 2'S) -2- (1-Acetamido-2-methoxy?) pent ? l-3-

   (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co Acid (±) - (2R, 3R 5R, 1'R, 2'S) -2- (1 -acetam? do-2-hydrox?) but? l-3- (p? razol-3-? l) -p? rrol? d? n-5-carbox? l? co Acid (±) - ( 2R 3S 5R 1 'R, 2'S) -2- (1-acetamido-2-hydrox?) But? L-3- (cis-pro pen- 1-? L) -p? R id id 5- carboxylic acid, (±) - (2R, 3S, 5R, 1'R, 2, R) -2- (1-acetamido-1- (3,6-d? h ? d-2-Hp? rano-2-? l)) prop? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co,

   Acid (±) - (2 R, 3S, 5R, 1"R, 2" S) -2- (1 -aceta m? Do-2-methox? -2-al? Lo) et? L-3- ( c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S 5R 1'R 2'S, 3 S) -2- (1- acetamido-2-hydrox? -3-met? l) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carbox? l? co, Acid (±) - (2R 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-methox? -4-v? n? l) but? l-3- (c ? s-propen-1-? l) -p? rrol? d? n-5-ca rbox ili co, Acid (±) - (2R, 3S, 5R, 1, R, 2'S) -2- (1- acetamido-2-hydrox-3-carboxy) propyl-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-1- (3,6-d? H? Dro-2-Hp? Rano-2-? l)) met? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co,

   Acid (±) - (2R, 3S, 5R, rR, 2'S) -2- (1-acetamido-2,3-d? Methox?) Prop? L-3- (c? S-propen-1-) (l) -pyrrolidone-5-carboxylic acid, acid (±) - (2R, 3S, 5R, 1, R, 2'S) -2- (1-acetamido-2-h? drox? met? l-2-h? drox?) pent? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetamido-2-ethoxy?) Pent? L-3- (c? S-propen-1-? L) -p? r? r? d? n-5-carboxyl? co, Acid (±) - (2R, 3S, 5R, 1'R, 2'S) -2- (1-acetam? do-2-hydrox? -3-d) ? met? l) but? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5-carboxyl? co,

   Acid (±) - (2R, 3S, 5R, 1 'R, 2'S) -2- (1 -acetam? Do-2-ethoxy? -3-v? N? L) prop? L-3- (c? s-propen- 1 -? l) -p? rrol? d? n-5-carbox? l? co, Acid (+) - (2R, 3S, 5R, 1 'R, 2'S) -2- (1 - acetam? do-2-hydrox? -2- (propen-2-? l)) et? l-3- (c? s-propen-1-? l) -p? rrol? d? n-5 -carboxyl, and Acid (±) - (2R, 3S, 5R, 1 'R, 2'S) -2- (1 -acetam? do-2-h? drox?) hex? l-3- (c? s-propen-1 -? l) -p? rrol? dtn-5-carboxyl? co, or a pharmaceutically acceptable salt, ester or prodrug thereof 33 A pharmaceutical composition for inhibiting influenza neuraminidase, which comprises a pharmaceutical carrier and an effective amount of a compound of claim 1 A pharmaceutical composition for treating an influenza infection, which comprises a pharmaceutical carrier and an effective amount of a compound of claim 1 A pharmaceutical composition to prevent an influenza infection, which comprises a pharmaceutical carrier and an effective amount of a compound of the reivi 1. A pharmaceutical composition for inhibiting influenza neurammidase, which comprises a pharmaceutical carrier and an effective amount of a compound of claim 31. A pharmaceutical composition for treating an influenza infection, which comprises a pharmaceutical carrier and an effective amount of a compound of claim 31

   38. A pharmaceutical composition for preventing an influenza infection, which comprises a pharmaceutical carrier and an effective amount of a compound of claim 31. 39. A method for inhibiting neuraminidase of a disease causing microorganism, comprising administering to a human or other mammal, with the need thereof, a therapeutically effective amount of a compound of claim 1. 40. The method according to claim 39, wherein the microorganism causing the disease is a virus. 41. The method according to claim 40, wherein the virus is the influenza virus. 42. A method for treating a disease caused by a microorganism having a neuraminidase, comprising administering to a human or other mammal, with need thereof, a therapeutically effective amount of a compound of claim 1. 43. The method according to claim 42, wherein the microorganism causing the disease is a virus. 44. The method according to claim 43, wherein the virus is the influenza virus. 45.- A method for preventing a disease caused by a microorganism having a neuraminidase, which comprises administering to a human or other mammal, with the need thereof, a therapeutically effective amount of a compound of

   claim 1. 46. The method according to claim 44, wherein the microorganism causing the disease is a virus. 47. The method according to claim 46, wherein the virus is the influenza virus. 48. A method for inhibiting a neuraminidase of a microorganism causing a disease, comprising administering to a human or other mammal, with the need thereof, a therapeutically effective amount of a compound of claim 31. 49. The method according to claim 48, wherein the microorganism causing the disease is a virus. 50. The method according to claim 49, wherein the virus is the influenza virus. 51 A method for the treatment of a disease caused by a microorganism having a neuraminidase, comprising administering to a human or other mammal, with need thereof, a therapeutically effective amount of a compound of claim 31. 52. The method according to claim 51, wherein the microorganism causing the disease is a virus. 53. The method according to claim 52, wherein the virus is the influenza virus. 54. A method for preventing a disease caused by a microorganism having a neuraminidase, comprising

   administering to a human or other mammal, with need thereof, a therapeutically effective amount of a compound of claim 31. 55. The method according to claim 54, wherein the microorganism causing the disease is a virus. 56. The method according to claim 55, wherein the virus is the influenza virus.