GB1583163A

GB1583163A - Pyrrolidones and process for their manufacutre

Info

Publication number: GB1583163A
Application number: GB18427/77A
Authority: GB
Original assignee: Hoechst AG
Current assignee: Hoechst AG
Priority date: 1976-05-04
Filing date: 1977-05-03
Publication date: 1981-01-21
Also published as: FR2372806B1; JPS52133975A; BE854268A; FR2372806A1; ES458264A1; NL7704739A; IT1086223B; DE2619638A1; DK194377A

Description

(54) PYRROLIDONES AND PROCESS FOR THEIR MANUFACTURE (71) We, HOECHST AKTIENGESELLSCHAFT, a body corporate organised according to the laws of the Federal Republic of Germany, of 6230 Frankfurt (Main) 80, Postfach 80 03 20, Federal Republic of Germany, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to pyrrolidones and to a process for their production.

Prostaglandins are a group of natural substances isolated from various animal tissues. In mammals they are responsible for numerous physiological effects.

Natural prostaglandins have a carbon structure of, in general, 20 carbon atoms and are distinguished from one another, above all, by an increase or decrease in the number of hydroxyl groups or double bonds in the cyclopentane ring (with regard to the structure and effect of prostaglandins see inter alia, M. F. Cuthbert "The Prostaglandins, Pharmacological and Therapeutic Advances", William Heinemann Medical Books Ltd., London, (1973)).

The synthesis of analogues of prostanoic acids that do not occur naturally and in which the plurality of the pharmacological effects of natural prostaglandins are differentiated is increasingly gaining in importance. In German Offenlegungsschriften 2 528 664 and 2 556 326 prostaglandins in which the carbon in the 8-position of the natural prostaglandins is replaced by nitrogen, are described for the first time. Independently of this, the synthesis of a single represenative of this type is described in Tetrahedron Letters 2931 (1975).

The present invention provides a compound of the general formula I

in which R' represents a straight or branched chain, saturated or unsaturated aliphatic hydrocarbon radical having up to 10 carbon atoms or a cycloaliphatic hydrocarbon radical having 3-7 carbon atoms, which radicals can each be substituted by a) a straight or branched chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 5 carbon atoms, b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from halogen atoms, alkyl groups having 1--3 carbon atoms, phenoxy radicals, and alkoxy radicals having 14 carbon atoms which alkyl and phenoxy groups may be substituted by one or more halogen atoms, c) a furyloxy, thienyloxy or benzyloxy radical, each of which may be monosubstituted or disubstituted in the nucleus by one or two substituents selected, independently in the latter case, from halogen atoms, alkyl groups having 1-3 carbon atoms, which may be substituted by one or more halogen atoms, and alkoxy groups having 14 carbon atoms, d) a trifluoromethyl group or a pentafluoroethyl group, e) a cycloalkyl radical having 3-7 carbon atoms, f) a phenyl, thienyl, or furyl radical each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from halogen atoms, alkyl groups having 1-3 carbon atoms which may be substituted by one or more halogen atoms, and alkoxy groups having 14 carbon atoms, R2 represents a straight or branched chain, saturated or unsaturated aliphatic or cycloaliphatic radical having 2-6 carbon atoms, an araliphatic hydrocarbyl radical having 7 or 8 carbon atoms or, if R', R3, A, B and n do not simultaneously represent a hydrogen atom, an n-pentyl group, a -CH2-CH- group, a -CH=CH- group and the integer three respectively, a methyl group or a hydrogen atom R3 represents a hydrogen atom or a straight or branched chain alkyl, alkenyl, or alkynyl radical having up to 5 carbon atoms or an araliphatic hydrocarbyl radical having 7 or 8 carbon atoms, A and B each represents a -CH2-CH2- or a -CH=CH- group, wherein A and B may be the same or different but may not simultaneously be a -CH=CH- group, n represents the integer two, three or four.

The invention also provides the salts of the free acids of formula I, especially the physiologically tolerable salts thereof.

The present invention also provides a process for the production of a compound of the general formula I wherein a,) a compound of formula II

wherein R' and R3 have the meanings given for formula I and R4 represents a protective group that can be split off under acidic conditions, is deprotonated at the nitrogen atom with a base and the anion thus formed is reacted with a carboxylic acid derivative of formula III Y-CH2-CH2-CH2-(CH2)n-COOR2 III wherein R2 and n have the meanings given for formula I and Y represents an alkanesulphonyloxy radical or a benzenesulphonyloxy radical that may be substituted by one or more substituents selected from alkyl groups and halogen atoms, or Y represents a halogen atom to form a compound of formula IV

a2) the hydroxy protective group R4 is split off from the compound of formula IV by acid hydrolysis to form a compound of formula I in which A represents a -CH2-CH2- group and B a -CH=CH- group, or a2,) a compound of formula V is .reacted as described under a,) to form a compound of formula VI

wherein R1, R2 and n have the meanings given for formula I, a2,2) the exocyclic carbonyl group in the compound of formula VI is reduced or the compound of formula VI is reacted with an organometallic compound, produced from R3--X", wherein X represents a halogen atom and R3 has the meanings given for formula I with the exception of a hydrogen atom, to form a compound of formula I wherein A represents a -CH2-CH2- group and B represents a -CH=CH- group, and optionally a3) a compound of formula I in which A represents a -CH2-CH2- group and B represents a -CH=CH- group, is hydrogenated to form a compound of formula I wherein A and B each represent a -CH2-CH2- group, or a3.,) a compound of formula IV is hydrogenated to form a compound of formula VII

wherein R', R2, R3 and n have the meanings given for formula I and R4 is as defined above, and a3.2) the hydroxy protective group R4 in a compound of formula VII is split off by acid hydrolysis to give a compound of formula I wherein A and B each represents a -CH2-CH2- group, or b") in a compound of formula V

the double bond is hydrogenated to give a compound of formula VIII wherein R' has the meaning given for formula I

b1,2) the compound of formula VIII is deprotonated at the nitrogen with a base and the anion formed is reacted with an allyl halide to form a compound of formula

wherein R' has the meaning given for formula I, b13) the compound of formula IX obtained is subjected to ozonolysis whereby an aldehyde of formula X is formed

wherein R' has the meaning given for formula I, b1,4) the aldehyde of formula X obtained is reacted with an ylide of formula XI (R5)3P=CH(CH2)nCOOR2 XI wherein n and R2 have the meanings given for formula I and R2 may also represent an alkali metal cation, the symbols R5 each represents the same or different straight chain (C1-C4)-alkyl radical or phenyl radical, to form a compound of formula XII

wherein R', R2 and n have the,meanings given for formula I, b1,5) the exocyclic carbonyl group of the compound of formula XIII is reacted with an organometallic compound produced from R3-X#, wherein X# represents a halogen atom and R3 has the meaning given for formula I but may not be hydrogen, or the exocyclic carbonyl group of the compound of formula XII is reduced to form a compound of formula I wherein A represents a -CH-CH- group and B represents a -CH2-CH2- group, or b2,) the double bond in a compound of formula II is hydrogenated to form a compound of formula XIII

wherein R' and R3 have the meanings given for formula I and R4 is as defined above, b2 2) the compound of formula XIII is deprotonated at the nitrogen with a base and the anion formed is reacted with an allyl halide to form a compound of formula XIV

wherein R' and R3 have the meanings given for formula I and R4 is as defined above, b23) the compound of formula XIV is subjected to ozonolysis whereby an aldehyde of formula XV is formed

wherein R' and R3 have the meanings given for formula I and R4 is as defined above, b24) the aldehyde of formula XV is reacted with an ylide of formula XI (R5)3P=CH(CH2)nCOOR2 XI wherein n and R2 have the meanings given for formula I and R2 may also represent an alkali metal cation and the symbols R5 is as defined above, to form a compound of formula XVI

wherein R', R2, R3 and n have the meanings given for formula I and R4 is as defined above, b2 5) the protective group R4 is split off from the compound of formula XVI by acid hydrolysis to form a compound of formula I wherein A represents a -CH=CH- group and B represents a -CH2-CH2- group, and optionally b3) a compound of formula I, wherein A represents a -CH=CH- group and B represents a -CH2-CH2- group, is hydrogenated to form a compound of formula I wherein A and B each represent a -CH2-CH2- group, or b4,) the exocyclic carbonyl group in the compound of formula VIII is reduced, or the compound of formula VIII is reacted with an organometallic compound produced from R3-X, wherein X represents a halogen atom and R3 has the meaning mentioned for formula I but cannot represent hydrogen, to form a compound of formula XVII

wherein R' and R3 have the meanings given for formula I and b4,2) the compound of formula XVII is deprotonated at the nitrogen with a base and the anion formed is reacted with a carboxylic acid derivative of formula XVIII

wherein R2, A and n have the meanings given for formula I and Y is as defined above, whereby a compound of formula I is formed, wherein A represents a H2-CH2- or a --CH=CH-- group and B represents a H2-CH2- group, or c1) a compound of formula VIII is deprotonated at the nitrogen atom with a base and the anion formed is reacted with a carboxylic acid derivative of formula III whereby a compound of formula XIX is formed

wherein R', R2 and n have the meanings given for formula I and c2) the exocyclic carbonyl group of the compound of formula XIX is reduced, or the compound of formula XIX is reacted with an organometallic compound produced from R3--X", wherein X represents a halogen atom and R3 has the meaning mentioned for formula I but cannot represent hydrogen, to form a compound of formula I wherein A and B each represent a -CH2-CH2- group, or d) a compound of formula XX

is hydrogenated to form a compound of formula I wherein A and B each represent a -CH2-CH2- group, or e) any one or more of the steps defined above is carried out analogously using a reactant analogous to a compound as defined above but in which a free hydroxyl group is present instead of a group OR4, or a group OR4 is present instead of a free hydroxyl group, as appropriate, R4 being as defined above, and f) if desired, a free acid of formula I resulting from any of the above reactions is converted into a salt thereof, especially a physiologically tolerable salt.

Of the meanings given for the symbols R1, R2 and R3, n, A and B, the following are preferred: For R1: a straight or branched chain, saturated or unsaturated, aliphatic radical having up to 7 carbon atoms or a cycloaliphatic radical having 57 carbon atoms, which radicals can each be substituted by a) a straight or branched chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 4 carbon atoms b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1---3 carbon atoms, methoxy and ethoxy groups, trifluoromethyl groups, halogen atoms, and phenoxy radicals which may be substituted by one or more halogen atoms, c) a thienyloxy or benzyloxy radical, each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1--3 carbon atoms, trifluoromethyl groups, halogen atoms, methoxy and ethoxy groups d) a trifluoromethyl group, e) a cycloalkyl radical having 5-7 carbon atoms, f) a phenyl radical or thienyl radical each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1--3 carbon atoms, trifluoromethyl groups, halogen atoms, and methoxy and ethoxy groups.

For R2: a straight or branched chain alkyl radical having 1--6 carbon atoms, a straight or branched chain alkenyl radical having 2--4 carbon atoms, a cycloalkyl radical having 5 or 6 carbon atoms or an aralkyl radical having 7 or 8 carbon atoms.

For R3: a hydrogen atom, a straight or branched chain alkyl radical having 1 to 5 carbon atoms, an alkenyl radical or alkynyl radical having 2 to 5 carbon atoms.

The following meanings, in particular, are preferred: For R1: a straight or branched chain alkyl radical having 1--7 carbon atoms, a straight or branched chain alkenyl radical having 3-5 carbon atoms or a cycloalkyl radical having 5-7 carbon atoms, which radicals may be substituted by: a) a straight or branched chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 3 carbon atoms, b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, and phenoxy radicals optionally substituted by chlorine and/or fluorine atoms, c) a thienyloxy or benzyloxy radical each of which may be monosubstituted or disubstituted in the nucleus by one or two substituents selected independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, d) a trifluoromethyl group, e) a cycloalkyl radical having 5-7 carbon atoms, f) a phenyl radical or thienyl radical each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, For R2: a straight chain alkyl radical having 1 to 6 carbon atoms, a branched chain alkyl radical having 3-5 carbon atoms, a straight chain alkenyl radical having 24 carbon atoms, a cyclopentyl or cyclohexyl radical or a benzyl radical.

For R3: a hydrogen atom, a methyl, ethyl or propyl radical or an alkenyl or alkynyl radical having 2 or 3 carbon atoms, and n preferably represents the integer 3. Compounds in which B represents the -CH2-CH2 group are especially preferred.

Of the substituents for R1 the following, for example, are particularly preferred: 2,2 - dimethylhexyl, 3,3 - dimethylhexyl, 4,4 - dimethylhexyl, 3 - ethylpentyl, 1,1 - dimethyl - 4 - pentenyl, 5 - methyl - 4 - hexenyl, 1 - methyl - 5 cyclohexylpentyl, 4 - cycloheptylbutyl, 5,5,5 - trifluoropentyl, 6,6,6 trifluorooctyl, 1,1 - dimethyl - 7,7,7 - trifluoroheptyl, 1 - methyl - 6,6,6 trifluorohexyl, 1,1 - difluoro - 4,4 - dimethylpentyl, 4,4 - difluorocyclohexyl, 4 trifluoromethylcyclohexyl, 3 - trifluoromethylcyclohexyl, 2 trifluoromethylcycloheptyl, 3 - trifluoromethylcyclopentyl, 3,3 - dimethyl - 2 oxapentyl, 3 - methyl - 2 - oxahexyl, 4,4 - dimethyl - 2 - oxapentyl, 1,1,4 trimethyl - 2 - oxa - pentyl, 3,4 - dimethyl - 2 - oxapentyl, 5 - methyl - 2 - oxa4 - hexenyl, 2,2 - dimethyl - 3 - oxaheptyl, 1,1 - dimethyl - 3 - oxahexyl, 1,1 dimethyl - 3 - oxaoctyl, 1,1,5,5 - tetramethyl - 3 - oxahexyl, 1 - methyl - 3 oxahexyl, I - methyl - 3 - oxaoctyl, 1,1,6 - trimethyl - 3 - oxa - 5 - heptenyl, 1,1,6 - trimethyl - 3 - oxaheptyl, 7 - methyl - 4 - oxaoctyl, 1,1 - dimethyl - 4 oxa - 6- heptenyl, 4 - methoxycyclohexyl, 3 - butoxycyclohexyl, 2ethoxycyclohexyl, 3 - ethoxycyclopentyl, 4 - methoxycycloheptyl, 2 - thiapentyl, 2 - thiahexyl, 2 - thiaheptyl, 4,4 - dimethyl - 2 - thiapentyl, 5 - methyl - 2 - thia 4 - hexenyl, 3 - thiapentyl, 3 - thiahexyl, 5,5 - dimethyl - 3 - thiahexyl, 1,1 dimethyl - 3 - thiapentyl, 1,1 - dimethyl - 4 - thiapentyl, 4 chlorophenoxymethyl, 2 - chlorophenoxymethyl, 2,3 - dichlorophenoxymethyl, 2,4 - dichlorophenoxymethyl, 2,5 - dichlorophenoxymethyl, 2,6 dichlorophenoxymethyl, 3,4 - dichlorophenoxymethyl, 3,5 dichlorophenoxymethyl, 2 - chloro - 6 - methylphenoxymethyl, 2 - chloro - 4 methylphenoxymethyl, 3 - chloro - 2 - methylphenoxymethyl, 4 - chloro - 2 methylphenoxymethyl, 5 - chloro - 2 - methylphenoxymethyl, 4trifluoromethylphenoxymethyl, 2 - trifluoromethylphenoxymethyl, 2 - methyl - 5 - trifluoromethylphenoxymethyl, 3 - methyl - 5 trifluoromethylphenoxymethyl, 3 - fluorophenoxymethyl, 2 fluorophenoxymethyl, 2 - fluoro - 4- trifluoromethylphenoxymethyl, 3,4 difluorophenoxymethyl, 4 - fluoro - 2- methylphenoxymethyl, 4 phenoxy phenoxymethyl, 3 - p - chlorophenoxyphenoxymethyl, 4 methoxyphenoxymethyl, 3 - methoxyphenoxymethyl, 4- chloro - 3 methoxyphenoxymethyl, 3 - chloro - 4 - methoxyphenoxymethyl, 4 - methoxy 3 - methylphenoxymethyl, 4 - methoxy - 2 - methylphenoxymethyl, 3 methoxy - 5 - methylphenoxymethyl, 2 - (3 - chlorophenoxy)ethyl, 2- (4- chlorophenoxy)ethyl, 2- (3 - trifluoromethylphenoxy)ethyl, 2 - (4 methoxyphenoxy)ethyl, 2 - (3 - methylphenoxy)ethyl, 2 - (4 fluorophenoxy)ethyl, 2 - (3 - chloro - 5 - methylphenoxy)ethyl, I - methyl - 2 (3 - trifluoromethylphenoxy)ethyl, I - methyl - 2 - (3 - chlorophenoxy)ethyl, 1 - methyl - 2- (4- fluorophenoxy)ethyl, I - methyl - 2-(4-chloro- 3methylphenoxy)ethyl, I - methyl - 2 - (3 - chloro - 4 - methoxyphenoxy)ethyl, 2 - (3 - trifluoromethyl - phenoxy) - 1,1 - dimethylethyl, 2 - (3 chlorophenoxy) - 1,1 - dimethylethyl, 2 - (4 - fluorophenoxy) - 1,1 dimethylethyl, 2 - (3,4 - dichlorophenoxy) - 1,1 - dimethylethyl, 2 - (3 - chloro 4 - methylphenoxy) - 1,1 - dimethylethyl, 2 - (3 - chloro - 4 - phenoxyphenoxy) 1,1 - dimethylethyl, 1,1 - dimethyl - 4 - phenoxybutyl, 1,1 - dimethyl - 4 - (3 trifluoromethylphenoxy)butyl, benzyloxymethyl, 3 - chlorobenzyloxymethyl, 3 trifluoromethylbenzyloxymethyl 4 - methoxybenzyloxymethyl, 3 phenoxybenzyloxymethyl, 2 - methylbenzyloxymethyl, 4 - chloro - 3 methoxybenzyloxymethyl, 3 - methoxy - 5 - methylbenzyloxymethyl, 2 - (3 - chlorobenzyloxy) - 1,1 - dimethylethyl, I - methyl - 2 - (4 trifluoromethylbenzyloxy)ethyl, 3 - (4 - fluorobenzyloxy)propyl, 4- (3 chlorophenoxy)- cyclohexyl, 4 - (3 - trifluoromethylphenoxy)cyclohexyl, 2phenoxycyclohexyl, 4- (2 - chlorobenzyloxy)- cyclohexyl, benzyl, 3 trifluoromethylbenzyl, 4 - methylbenzyl, 2 - (3 - chlorophenyl)ethyl, 2- (4- fluorophenyl)ethyl, a,a - dimethylphenethyl, 1,1 - dimethyl - 3 - phenylpropyl, 2 - methyl - 3 - thienyloxymethyl, 2 - chloro - 3 - thienyloxymethyl, 2 - chloro 4 - thienyloxymethyl, 3 - chloro - 4 - thienyloxymethyl, 2,5 - dimethyl - 3 thienyloxymethyl, 2- chloro - 3 - methyl - 4 - thienyloxymethyl, 2 thienyloxymethyl, 4- methyl - 2- thienyloxymethyl, 5 - chloro - 2 thienyloxymethyl, 5 - chloro - 3 - methyl - 2 - thienyloxymethyl, 3,5 - dimethyl 2 - thienyloxymethyl, 2 - (3 - thienyl) - 1,1 - dimethylethyl, 3 - (3 - thienyl) - 1 methylpropyl, 3 - (2 - methoxy - 4 - thienyl) - propyl, 3 - thenyl, 2 - chloro - 4 thenyl, 2 - methyl - 5 - thenyl, 4 - (3 - thienyl)butyl, 1,1 - dimethyl - 3 - (3 thienyl)propyl, 2 - (4 - methoxy - 2 - thienyl)ethyl.

The compounds of formulate II (R3=H) and V used as starting materials for the processes mentioned under a) may be synthesized according to the conditions mentioned in German Offenlegungsschrift 2 528 664. The compounds of formula II (R3+H) can be produced according to the information given in German Offenlegungsschrift 2 556 326.

The compounds of formulae II and V may be alkylated with a carboxylic acid derivative of formula II according to conventional methods, for example, the nitrogen is deprotonated with a suitable base, for example, sodium hydroxide or potassium hydroxide, sodium amide or potassium amide, sodium hydride, potassium tert.-butoxide lithium diisopropylamide or lithium cyclohexylisopropylamide, and then the alkylating agent of formula III is added as such or dissolved in a suitable appropriate solvent.

The radical Y in the compound of formula III is, for example, methanesulphonyloxy, p - bromobenzenesulphonyloxy, or p toluenesulphonyloxy but chlorine, bromine and iodine atoms are preferred, bromine and iodine being of the most importance.

The reaction of the base with the compound of formulae II and V is effected with the exclusion of air and moisture because of the sensitivity to air and moisture of the bases and the resulting carbanions. Suitable solvents are, in particular, aprotic polar liquids which still have sufficient dissolving power even at low temperatures and which are inert under the reaction conditions. Optionally, a mixture of two or more solvents may be used to lower the solidification point.

Preferred solvents are, for example, ethers, for example, dimethyl ether, diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, and glycol dimethyl ether, also dimethylformamide, dimethyl sulphoxide, and toluene. The reaction temperatures are generally from -300C to +1000C, preferably from -10"C to +800C.

Working-up can, for example, be carried out by adding a predetermined amount of water to the reaction mixture, separating the organic phase, extracting the aqueous phase several times with an organic solvent and drying and concentrating the combined organic phases. In a very small number of cases the residue must be purified by high vacuum distillation but in most cases it can be purified by column chromatography. The products are often already so pure when formed that purification is not necessary.

A compound of formula I in which A is -CH2-CH2-, B is -CH=CH- and R3 is hydrogen can be obtained by treating the compound of formula VI with a reducing agent. Reduction can be effected with any reducing agent that renders possible the selective reduction of an exocyclic carbonyl group to form a hydroxyl group. Preferred reducing agents are complex metal hydrides, in particular borohydrides, for example, sodium borohydride, zinc borohydride or lithium perhydro-9b-boraphenalkyl hydride (J. Amer. Chem. Soc. 92, 709 (1970)), and also complex aluminium hydrides, for example, sodium - bis - (2 - methoxyethoxy) aluminium hydride. Reduction is normally carried out at a temperature of from -10" to +500C in a solvent which is inert with regard to the hydrides, for example, an ether, for example, diethyl ether, 1,2 - dimethoxyethane, dioxane, tetrahydrofuran or diethylene glycol dimethyl ether or a hydrocarbon, for example, benzene, or in an alcohol/water mixture, for example, methanol/water. The isomeric a- and hydroxy compounds formed during this reduction can be separated into the two isomers by means of conventional chromatographic methods.

The organometallic compounds used for converting a compound of formula VI into a compound of formula I in which A is -CH2-CH2-, B is -CH=CH- and R3 does not represent a hydrogen atom, are derived from metals of the 1st and 2nd main groups. Particularly suitable compounds are organic lithium and organo - magnesium compounds (Grignard compounds) that are produced in any of the usual ways, e.g., from a compound R3--X", wherein R3 has the meaning given for formula I and X represents a halogen atom, for example, a chlorine, bromine or iodine atom, and the corresponding metal, for example Li or Mg.

Suitable solvents for the reaction of the pyrrolidones of formula VI are those that are inert under the reaction conditions, for example, hydrocarbons or, preferably, ethers, for example, diethyl ether, tetrahydrofuran and 1,2dimethoxyethane. The reaction is generally effected at a temperature of from -600C to +300C, preferably from -300 C to 00 C. The substrate may be added to the organometallic compound or the organometallic compound to the substrate, but the organometallic compound is preferably added to the substrate in order to prevent side reactions that might possibly occur. For working-up, water, a dilute mineral acid or a solution of an ammonium salt, for example, ammonium chloride in water, is added and the reaction product is isolated in the normal manner.

To split off the hydroxy protectinggroup from a compound of formula IV to give a compound of formula I (A: -CH2-CH2-, B: -CH=CH-), the usual reagents and reaction conditions may be used.

In the compound of formula IV, the hydroxy group is preferably protected by formation of an acetal group. The easiest method of splitting off this protective group, which results in a compound I, is by acidic hydrolysis with dilute aqueous/alcoholic acid, preferably in dilute aqueous/alcoholic oxalic acid at 100-- 50"C or by heating with 50--700/, acetic acid to 50--600C.

The hydrogenation of a compound of formula I in which A is -CH2-CH2- and B is -CH=CH- to form the corresponding compound of formula I in which both A and B are -CH2-CH2- may be carried out successfully under the conditions usual for hydrogenating a carbon-carbon double bond. Suitable catalysts are metal catalysts, for example, nickel, noble metal catalysts, for example, palladium as such or on a carrier, for example barium carbonate or an active carbon. An alcohol, for example, methanol, is generally used as a solvent.

The temperature range and pressure range can vary to a great extent, the temperature range of from room temperature to 600C and the pressure range of up to 10 atm being particularly important.

As described above, a compound of formula IV can alternatively be hydrogenated to form a compound of formula VII. Splitting off the hydroxy protecting group from a compound of formula VII according to the instructions given for the conversion of IV to I (A: -CH2-CH2-, B: -CH=CH-) yields the corresponding compound of formula I (A,B: -CH2-CH2-).

The compounds of formula VI and I wherein R3 represents hydrogen, can also be synthesized in a manner analogous to the instructions given in Tetrahedron Letters 2931 (1975).

The hydrogenation operations, i.e. the conversion of IV to VII, V into VIII, I (A: -CH=CH-, B: -CH2-CH2-, or A: -CH2-CH2-, B: -CH=CH-) into I (A,B: ID=1 reaction mixture with a suitable solvent, for example, diethyl ether, methylene chloride or benzene, the organic phase is dried and concentrated.

The reaction steps just described for converting IX into XII can also be applied, in a similar manner, to the conversion of XIV to XVI.

In addition to the processes described in detail here the invention also includes those processes that are derived in analogous manner from the reaction stages indicated here. Included in these processes are, in particular, those process steps that are effected on compounds that differ from one another only in an increased content or decreased content of one or various protective groups (e.g. conversion of XIII (R4=H) into XVI (R4=H).

The reduction of the exocyclic carbonyl group, which is introduced by the Horner reaction, or the reaction of this carbonyl group with an organo-metallic reagent yields a mixture of a- and p-isomers with regard to the resulting secondary or tertiary hydroxyl group. The separation into the two epimers can be effected either on these reaction products or, after any of the subsequent reaction stages.

This means that all subsequent reactions, e.g. hydrogenation, conversion into the free acid or esterification or conversion into metal salts or amine salts can be effected either on the pure a- and p-isomers or on a mixture of a- and p-isomers.

If the various intermediates are not obtained in pure form, purification, e.g. by column, thin layer or high-pressure liquid chromatography is recommended.

The compounds of formula I have two asymmetric centres, viz. the carbon atom that carries the secondary or tertiary hydroxyl group, and the carbon atom adjacent to the nitrogen in the five-membered ring, which carbon atom corresponds to the 5-position in the pyrrolidone ring.

Since none of the reactions indicated yields sterically uniform products, the invention relates to all compounds of formula I irrespective of the steric arrangement at the various carbon atoms. As well as the two optically isomeric carbon atoms already mentioned above, this also applies to the geometrically isomeric compounds regarding the double bond. However, it can generally be assumed that, in the case of the Horner reaction, as a result of the reaction carried out, a trans linkage will mainly be obtained and the cis-product, occurring only to a slight extent, may be removed by chromatographic purification operations.

Similarly, in the Wittig reaction for introducing the carboxyl side chain, the corresponding cis-olefin is chiefly formed. In this case, the trans-olefin occurring as a by-product may be separated by appropriate purification operations.

The geometry of the double bond predetermined in the carboxylic acid derivatives XVIII (A: -CH=CH-) is transferred by the alkylating operation to the subsequent end products. This means that, when using a trans-derivative XVIII (A: -CH=CH-), the product carries a trans-double bond in the carboxyl side chain.

Analogously the same applies to the use of the cis-derivative XVIII (A: -CH=CH-).

On the basis of the possibilities for introducing the two double bonds, it may be assumed that the geometry of the double bond is uniform. The mixture of two diasteromers present as a result of the two optically isomeric carbon atoms can be separated, in the case of crystallizable derivatives, by fractional crystallisation or by means of chromatographic methods, for example, column gas, thin layer, or medium or high pressure liquid chromatography, into the two racemic diasteromers. The racemates may be split up into the optically active compounds according to conventional processes, for example, treatment of the compound of formula I (R2=H) with an optically active base, for example, e.g. brucine.

Apart from the compounds mentioned in the examples, the following compounds, in particular, can also be produced.

TABLE I 1 - (5 - Methoxycarbonylpentyl) - 5 - (3 - hydroxy - octyl) - 2 - pyrrolidone 1 - (5 - Methoxycarbonylpentyl) - 5 - (3 - hydroxy - 4,4 - dimethyf - 5 ethoxypentyl) - 2 - pyrrolidone 1 - (5 - Methoxycarbonylpentyl)- 5 - (3 - hydroxy - 7,7,8,8,8 pentafluorooctyl) - 2 - pyrrolidone I - (5 - Methoxycarbonylpentyl) - 5 - [3 - hydroxy - 4- (3 - thienyloxy)butyl] - 2 - pyrrolidone I - (5 - Methoxycarbonylpentyl) - 5 - [3 - hydroxy - 5 - phenyl - pentyl] - 2 - pyrrolidone 1 - (5 - Methoxycarbonylpentyl) - 5 - (3 - hydroxy - 4,4 - dimethyloctyl) 2 - pyrrolidone 1 - @ (5 - Methoxycarbonylpentyl) - 5 - [3 - hydroxy - 4 - (3 - trifluoromethylphenoxy) - butyll - 2 - pyrrolidone 1 - - (7 - n - Propoxycarbonylheptyl) - 5 - (3 - hydroxy - 3 - allyloctyl) - 2 pyrrolidone 1 - (7- iso - Amyloxycarbonylheptyl) - 5 - (3 - hydroxy - 3 isopropyloctyl) - 2 - pyrrolidone -, (7 - Carboxyheptyl) - 5 - [3 - hydroxy - 4 - (4 - methoxyphenoxy) butyl] - 2 - pyrrolidone 1 - - (5 - n - Butoxycarbonylpentyl) - 5 - [3 - hydroxy - 4 - (3 - chloro - 4 methylphenoxy) - butyl] - 2 - pyrrolidone 1 - (6 - Carboxyhexyl) - 5 - [3 - hydroxy - 4 - (5 - methyl - 3 thienyloxy)butyl] - 2 - pyrrolidone I -(6 - Phenylethoxycarbonylhexyl) - 5 - [3 - hydroxy - 4 -(4,5 - dimethyl 3 - thienyloxy) - butyl] - 2 - pyrrolidone 1 - - [6 - n - Butoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - octyl] 2 - pyrrolidone [ - [6 - n - Hexyloxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 3 benzyloctyll - 2 - pyrrolidone 1 - [5 - Ethoxycarbonyl - (Z) - 2 - pentenyl] - 5 - [3 - hydroxyoctyl] - 2 pyrrolidone 1 - - [7 - Phenethoxycarbonyl - (Z) - 2 - heptenyl] - 5 - [3 - hydroxyoctyl] 2 - pyrrolidone 1 - [6 - Methoxycarbonyl - (Z)- 2 - hexenyl] - 5 - [3 - hydroxy - 3 ethynyl - octyl] - 2 - pyrrolidone 1 - - [7 - Methoxycarbonyl - (Z) - 2 - heptenyl] - 5 - [3 - hyroxyundecyl] 2 - pyrrolidone 1 - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - (E,E) 4,6 - octadienyl] - 2 - pyrrolidone 1 - - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 5 cyclopentyl - pentyl] - 2 - pyrrolidone 1 - [6 - Carboxy -(Z) - 2 hexenyl] - 5 - [3 - hydroxy - 5 - phenyl - butyl] 2 - pyrrolidone - 2 1 - [6 - Carboxy - (Z)- 2 - hexenyl] - 5 - [3 - hydroxy - 7,7,8,8,8 pentafluorooctyl] - 2 - pyrrolidone 1 - - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 5 ethoxypentyl] - 2 - pyrrolidone 1 - - [6 - n - Hexyloxycarbonyl - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 6 methylthiohexyll - 2 - pyrrolidone - - [6 - Carboxy - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 5 - isobutyloxy - 4,4 - dimethylpentyl] - 2 - pyrrolidone - - [5 - Carboxy - (Z) - 2 - pentenyl] - 5 - [3 - hydroxy - 5 - allylthio - 4,4 - dimethylpentyl] - 2 - pyrrolidone 1 - [5 - Carboxy - (Z)- 2 - pentenyll - 5 - [3 - hydroxy - 4 - (4 methylphenoxy) - butyl] - 2 - pyrrolidone 1 - - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (3 chlorophenoxy) - butyll - 2 - pyrrolidone 1 - [5 - Methoxycarbonyl - (Z) - 2 - pentyl] - 5 - [3 - hydroxy - 4 - (4 methoxyphenoxy) - butyl] - 2 - pyrrolidone 1 - - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (4 phenoxyphenoxy) - butyl] - 2 - pyrrolidone - - [6 - Ethoxycarbonyl - (7) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (4 - chlorophenoxyphenoxy) - 4 - methylbutyl] - 2 - pyrrolidone 1 - [5 - Ethoxycarbonyl - (Z) - 2 - pentenyl] - 5 - [3 - hydroxy - 4 - (3 chlorophenoxy) - butyl] - 2 - pyrolidone 1 - [5 - Isopropoxycarbonyl - (Z) - 2 - pentenyl] - 5 - [3 - hydroxy - 4 - (2 chloro - 4 - methylphenoxy) - butyl] - 2 - pyrrolidone 1 - [7 - Methoxycarbonyl - (Z) - 2 - heptenyl] - 5 - [3 - hydroxy - 4 - benzyloxybutyl] - 2 - pyrrolidone 1 - - [7 - Ethoxycarbonyl - (7) - 2 - heptenyl] - 5 - [3 - hydroxy - 4 - (5 methyl - 3 - thienyloxy) - butyl] - 2 - pyrrolidone - - [7 - Ethoxycarbonyl - (7) - 2 - heptenyl] - 5 - [3 - hydroxy - 4 - (4,5 - dimethyl - 3 - thienyloxy) - butyl] - 2 - pyrrolidone - - [5 - Ethoxycarbonyl - (E) - 2. - pentenyl] - 5 - [3 - hydroxy - 4 - (4 - fluorobenzyloxy) - butyl] - 2 - pyrrolidone 1 - [6 - Carboxy - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (3 trifluoromethylbenzyloxy) - butyl] - 2 - pyrrolidone 1 - [6 - n - Hexyloxycarbonyl - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 (4 - methoxybenzyloxy) - butyl] - 2 - pyrrolidone 1 -[6 -Carboxy -(E) -2 -hexenyl] -5 -[3 -hydroxy -4 -(2 -chloro -4 methylbenzyloxy) - butyl] - 2 - pyrrolidone 1 - [6 - Carboxy - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 8,8,8 trifluoromethyloctyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonyl - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 3 - ethyl 5 - cyclopentylpentyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 cycloheptylbutyl] - 2 - pyrrolidone 1 - [6 - Ethoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (4 chlorophenyl) - butyl] - 2 - pyrrolidone 1 - [6 - n - Butoxycarbonyl - (Z) - 2 - hexenyl] - 5 - [3 - hydroxy - 5 - (3,4 dichlorophenyl) - pentyl] - 2 - pyrrolidone 1 - [6 - Carboxy - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 5 - (4 - tolyl) pentyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonyl - (E) - 2 - hexenyl] - 5 - [3 - hydroxy - 4 - (5 methyl - 3 - thienyl) - butyl] - 2 - pyrrolidone 1 - [6 - Carboxy - (E) - hexenyl] - 5 - [3 - hydroxy - 4,4 - dimethyl - 5 - (4 methoxyphenyl) - pentyl] - 2 - pyrrolidone 1 - [6 - n - Butoxycarbonylhexyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] - 2 pyrrolidone 1 - [6 - n - Hexyloxycarbonylhexyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] 2 - pyrrolidone 1 - [5 - Ethoxycarbonylpentyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] - 2 pyrrolidone 1 - [7 - Ethoxycarbonylheptyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] - 2 pyrrolidone 1 - [6 - Phenethoxycarbonylhexyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] 2 - pyrrolidone 1 - [6 - Isoamyloxycarbonylhexyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] - 2 pyrrolidone 1 - [6 - Isopropyloxycarbonylhexyl] - 5 - [3 - hydroxy - (E) - 1 - octenyl] 2 - pyrrolidone 1 - [6 - Methoxycarbonylhexyl] - 5 - [3 - hydroxy - 3 - isopropyl - (E) - 1 octenyl] - 2 - pyrrolidone 1 - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 3 - ethynyl - (E) - 1 - octenyl] 2 - pyrrolidone 1 - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 3 - benzyl - (E) - 1 - octenyl] 2 - pyrrolidone 1 - [6 - Methoxycarbonylhexyl] - 5 - [3 - hydroxy - 5 - ethoxy - (E) - 1 pentenyl] - 2 - pyrrolidone 1 - [6 - n - Hexyloxycarbonylhexyl] - 5 - [3 - hydroxy - 6 - methylthio (E) - 1 - hexenyl] - 2 - pyrrolidone I - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 5 - isobutoxy - 4,4 - dimethyl (E) - 1 - pentenyl] - 2 - pyrrolidone 1 - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 5 - allylthio - 4,4 - dimethyl (E) - 1 - pentenyl] - 2 - pyrrolidone - - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 4 - (4 - methylphenoxy) - (E) 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (4 chlorophenoxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [5 - Methoxycarbonylpentyl] - 5 - [3 - hydroxy - 4 - (4 methoxyphenoxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (4 phenoxyphenoxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Ethoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (4 chlorophenoxyphenoxy) - 4 - methyl - (E) - 1 - butenyl] - 2 pyrrolidone 1 - [6 - Ethoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (3 - chlorophenoxy) (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Isopropoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (2 - chloro - 4 methylphenoxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Methoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - benzyloxy - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Ethoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (5 - methyl - 3 thienyloxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Ethoxycarbonylhexyl] - 5 - [3 - hydroxy - 4 - (4,5 - dimethyl - 3 thienyloxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [5 - Ethoxycarbonylpentyl] - 5 - [3 - hydroxy - 4 - (4- fluorobenzyloxy (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 3 - methyl - 4 - (3 trifluoromethylbenzyloxy) - (E) - 1 - butenyl] - 2 - pyrrolidone I - [6 - n - Hexyloxyhexyl] - 5 - [3 - hydroxy -4 - (4 - methoxybenzyloxy) (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [6 - Carboxyhexyl] - 5 - [3 - hydroxy - 4 - (2 - chloro - 4 methylbenzyloxy) - (E) - 1 - butenyl] - 2 - pyrrolidone 1 - [7 - Carboxyheptyl] - 5 - [3 - hydroxy - 8,8,8 - trifluoro - (E) - 1 heptenyll - 2 - pyrrolidone 1 - [7 - Methoxycarbonylheptyl] - 5 - [3 - hydroxy - 5 - cyclopentyl - (E) 1 - pentenyl] - 2 - pyrrolidone 1 - [7 - Methoxycarbonylheptyl] - 5 - [3 - hydroxy - 4 - cycloheptyl - (E) 1 - butenyl] - 2 - pyrrolidone 1 - [7 - Ethoxycarbonylheptyl] - 5 - [3 - hydroxy - 4 - (4- chlorophenyl) (E) - 1 - butenyl] - 2 - pyrrolidone I - [5 - n - Butoxycarbonylpentyl] - 5 - [3 - hydroxy - 5 - (3,4 - dichlorophenyl) - (E) - 1 - pentenyl] - 2 - pyrrolidone 1 - [5 - Carboxypentyl] - 5 - [3 - hydroxy - 5 - (4 - tolyl) - (E) - 1 - pentenyll - 2 - pyrrolidone I - 15 - Methoxycarbonylpentyl] - 5 - [3 - hydroxy - 4 - (5 - methyl - 3 thienyl) - (E) - I - butenyl] - 2 - pyrrolidone 1 - [5 - Carboxypentyl] - 5 - [3 - hydroxy - 4,4 - dimethyl - 5 - (4 methoxyphenyl) - (E) - 1 - pentenyl] - 2 - pyrrolidone The compounds of the invention have spasmogenic, bronchodilatory, vasoactive (i.e. vasoconstricting and vasodilating), and abortive properties and also properties regarding inhibition of the secretin of gastric juices. They may therefore be used as medicaments.

The invention accordingly provides a pharmaceutical preparation which comprises a compound of the general formula I or a physiologically tolerable salt thereof as active substance, in admixture or conjunction with a pharmaceutically suitable carrier.

Inorganic, physiologically tolerable salts are, for example, alkali metal salts, salts of the alkaline-earth metals and ammonium salts, and salts with organic bases are, for example, those derived from primary, secondary or tertiary amines, for example, salts with methyl, triethyl, benzyl, phenethyl, and allyl amines, and with piperidine, pyrrolidine, morpholine, ethanolamine, triethanolamine, and tris (hydroxymethyl) methylamine. Esters of formula I are preferably the esters with lower aliphatic alcohols, for example, methyl, ethyl, propyl, butyl and hexyl esters, as well as the benzyl ester.

The active substance may be in the form of an aqueous solution or suspension, or may be dissolved or suspended in a pharmaceutically suitable organic solvent, for example, a monovalent or polyvalent alcohol, for example, ethanol, ethylene glycol or glycerin, an oil, for example, sunflower oil or cod liver oil, an ether, for example, diethylene glycol dimethyl ether, a polyether, for example, polyethylene glycol, or in the presence of a pharmaceutically suitable polymer carrier, for example, polyvinylpyrrolidine.

Preparations of the invention may be in a form suitable for infusion or injection, for oral administration, for example, tablets, or for local administration, for example, creams, emulsions, suppositories and, especially, aerosols.

The pharmaceutical preparations may also comprise one or more other active substances, for instance, compounds and hormones affecting fertility, for example, LH-RH (Luteinising hormone releasing hormone), FSH, oestradiol and LH, diuretic agents, for example, furosemide, anti-diabetic agents, for example, glycodiazine, tolbutamide, glibenclamid, phenformin, buformin, metformin, circulatory agents in the widest sense, e.g. coronary dilators for example, chromonar or prenylamine, hypotensors, for example, reserpine, a-methyldopa, clonidine anti-arrhythmic agents, lipid reducers and geriatric agents and other metabolically active preparations, psychopharmacological agents, for example, chlordiazepoxide, diazepam and meprobamate, as well as vitamins, prostaglandins, compounds similar to prostaglandins and also prostaglandin antagonists.

The compounds of formulae IV, VI, VII, VIII, IX, X, XII, XIII, XIV, XV, XVI, XVII and XIX are valuable new intermediate products for the preparation of compounds of formula I, and the compounds of formulae IV, VI, VII, XII, XVI and XIX are themselves part of the invention.

The following examples illustrate the invention. The preparations of solvents used in chromatography are by volume.

Example I 1. l-(6-methoxycarbonylhexanyl)-5-(3-hydroxyoctyl)-2-pyrrolidone 1 mmol of 1 - (6 - methoxycarbonyl - (Z) - 2 - hexenyl) - 5 - (3 - hydroxy (E)- 1 - octenyl) - 2 - pyrrolidone is dissolved in 10 ml of ethanol and hydrogenated with 5% palladium on carbon at normal pressure and room temperature. The catalyst is filtered off after the absorption of hydrogen is complete, the solvent is concentrated and the remaining oil is chromatographed. Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR =3.7 ppm (s) COOCH3 3 protons IR 1680 cm-l vC=0 1735 cm-l vC=0 The following compounds are synthesized from the basic di-unsaturated compounds as indicated in the above instructions. Unless otherwise indicated, the chromatographic purification of the compounds was effected on silica gel with the eluting agent: Toluene/ethyl acetate/methanol 5:4:0.3 2. 1-(6-methoxycarbonylhexyl)-5-(3-hydroxydecanyl)-2-pyrrolidone NMR a=3.65 ppm (s) COOCH3 3 protons IR 1680 cm-' vC=0 1735 cm-' vc=0 3. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 4,4,dimethyl - 5 ethoxypentyl) - 2 - pyrrolidone NMR 6=0.9 ppm (s) C(CH3)2 6 protons b=3.7 ppm (s) COOCH3 3 protons IR 1685 cm-' vC=0 1735 cm-' vC=0 4. 1 - (6 - methoxycarbonylhexyl) - 5 - [3 - hydroxy - 4 - (4 - chlorophenoxy) phenoxy - 4,4 - dimethylbutyl] - 2 - pyrrolidone NMR a=1.05 ppm (s) C(CH3)2 6 protons =3.7 ppm (s) COOCH3 6 protons #=6.9-7.9 ppm (m) aromatic protons # protons IR 1680 cm-1 #C=0 1730 cm.-1 #C=0 5. 1 - (6 - methoxycarbonylhexyl) - 5 - [3 - hydroxy - 4 - (3 - thienyloxy) - butyl] - 2 - pyrrolidone NMR =3.7 ppm (s) 3 protons =5.7 ppm (m) thiophene protons 3 protons IR 1685 cm-' vC=0 1730 cm-' vC=0 6. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 7,7,8,8,8 pentafluorooctyl) - 2 - pyrrolidone NMR =3.7 ppm (s) COOCH3 3 protons IR 1675 cm-1 vC=0 1730 cm-' vC=0 7. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 5 - cyclopentyl - 4,4 dimethylpentyl) - 2 - pyrrolidone NMR =0.9 ppm (s) C(CH3)2 6 protons =3.65 ppm (s) COOCH3 3 protons 8. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 5 - phenylpentyl) - 2 pyrrolidone NMR #=3.7 ppm (s) COOCH3 3 protons #7.3 ppm (s) C6H5 5 protons IR 1682 cm-' vC=0 1730 cm-1 #C=0 9. 1 - (6 - methoxycarbonylhexyl) - 5 - [3 - hydroxy - 5 - (4 - methyl - 2 ehlorophenyl - 4,4 - dimethylpentyl] - 2 - pyrrolidone Chromatography toluene/ethyl acetate 5:4 NMR 6=1.0 ppm (s) C(CH3)2 6 protons 6=2.25 ppm (s) CH3 3 protons #=@.1-@.5 ppm (m) aromatic protons- @ protons IR 1670 cm-1 #C=0 1735 cm-1 #C=0 10. 1 - (6 - ethoxycarbonylhexyl) - 5 - (3 - hydroxy - 7 - methyloctyl) - 2 pyrrolidone NMR 6=1.0 ppm (d) CH(CH3)2 6 protons 6=1.25 ppm (t) COOCH2CH3 3 protons IR 1685 cm-1 vC=0 1725 cm-1 #C=0 11. 1 - (6 - ethoxycarbonylhexyl) 5 - (3 - hydroxy - 4,4 - dimethyloctyl) - 2 pyrrolidone NMR 6=0.9 ppm (s) C(CH3)2 6 protons IR 1680 cm-1 vC=0 1735 cm-1 #C=0 12. 1 - (6 - ethoxycarbonylhexyl) - 5 - (3 - hydroxy - 4 - (3 trifluoromethylphenoxy) - butyl) - 2 - pyrrolidone NMR #=1.1 ppm (t) COOCH2CH3 3 protons #=7.1-7.4 ppm (m) aromatic protons 4 protons IR 1678 cm-' vC=0 1730 cm-1 #C=0 13. 1 - (6 - ethoxycarbonylhexyl) - 5 - [3 - hydroxy - 4 - (4 - chlorobenzyloxy) butyl] - 2 - pyrrolidone NMR 6=1.1 ppm (t) COOCH2CH3 3 protons #=7.0-7.5 ppm (m) aromatic protons 4 protons IR 1680 cm-1 #C=0 1735 cm-1 #C=0 14. 1 - (6 - ethoxycarbonylhexyl) - 5 - [3 - hydroxy - 4 - (2 - thienyl) - butyl] 2 pyrrolidone NMR #=7.1-7.3 ppm (m) thiophene protons 3 protons 6=1.1 ppm (t) COOCH2CH3 3 protons IR 1680 cm-1 vC=0 1740 cm-1 #C=0 15. 1 - (7 - ethoxycarbonylheptyl) - 5 - (3 - hydroxy - 5 - ethoxy - 4,4 dimethylpentyl) - 2 - pyrrolidone NMR 6=0.9 ppm (s) C(CH3)2 6 protons 6=1.2 ppm (t) COOCH2CH3 3 protons IR 1675 cm-' vC=0 1730 cm-' vC=0 16. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3 - methyloctyl) - 2 pyrrolidone NMR 6=1.3 ppm (s) C(CH3) 3 protons 6=3.7 ppm (s) COOCH3 3 protons IR 1680 cm-' vC=0 1735 cm-' vC=0 17. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3,4,4 - trimethyl - 5 ethoxypentenyl) - 2 - pyrrolidone NMR 6=0.9 ppm (s) C(CH3)2 6 protons 6=1.4 ppm (s) -CH3 3 protons 6=3.7 ppm (s) COOCH3 3 protons IR 1680 cm-' vC=0 1728 cm-' vC=0 18. 1 - (6 - methoxyearbonylhexyl) - 5 - (3 - hydroxy - 3 - benzyldecyl) - 2 pyrrolidone NMR #=7.1-7.3 ppm (m) C6H5 5 protons #=3.7 ppm (s) COOCH3 3 protons IR 1675 cm-1 #C=0 1730 cm-' vC=0 Example 2 a) (VIII) 5 - (3 - oxooctyl) - 2 - pyrrolidone The 5 - (3 - oxo - (E) - 1 - octenyl) - 2 - pyrrolidone is hydrogenated to form 5 - (3 - oxooctyl) - 2 - pyrrolidone as described in Example 1 No. 1.

The crude product is used for further reaction.

IR 1680 cm-1 vC=0 1705 cm-1 vC=0 not completely resolved absorptions b) (XIX) 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - oxooctyl) - 2 - pyrrolidone I mmol of 5 - (3 - oxooctyl) - 2 - pyrrolidone is dissolved in 10 ml of dimethylformamide, 1 mmol of sodium hydride is added and the whole is stirred for 1 1/2 hours at 50 C. After adding catalytic amounts of sodium iodide, 1.2 mmol of 6 - bromohexanoic acid methyl ester is dissolved in 5 ml of dimethylformamide is added and the whole is then kept for a further 5 hours at this temperature. Water is added for working-up, the whole is shaken several times with ether, the organic phases are purified, dried and concentrated.

Chromatography: carbon tetrachloride/acetone 7:3 NMR #=3.7 ppm (s) COOCH3 3 protons IR 1675 cm-1 #C=0 1705 cm-' vC=0 1740 cm-l vC=0 c) (I) 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3 - ethynyloctyl) - 2 pyrrolidone A solution of 10 mmol of 1 - (6 - methoxycarbonylhexyl) - 5 - (3 oxooctyl) - 2 - pyrrolidone in 70 ml of ether is cooled under nitrogen to -100C.

While stirring, 12 ml of a 1 molar solution of lithium acetylide in tetrahydrofuran is added and the whole is stirred for 30 minutes. -1.5 ml of a saturated ammonium chloride solution are then added at OOC. After approximately ten minutes, anhydrous magnesium chloride is added and suction filtering, concentration and chromatography are effected.

(SiO2: toluene/ethyl acete/methanol 5:4:0.1) NMR #=3.6 ppm (s) COOCH3 3 protons #=2.7 ppm (s) C=CH 1 proton IR 1735 cm-1 vC=0 1685 cm-' vC=0 Example 3 a) (VII) 1. 5 - (3 - oxodecyl) - 2 - pyrrolidone By hydrogenation of 5 - (3 - oxo - (E) - 1 - deceny!)- 2 - pyrrolidone according to Example 2a.

IR 1705 cm-' vC=0 1675 cm~1 vC=0 2. 5 - (3 - oxo - 4,4 - dimethyloctyl) - 2 - pyrrolidone By hydrogenation of 5 - (3 - oxo - (E) - 1 - octenyl) - 2 - pyrrolidone according to Example 2a.

NMR =1.05 ppm (s) C(CH3)2 6 protons IR 1700 cm-1 #C=0 1670 cm-1 #C=0 3. 5 - (3 - oxo - 4,4 - dimethyl - 5 - ethoxypentyl) - 2 - pyrrolidone By hydrogenation of 5 - (3 - oxo - 4,4 - dimethyl - 5 - ethoxy - (E) - I pentenyl) - 2 - pyrrolidone in a manner analogous to that in Example 2a.

NMR #=0.9 ppm (s) C(CH3)2 6 protons 1680 cm-1 #C=0 1710 cm-1 #C=0 4. 5 - [3 - oxo - 4 - (3 - trifluoromethylphenoxy) - butyl] - 2 - pyrrolidone By hydrogenation of 5 - [3 - oxo - 4 - (3 - trifluoromethylphenoxy) - (E) 1 - butenyl] - 2 - pyrrolidone in a manner analogous to that in Example 2a.

NMR =4.5 ppm (s) CH2 2 protons IR 1680 cm-' vC=0 1700 cm-' vC=0 The compounds synthesized under 1 to 4 are used as the crude products for further reactions. b) (IX) 1. 1 - allyl - 5 - (3 - oxodecenyl) - pyrrolidone - 2 2.5 mmol of 5 - (3 - oxodecyl) - 2 - pyrrolidone are dissolved in 15 ml of dimethyl sulfoxide (dried) and 3 mmol of potassium hydroxide are added. While cooling with ice, 3 mmol of allyl bromide dissolved in 3 ml of dimethyl sulfoxide are added dropwise. The whole is then stirred for 2 hours in the course of which the reaction solution comes up to room temperature. Water is added and the product is extracted with ether, the organic phases are combined, dried, concentrated and chromatographed.

Chromatographic separation takes place, as in the following 4 Examples, on silica gel with toluene/ethyl acetate 5:4 as the eluting agent: NMR S=5.6-6.2 ppm (m) CH=CH2 3 protons IR 1700 cm-1 #C=0 1685 cm-1 <RT 2. 1 - allyl - 5 - (3 - oxo - 4,4 - dimethyloctyl) - 2 - pyrrolidone By alkylation of 5 - (3 - oxo - 4,4 - dimethyloctyl) - 2 - pyrrolidone with allyl bromide in a manner analogous to that in Example 3 b 1.

NMR ô=5.06.2 ppm (m) CH=CH2 3 protons o=1.05 ppm (s) C(CH3)2 6 protons IR 1705 cm-1 vC=0 1675 cm-1 #C=0 3. 1 - allyl - 5 - (3 - oxo - 4,4 - dimethyl - 5 - ethoxypentyl) - 2 - pyrrolidone By alkylation of 5 - (3 - oxo - 4,4 - dimethyl - 5 - ethoxy - pent - 1 - yl) pyrrolidone - 2 with allyl bromide in a manner analogous to that in Example 3 b 1.

NMR o=0.9 ppm (s) C(CH3)2 6 protons #=5.0-6.2 ppm (m) CH=CH2 3 protons IR 1680 cm-' vC=0 1705 cm-1 #C=0 4. 1 - allyl - 5 - [3 - oxo - 4 - (3 - trifluoromethylphenoxy) - butyl] - 2 pyrrolidone By alkylation of 5 - [3 - oxo - 4 - (3 - trifluoromethylphenoxy) - butyl] - 2 pyrrolidone with allyl bromide in a manner analogous to that in Example 3 b 1.

NMR 8=4.5 ppm (s) CH2 2 protons #=5.0-6.2 ppm (m) CH=CH2 3 protons 8=7.1-7.4 ppm (m) aromatic protons 4 protons IR 1680 cm-1 vC=0 1700 cm-' vC=0 5. 1 - allyl - 5 - (3 - oxooctyl) - 2 - pyrrolidone By alkylation of 5 - (3 - oxooctyl) - 2 - pyrrolidone with allyl bromide in a manner analogous to that in Example 3 b 1.

NMR 8=5.0-6.2 ppm (m) CH=CH2 3 protons IR 1700 cm-' vC=0 1675 cm-' vC=0 e) (X) 1. 1 - formylmethyl - 5 - (3 - oxodecyl) - 2 - pyrrolidone 0.02 mol of 1 - alkyl - 5 - (3 - oxodecyl) - 2 - pyrrolidone - 2 is dissolved in 100 ml of methylene chloride and 10 ml of methanol are added. The whole is cooled to -780C and ozone is introduced at this temperature until the blue solution no longer becomes decolorized. The reaction mixture is heated to -20 C. At this temperature 0.2 mol of dimethyl sulfide are added dropwise. The cooling bath is removed and the reaction flask is left for two hours at room temperature.

The whole is concentrated and chromatographed.

(Silica gel: chloroform, acetone 8:2) NMR =9.6 ppm CHO 1 proton The following l-formylmethyl compounds are prepared by ozonolysis from the l-allyl compounds, as described above.

2. 1 - formylmethyl - 5 - (3 - oxo - 4,4 - dimethyloctyl) - 2 - pyrrolidone chromatography chloroform/acetone 8:2 NMR 8=9.6 ppm CHO 1 proton 3. 1 - formylmethyl - 5 - (3 - oxo - 4,4- dimethyl - 5 - ethoxypentyl)- 2 pyrrolidone chromatography: carbon tetrachloride/acetone 7:3 NMR 8=9.5 ppm CHO 1 proton 8=0.9 ppm C(CH3)2 6 protons 4. 1 - formylmethyl - 5 - [3 - oxo - 4 - (3 - trifluoromethylphenoxy) - butyl] - 2 pyrrolidone chromatography chloroform/acetone 8:2 NMR #=4.4 ppm (s) CH2 2 protons #=7.1-7.4 ppm (m) aromatic protons 4 protons 6=9.3 ppm CHO 1 proton 5. 1 - formylmethyl - 5 - (3 - oxooctyl) - 2 - pyrrolidone chromatography: chloroform/ethyl acetate 4:1 NMR a=9.6 ppm CHO 1 proton d) (XII) 1. 1 - (6 - carboxy - (7) - 2 - hexenyl) - 5 - (3 - oxodecyl) - 2 - pyrrolidone 0.01 mol of sodium hydride is stirred in 5 ml of dimethyl sulfoxide at 600C until the evolution of hydrogen is complete. The whole is then cooled to room temperature and 5 mmol of 4 - carboxybutyl - triphenylphosphonium bromide dissolved in 5 ml of dimethyl sulfoxide are added. The whole is stirred for 30 minutes at room temperature. 2 mmol of 1 - formylmethyl - 5 - (3 - oxodecyl) 2 - pyrrolidone dissolved in 3 ml of dimethyl sulfoxide are then added and the whole is subsequently heated to 500 C. Stirring is effected for three hours at this temperature. After cooling, 40 ml of.water are added and the pH value is adjusted to 2 with a 5% strength solution of sodium hydrogen sulfate. Extraction with ether. drying and concentration are effected. chromatography: chloroform/methanol 95:5 NMR =5.2-5.7 ppm (m) CH=CH 2 protons The following four 1 - (6 - carboxy - (Z) - 2 - hexenyl) compounds are prepared, as described above, from the corresponding 1 - formylmethyl compounds by Wittig reaction with (4 - carboxybutylidene) triphenylphosphorane.

2. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - oxo - 4,4 - dimethyloctyl) - 2 pyrrolidone chromatography: toluene/ethyl acetate/glacial acetic acid 5:4:0.0 NMR =5.3-5.5 ppm (m) CH=CH 2 protons ô=1.05 ppm (s) C(CH3)2 6 protons 3. 1 - (6 - carboxy - (7) - 2 - hexenyl) - 5 - (3 - oxo - 4,4 - dimethyl - 5 ethoxy - pentyl) - 2 - pyrrolidone chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.3-5.5 ppm (m) CH=CH 2 protons ô=0.9 ppm (s) C(CH3)2 6 protons 4. 1 - (6 - carboxy - (Z)- 2- hexenyl) - 5 - [3 - oxo - 4(3 trifluoromethylphenoxy) - butyl - 2 - pyrrolidone chromatography: chloroform/methanol 95.5 NMR #=5.1-5.2 ppm (m) CH=CH 2 protons 8=7.1-7.4 ppm (m) aromatic protons 4 protons 8=4.4 ppm (s) CH2 2 protons 5. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - oxooctyl) - 2 pyrrolidone chromatography: ethyl acetate/glacial acetic acid 98:2 NMR 8=5.2-5.5 ppm (m) CH=CH 2 protons 6. 1 - 5 - carboxy - (Z) - 2 - pentenyl) - 5 - (3 - oxooctyl) - 2 - pyrrolidone From 1 - formylmethyl - 5 - (3 - oxoctyl) - 2 - pyrrolidone and (3 carboxypropylidenetriphenylphosphorane according to Example 3 d 1. chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.1-5.3 ppm (m) CH=CH 2 protons 7. 1 - (7 - carboxy - (Z) - 2 - heptenyl) - 5 - (3 - oxooctyl) - 2 - pyrrolidone From 1 - formylmethyl - 5 - (3 - oxooctyl) - 2 - pyrrolidone - 2 and (5 carboxypentylidene)triphenylphosphorane according to Example 3 d 1.

Chromatography: ethyl acetate/toluene/glacial acetic acid 4:5:0.01 NMR #=5.2-5.4 ppm (m) CH=CH 2 protons e) (I) 1. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - hydroxydecyl) - 2 - pyrrolidone 4 mmol of anhydrous zinc chloride are suspended in 10 ml of 1,2 dimethoxyethane and 16 mmol of sodium borohydride are carefully added. The whole is then stirred for one hour at room temperature. Filtering off is effected and 0.8 mmol of I - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - oxodecyl) - 2 pyrrolidone dissolved in 2 ml of dimethoxyethane are added dropwise within 10 minutes to the solution thus obtained and the whole is then stirred for 2 1/2 hours at room temperature. Acidification with glacial acetic acid, concentration and chromatography are effected (silica gel: ethyl acetate/glacial acetic acid 98:2).

NMR #=5.3-5.5 ppm (m) CH=CH 2 protons IR 1680 cm-1 #C=0 1700 cm-1 #C=0 #3200 cm-1 broad absorption #O-H The following compounds indicated under 2 to 7 are produced from the basic ketones by reduction as described under 1). Chromatographic purification is, in these cases, effected exclusively on silica gel with ethyl acetate/glacial acetic acid 98:2.

2. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - hydroxy - 4,4 - dimethyloctyl) 2 - pyrrolidone NMR #=5.2-5.4 ppm (m) CH=CH 2 protons â=0.95 ppm (s) C(CH3)2 6 protons 3.1 - (6 - carboxy - (Z) - 2 - hexen - 1 - yl) - 5 - (3 - hydroxy - 4,4 - dimethyl 5 - ethoxypentyl) - 2 - pyrrolidone NMR #=5.1-5.3 ppm (m) CH=CH 2 protons ô=0.9 ppm (s) C(CH3)2 6 protons ô=l.l ppm (t) OCH2CH3 3 protons 4. 1 - (6 - carboxy - (Z)- 2 - hexenyl) - 5 - [3 - hydroxy - 4 - (3 - trifluoromethylphenoxy) - butyl] - 2 - pyrrolidone NMR #=5.1-5.25 ppm (m) CH=CH 2 protons #=4.4 ppm (d) CH2 2 protons #=7.2-7.4 ppm (m) aromatic protons 4 protons 5. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone NMR #=5.2-5.4 ppm (m) CH=CH 2 protons

IR 1680 cm-' A vC=0 absorptions not completely resolved.

1700 cm-1 # 6. 1 - (5 - carboxy - (Z) - 2 - pentyl) - 5 - (3 - hydroxyoct - 1 - yl) - 2 pyrrolidone NMR #=5.2-.4 ppm (m) CH=CH 2 protons 1680 cm-' vC=0 1700 cm-1 #C=0 7. 1 - (7 - carboxy - (Z) - 2 - heptenyl) - 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone NMR #=5.25-5.4 ppm (m) CH=CH 2 protons IR broad absorption at 16801700 cm-' vC=0 8. 1 - (6 - carboxy - (Z) - hexenyl) - 5 - (3 - hydroxy - 3 - methyloctyl) - 2 pyrrolidone From the compound of Example 3 b 5 by reaction with methyl-magnesium iodine in a manner analogous to that in Example 2 c.

Chromatography: toluene/ethyl acetate/glacial acetic acid 50:50:2 NMR ô=2.3 ppm (s) CH3 3 protons #=5.2-5.4 ppm (m) CH=CH 2 protons 9. 1 - (6 - carboxy - (Z) - hexenyl) - 5 - [3 - hydroxy - 3 - (allyloctyl] - 2 pyrrolidone From the compound of Example 3 b 5 by reaction with allylmagnesium bromide in a manner analogous to that in Example 2 c.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR ô=5.W6.2 ppm (m) CH=CH and 5 protons CH=CH, IR 1680 cm-1 and 1700 cm-' the two absorption maxima not clearly resolved (vC=0) 10. 1 - (6 - methoxycarbonyl - (Z) - 2 - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 pyrrolidone 1 mmol of 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 pyrrolidone is dissolved in 10 ml of 0.1 normal aqueous sodium hydroxide solution and the solvent is then concentrated. The remaining traces of water are removed under high vacuum. 8 ml of acetonitrile and 10 ml mol of methyl iodide are added and the whole is boiled for five hours under reflux. The reaction solution is distributed between water and ether, and the organic phase is dried, concentrated and chromatographed.

Eluting agent: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=3.7 ppm (s) COOCH3 3 protons #=5.2-5.35 ppm (m) CH=CH 2 protons IR 1680 cm-' vC=0 1735 cm-1 #C=0 11. 1 - (6 - n - hexyloxycarbonyl - (Z) - 2 - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 pyrrolidone Analogously to the above instructions from 1 - (6 - carboxy -(Z)- 2 hexenyl) - 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone and n - hexyl bromide.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.1 NMR - a=5.2-5.35 ppm (m) CH=CH 2 protons #=4.2-4.4 ppm (t) diffused COOCH2- 2 protons signals fi (I) 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone By hydrogenation of I - (6 - methoxycarbonyl - (Z) - 2 - hexenyl) - 5 - (3 hydroxyoctyl) - 2 - pyrrolidone analogously to Example 1. The physical data correspond to those of Example 1 No. 1. g) (XVII) 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone By reduction of 5 - (3 - oxooctyl) - 2 - pyrrolidone with zinc borohydride analogously to Example 3 e 1.

Chromatography: chloroform/methanol 95:5 IR 1780 cm-' vC=0 MS M# = 213 h) (I) 1. 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone From 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone by alkylation with 6 - bromo (Z)- 4 - hexene - 1 - carboxylic acid analogously to Example 3 b 1. The chromatographic conditions and physical-chemical data corresponding to Example 3 e 5.

2. 1 - (6 - carboxy - (E) - hexenyl) - 5 - (3 - hydroxyoctyl) - 2 pyrrolidone From 5 - (3 - hydroxyoctyl) - 2 - pyrrolidone by alkylation with 6 - bromo (E) - 4 - hexene - 1 - carboxylic acid analogously to Example 3 b 1.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.1-5.35 ppm CH=CH 2 protons IR 1680 cm-1 and 1700 cm-' the two absorption maxima for vC=0 not completely resolved 3. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxyoct - 1 - yl) - 2 - pyrrolidone From 5- (3 - hydroxyoctyl)- 2- pyrrolidone by alkylation with 6bromohexanecarboxylic acid analogously to Example 2 b.

Chromatography: ethyl acetate/glacial acetic acid 98:2 Revalue: 0.25 i) (XIII) 5 - [3 - (tetrahydropyran - 2 - yl - oxy) - 3 - methyloctyl] - 2 - pyrrolidone By hydrogenation of 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyl (E) - 1 - octenyl] - 2 - pyrrolidone according to the instructions given in Example 1, No. 1.

Chromatography: chloroform/ethyl acetate/methanol 5:4:0.5 NMR #=4.65 ppm broad O-CH-O 1 proton singlet ô=2.1 ppm (s) CH3 3 protons IR 1680 cm-' vC=0 k) (XIV) 1 - allyl - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyloctyl] - 2 pyrrolidone From 5 - [3 - (tetrahydropyran - 2- yloxy) - 3 - methyloctyl] - 2pyrrolidone by alkylation with allyl bromide analogously to Example 3 b 1.

Chromatography: carbon tetrachloride/acetone 7:3 NMR #5.2-6.0 ppm (m) CH=CH2 3 protons #4.65 ppm broad O-CH-O 1 proton singlet ô=2.05 ppm (s) CH3 3 protons IR 1680 cm-' vC=0 l) (xv) 1 - formylmethyl - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyloctyl] - 2 pyrrolidone From 1 - allyl - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyloctyl] - 2 pyrrolidone by ozonolysis analogous to Example 3 c 1.

Chromatography: toluene/ethyl acetate 5:4 NMR ô=9.6 ppm (s) CHO I proton #=4.6 ppm broad O-CH-O 1 proton singlet #=2.05 ppm . (s) (s) CH3 3 protons m) (XVI) I - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 methyloctyl] - 2 - pyrrolidone Analogous to Example 3 d 1 from 1 - formylmethyl - [3 - (tetrahydropyran 2 - yloxy) - 3 - methyloctyl] - 2 - pyrrolidone and the 4 carboxybutylidene)triphenylphosphorane.

Chromatography: toluene/ethyl acetate/glacial acetic acid 5:4:0.02 NMR 8=5.2-5.5 ppm (m) CH=CH 2 protons 8=4.65 ppm broad O-CH-O 1 proton singlet n) (I) 1 - (6 - carboxy (7) - 2 - hexenyl) - 5 - (3 - hydroxy - 3 - methyloctyl) - 2 pyrrolidone 0.05 mol of 1 - (6 - carboxy - (Z) - 2 - hexenyl) - 5 - [3 - (tetrahydropyran 2 - yloxy) - 3 - methyloctyl] - 2 - pyrrolidone is stirred in a mixture of 20 ml of ethanol and 10 ml of 6% strength aqueous oxalic acid for 4 hours at room temperature and then stirred for 4 hours at 40-45 C. The reaction mixture is then divided between ether and water and the aqueous phase is extracted several times with ether, the organic phase is dried and concentrated and the residue chromatographed.

For chromatographic conditions and physical-chemical properties see Example 3 e 8.

Example 4 a) (IV) The compounds given under 1 to 9 are produced from the starting materials indicated in each case according to the instructions given in Example 2 b. When alkylating with an acid, the appopriate additional amount of sodium hydride must be used for neutralization of the acid.

1. 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - (E)- 1 - decenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy) - (E) - decenyl] - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid.

Chromatography: ethyl acetate/toluene/methanol 4:5:0.2 NMR 8=4.4 ppm broad singlet O-CH-O 1 proton 8=5.1-5.4 ppm (m) CH=CH 2 protons 2. 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 4,4 - dimethyl (E) - 1 - octenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy)- 4,4 - dimethyl - (E) - I octenyl] - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=1.0 ppm (s) C(CH3)2 6 protons #=5.2-5.4 ppm (m) CH=CH 2 protons 8=4.5 ppm broad singlet O-CH-O 1 proton 3. 1 - (6 - carboxyhexyl) - 5 - [5 - (tetrahydropyran - 2 - yloxy) - 5 - phenyl - (E) - 1 - pentenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy) - 5 - phenyl - (E) - I pentenyl] - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid.

Chromatography: carbon tetrachloride/acetone 7:3 NMR ô=4.4 ppm broad signal O-CH-O I proton #=5.2-5.35 ppm (m) CH=CH 2 protons ô=7.3 ppm (s) C6H5 5 protons 4. 1 - (5 - carboxypentyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - (E) - I octenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2- yloxy)- (E)- 1 - octenyl] - 2 pyrrolidone and 5 - bromopentanecarboxylic acid.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR ô=4.35ppmbroad signal O-CH-O 1 proton #=5.3-5.45 ppm (m) CH=H 2 protons 5. 1 - (7 - carboxyheptyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - (E) - I octenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2- yloxy)- (E) - I - octenyl] - 2 pyrrolidone and 7 - bromoheptanecarboxylic acid.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR ô=4.40 ppm broad singlet O-CH-O I proton #=5.25-5.40 ppm (m) CH=CH 2 protons 6. 1 - (6 - methoxycarbonylhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 4,4 dimethyl - 5 - ethoxy - (E) - pentenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy) - 4,4 - dimethyl - 5 - ethoxy (E) - 1 - pentenyl] - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid methyl ester.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=0.9 ppm (s) C(CH3)3 6 protons ô=3.7 ppm (s) COOCH3 3 protons #=5.2-5.4 ppm (m) CH=CH 2 protons IR 1680 cm-1 #C=0 1730 cm-1 #C=0 7.1 - (6 - methoxycarbonylhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3,4,4 trimethyl - 5 - ethoxy - (E) - 1 - pentenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy)3,4,4 - trimethyl - 5 -. ethoxy (E) - 1 - pentenyl] - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid methyl ester.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=3.7 ppm (s) COOCH3 3 protons #=0.95 ppm (s) C(CH3)3 6 protons #=4.45 ppm broad signal -O-OH-O- 1 proton IR 1680 cm-' #C=0 1735 cm-1 #C=0 8. 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyl - (E) - 1 - octenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyl - (E) - 1 - octenyl] 2 - pyrrolidone and 6 - bromohexanecarboxylic acid.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR ô=1.95 ppm (s) CH3 3 protons #=5.2-5.45 ppm (m) CH=CH 2 protons 9. 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - allyl - (E) 1 - octenyl] - 2 - pyrrolidone From 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - allyl - (E) - 1 - octenyl] 2 - pyrrolidone and 6 - bromohexanecarboxylic acid.

Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.2-6.0 ppm (m) CH=CH, CH=CH2 5 protons #=4.45 ppm (s, broad) O-CH-O 1 proton b) (I) The compounds indicated under 1 to 9 are, unless otherwise stated, produced by splitting off the THP protective group from the compounds indicated in Example 4 a under I to 9 analogously to the instructions given in Example 3 n.

1. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxy - (E) - 1 - decenyl) - 2 - pyrrolidone Chromatography: ethyl acetate/toluene/glacial acetic acid 4:5:0.02 R,=0.3 NMR #=5.1-5.4 ppm (m) CH=CH 2 protons 2. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxy - 4,4 - dimethyl - (E)- 1 -. octenyl) - 2 - pyrrolidone Chromatography: ethyl acetate/glacial acetic acid. 98:2 NMR #=1.0 ppm (s) C(CH3)2 6 protons #=5.2-5.4 ppm (m) CH=CH 2 protons 3. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxy - 5 - phenyl - (E) - 1 - pentenyl) - 2 pyrrolidone Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.2-5.35 ppm (m) CH=CH 2 protons #=7.3 ppm (s) C6H5 5 protons 4. 1 - (5 - carboxypentyl) - 5 - (3 - hydroxy - (E) - I - octenyl) - 2 - pyrrolidone Chromatography: ethyl acetate/glacial acetic acid 98:2 Rf=0.35 NMR #=5.3-5.45 ppm (m) CH=CH 2 protons 5. 1 - (7 - carboxyheptyl) - 5 - (3 - hydroxy - (E) - I - octenyl) - 2 - pyrrolidone Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR =5.25-5.40 ppm (m) CH=CH 2 protons IR 1680 cm-1-1705cm-1 unresolved absorption of two #C=0 6. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 4,4 - dimethyl - 5 - ethoxy - (E) - I - pentenyl) - 2 - pyrrolidone As a departure from the instructions given in Example 3 n, a 1% w/v solution of oxalic acid in methanol is used as the solvent instead of aqueous/ethanolic oxalic acid.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=0.9 ppm (s) C(CH3)3 6 protons ô=3.7 ppm (s) COOCH3 3 protons #=5.2-5.4 ppm (m) CH=CH 2 protons IR 1680 cm-1 #C=0 1735 cm-1 #C=0 7. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3,4,4 - trimethyl - 5 - ethoxy - (E) - 1 - pentenyl) 2 - pyrrolidone Splitting off the ether protective group as described above.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=3.7 ppm (s) COOCH3 3 protons #=0.95 ppm (s) C(CH3)3 @ protons IR 1685 cm-1 #C=0 1735 cm-1 #C=0 8. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxy - 3 - methyl - (E) - 1 - octenyl) - 2 pyrrolidone Chromatography: ethyl acetate/glacial acetic acid. 98:2 Rf=0.35 NMR ô=1.95 ppm (S) CH3 3 protons #=5.25-5.40 ppm (m) CH=CH 2 protons 9.1 - (6 - carboxyhexyl) - 5 - [3 - hydroxy - 3 - allyl - (E) - 1 - octenyl] - 2 pyrrolidone Chromatography: ethyl acetate/glacial acetic acid 98:2 NMR #=5.2-6.0 ppm (m) CH=CH, CH=CH2 5 protons IR 1680-1705 cm-1 broad absorption two unresolved #C=0 c) (I) 1. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3 - methyloctyl) - 2 pyrrolidone Analogous to Example 1, no. I by hydrogenation of 1 - (6 - carboxyhexyl) 5 - (3 - hydroxy - 3 - methyl - (E) - 1 - octenyl) - 2 - pyrrolidone and subsequent esterification with diazomethane. Physical data and chromatographic conditions of Example 1, No. 16.

2. 1 - (6 - carboxyhexyl) - 5 - (3 - hydroxydecyl) - 2 - pyrrolidone Analogous to Example 1 by hydrogenation of 1 - (6 - carboxyhexyl) - 5 - (3 hydroxy - (E) - 1 - decenyl) - 2 - pyrrolidone.

Chromatography: ethyl acetate/toluene 5:5:0.02 R,=0.33 d) (VI) 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - oxo - 4,4 - dimethyl - 5 - ethoxy - (E) 1 - pentenyl) - 2 - pyrrolidone From 5 - (3 - oxo - (E) - 1 - pentenyl) - 4,4 - dimethyl - 5 - ethoxy - (E) I - pentenyl) - 2 - pyrrolidone and 6 - bromohexanecarboxylic acid methyl ester analogously to Example 2 b.

Chromatography: toluene/ethyl acetate/methanol 5:4:0.3 NMR ô=0.9 ppm (s) C(CH3)3 6 protons ô=3.7 ppm (s) COOCH3 3 protons #=5.5-6.2 ppm (m) CH=CH 2 protons IR 1680 cm-1 #C=0 e) (I) 1. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 4,4 - dimethyl - 5 ethoxy - (E) - I - pentenyl) - 2 - pyrrolidone By reduction of the compound described under d) with zinc borohydride analogous to Example 3 e 1. For physical-chemical data see Example 4 b 6.

2. 1 - (6 - methoxycarbonylhexyl) - 5 - (3 - hydroxy - 3,4,4 - trimethyl - 5 ethoxy - (E) - I - pentenyl) - 2 - pyrrolidone By reaction of the compound mentioned under 4 d) with methyl-magnesium iodide analogous to Example 2 c.

Physical-chemical data of Example 4 b 7. f) (VII) 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 - methyloctyl] 2 - pyrrolidone From 1 - (6 - carboxyhexyl) - 5 - [3 - (tetrahydropyran - 2 - yloxy) - 3 methyl - (E) - 1 - octenyl] - 2 - pyrrolidone by hydrogenation analogous to Example 1, No. 1.

Chromatography; toluene/ethyl acetate/methanol 5:4:0.1 NMR ô=4.4 ppm (s, spread) O-CH-O g) (I) 1 - (6 - methoxycarbonylhexyl) - S - (3 - hydroxy - 3 - methyloctyl) - 2 pyrrolidone From the compound described under 4 f) by splitting off the THP protective group and simultaneously esterifying the carboxy group analogously to Example 4 b 6 except that p-toluene-sulphonic acid is used as the catalyst instead of oxalic acid. Physical-chemical data of Example 1, No. 16.

Claims

WHAT WE CLAIM IS:-

1. A compound of the general formula I

in which R1 represents a straight or branched chain, saturated or unsaturated, aliphatic hydrocarbonyl radical having up to 10 carbon atoms or a cycloaliphatic hydrocarbyl radical having 3-7 carbon atoms, which radicals can each be substituted by a) a straight chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 5 carbon atoms, b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1--3 carbon atoms, halogen atoms, phenoxy radicals, and alkoxy radicals having 14 carbon atoms, which alkyl and phenoxy groups may be substituted by one or more halogen atoms, c) a furyloxy, thienyloxy or benzyloxy radical each of which may be monosubstituted or disubstituted in the ring by one or two substituents selected, independently in the latter case, from halogen atoms, alkyl groups having 1--3 carbon atoms which may be substituted by one or more halogen atoms, and alkoxy groups having 1 to 4 carbon atoms, d) a trifluoromethyl group or a pentafluoroethyl group, e) a cycloalkyl radical having 3-7 carbon atoms, f) a phenyl, thienyl, or furyl radical each of which may be monosubstituted or disubstitued by one or two substituents selected, independently in the latter case, from halogen atoms, alkyl groups having 1--3 carbon atoms which may be substituted by one or more halogen atoms, and alkoxy groups having 14 carbon atoms, R2 represents a straight or branched chain, saturated or unsaturated, aliphatic or cycloaliphatic hydrocarbon radical having 2-6 carbon atoms, an araliphatic hydrocarbon radical having 7 or 8 carbon atoms or, if R1, R3, A, B and n do not simultaneously represent a hydrogen atom, an n-pentyl group, a -CH2-CH2- group, a -CH=CH- group and the integer three respectively, a methyl group or a hydrogen atom, R3 represents a hydrogen atom or a straight or branched chain alkyl, alkenyl, or alkynyl radical having up to 5 carbon atoms or an araliphatic hydrocarbon radical having 7 or 8 carbon atoms, A and B each represents a -CH2-CH3- or a -CH=CH- group, wherein A and B may be the same or different but may not simultaneously be a -CH=CH- group, n represents the integer two, three or four.

2. A compound as claimed in claim 1, wherein R1 represents a straight or branched chain, saturated or unsaturated, aliphatic hydrocarbon radical having up 'to 7 carbon atoms or a cycloaliphatic hydrocarbon radical having 5 to 7 carbon atoms, which radicals can each be substituted by a) a straight or branched chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 4 carbon atoms b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1-3 carbon atoms, methoxy and ethoxy groups, trifluoromethyl groups, halogen atoms, and phenoxy radicals which may be substituted by one or more halogen atoms, c) a thienyloxy or benzyloxy radical, each of which may be monosubstituted or disubstituted in the ring by one or two substituents selected, independently in the latter case, from alkyl groups having 1--3 carbon atoms, trifluoromethyl groups, halogen atoms, methoxy and ethoxy groups. d) a trifluoromethyl group, e) a cycloalkyl radical having 5-7 carbon atoms, f) a phenyl radical or thienyl radical each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from alkyl groups having 1--3 carbon atoms, trifluoromethyl groups, halogen atoms, methoxy and ethoxy groups.

R2 represents a straight or branched chain alkyl radical having 1--6 carbon atoms, a straight or branched chain alkenyl radical having 24 carbon atoms, a cycloalkyl radical having 5 or 6 carbon atoms or an aralkyl radical having 7 or 8 carbon atoms, R3 represents a hydrogen atom, a straight or branched chain alkyl radical having 1 to 5 carbon atoms, an alkenyl radical or alkynyl radical having 2 to 5 carbon atoms.

3. A compound as claimed in Claim 2, wherein R1 represents a straight or branched chain alkyl radical having 1--7 carbon atoms, a straight or branched chain alkenyl radical having 3-5 carbon atoms or a cycloalkyl radical having 5-7 carbon atoms, which radicals may be substituted by: a) a straight or branched chain alkoxy, alkylthio, alkenyloxy or alkenylthio radical having up to 3 carbon atoms, b) a phenoxy radical which may itself be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, and phenoxy radicals optionally substituted by chlorine and/or fluorine atoms, c) a thienyloxy or benzyloxy radical each of which may be monosubstituted or disubstituted in the nucleus by one or two substituents selected, independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, d) a trifluoromethyl group, e) a cycloalkyl radical having 5-7 carbon atoms, f) a phenyl radical or thienyl radical each of which may be monosubstituted or disubstituted by one or two substituents selected, independently in the latter case, from methyl, trifluoromethyl and methoxy groups, chlorine and fluorine atoms, R2 represents a straight-chain alkyl radical having 1 to 6 carbon atoms, a branched chain alkyl radical having 3-5 carbon atoms, a straight chain alkenyl radical having 24 carbon atoms, a cyclopentyl or cyclohexyl radical or a benzyl radical, R3 represents a hydrogen atom, a methyl, ethyl or propyl radical or an alkenyl or alkynyl radical having 2 or 3 carbon atoms, and n represents the integer 3.

4. A compound as claimed in Claim 1 and which is named in Table I herein.

5. A compound as claimed in Claim 1 and which is described in any one of the Examples herein.

6. A salt of a free acid as claimed in any one of Claims 1 to 5.

7. A physiologically tolerable salt of a free acid as claimed in any one of Claims 1 to 5.

8. A process for the production of a compound of the general formula I, as claimed in Claim 1, wherein al) a compound of formula II

wherein R1 and R3 have the meanings given in Claim 1 and R4 represents a protective group that can be split off under acidic conditions, is deprotonated at the nitrogen atom with a base and the anion thus formed is reacted with a carboxylic derivative of formula III Y-CH2-CH2-CH2-(CH2)n-COOR2 III wherein R2 and n have the meanings given in Claim 1 and Y represents a halogen atom, an alkanesulphonyloxy radical or a benzene sulphonyloxy radical that may be substituted by one or more substituents selected from alkyl groups and halogen atoms, to form a compound of formula IV

a2) the hydroxy protective group R4 is split off from the compound of formula IV by acid hydrolysis to form a compound of formula I in which A represents a -CH2-CH2- group and B represents a -CH=CH- group, or a2.1) a compound of formula V is reacted as described under a1) to form a compound of formula VI

wherein R1, R2 and n have the meanings given in Claim I, a2 2) the exocyclic carbonyl group in the compound of formula VI is reduced or the compound of formula VI is reacted with an organometallic compound produced from R3-X#, wherein X# represents a halogen atom, R3 has the meaning given in Claim 1 but cannot be hydrogen, to form a compound of formula I wherein A represents a -CH2-CH2- group and B represents a a -CH=CH- group, and optionally a3) a compound of formula I in which A represents a -CH2-CH2- group and B represents a -CH=CH- group, is hydrogenated to give a compound of formula I wherein A and B each represents a -CH3-CH3- group, or a3l) a compound of formula IV is hydrogenated to form a compound of formula VII

wherein R', R2, R3 and n have the meanings given in Claim 1 and R4 is as defined above and a3 2) the hydroxy protective group in the compound of formula VII is split off by acid hydrolysis to form a compound of formula I wherein A and B each represents a -CH2-CH3- group, or b1,1) in a compound of formula V

the double bond is hydrogenated to give a compound of formula VIII wherein R1 has the meaning given in Claim 1

b1.2) the compound of formula VIII is deprotonated at the nitrogen with a base and the anion formed is reacted with an allyl halide to form a compound of formula IX

wherein RI has the meaning given in Claim 1, bl3) the compound of formula IX is subjected to ozonolysis whereby an aldehyde of formula X is formed

wherein R' has the meaning given in Claim 1, b, 4) the aldehyde of formula X is reacted with an ylide of formula XI (R5)3P=CH(CH2)nCOOR2 XI wherein n and R2 have the meanings given in Claim 1 and R2 may also represent an alkali metal cation, the symbols R5 each represents the same or different straight chain (C1-C4)-alkyl radical or phenyl radical, to form a compound of formula XII

wherein R1, R2 and n have the meanings given in Claim.l, b1.5) the exocyclic carbonyl group of the compound of formula XII is reacted with an organometallic compound produced from R3-X#, wherein X# represents a halogen atom and R3 has the meaning given for formula I but may not be hydrogen, or the exocyclic carbonyl group in the compound of formula XII is reduced to form a compound of formula I wherein A represents a a -CH=CH- group and B represents a -CH2-CH2- group, or b2 l) the double bond in a compound of formula II is hydrogenated to form a compound of formula XIII

wherein R1 and R3 have the meanings given in Claim 1, and R4 is as defined above, b2.2) the compound of formula XIII is deprotonated at the nitrogen with a base and the anion formed is reacted with an allyl halide to form a compound of formula XIV

wherein R1 and R3 have the meanings given in Claim 1, and R4 is as defined above, b23) the compound of formula XIV is subjected to ozonolysis whereby an aldehyde of formula XV is formed

wherein R1 and R3 have the meanings given for formula I and R4 is as defined above, b3A) the aldehyde of formula XV is reacted with an ylide of formula XI (R5)3P=CH(CH2)nCOOR2 XI wherein n and R2 have the meanings given in Claim 1 and R2 may also represent an alkali metal cation and the symbols R5 are as defined above, to form a compound of formula XVI

wherein R1, R2, R3 and n have the meanings given for formula I and R4 is as defined above, b2 5) the protective group R4 is split off from the compound of formula XVI by acid hydrolysis to form a compound of formula I wherein A represents a -C=CH- group and B represents a -CH3-CH3- group, and optionally b3) a compound of formula I, wherein A represents a -CH=CH- group and B represents a -CH3-CH3- group, is hydrogenated to form a compound of formula I wherein A and B each represent a -CH3-CH2- group, or b4,1) the exocyclic carbonyl group in the compound of formula VIII is reduced, or the compound of formula VIII is reacted with an organo-metallic compound produced from R3-X#, wherein X# represents a halogen atom and R3 has the meaning given in Claim 1 but cannot represent hydrogen, to form a compound of formula XVII

wherein R1 and R3 have the meanings given in Claim 1 and b4 2) the compound of formula XVII is deprotonated at the nitrogen with a base and the anion formed is reacted with a carboxylic acid derivative of formula XVIII

wherein R2, A and n have the meanings given in Claim 1 and Y is as defined above to form a compound of formula I wherein A represents a -CH2-CH2-, or a -CH=CH- group and B represents a -CH2-CH2- group, or c1) a compound of formula VIII is deprotonated at the nitrogen with a base and the anion formed is reacted with a carboxylic acid derivative of formula III to form a compound of formula XIX

wherein R1, R2 and n have the meanings given in Claim I and c2) the exocyclic carbonyl group of the compound of formula XIX is reduced or the compound of formula XIX is reacted with an organometallic compound produced from R3-X#, wherein X# represents a halogen atom and R3 has the meaning mentioned in Claim 1 but cannot represent hydrogen, to form a compound of formula I wherein A and B each represent a -CH3-CH2- group, or d) a compound of formula XX

is hydrogenated, whereby a compound of formula I is formed, wherein A and B each represent a -CH2-CH3- group, or e) any one or more of the steps defined above is carried out analogously using a reactant analogous to a compound as defined above but in which a free hydroxyl group is present instead of a group OR4, or a group OR4 is present instead of a free hydroxyl group, as appropriate, R4 being as defined above, and f) if desired, a compound of formula I resulting from any of the above reactions is converted into a salt thereof.

9. A process as claimed in Claim 8, carried out substantially as described in any one of the Examples herein.

10. A compound as claimed in Claim I, whenever produced by a process as claimed in Claim 8 or Claim 9.

I 1. A pharmaceutical preparation which comprises a compound as claimed in any one of Claims 1 to 5 or Claim 10, or a physiologically tolerable salt thereof as active substance, in admixture or conjunction with a pharmaceutically suitable carrier.

12. A pharmaceutical preparation as claimed in Claim 11, which also comprises one or more further active substances.

13. Compounds of formula IV

wherein Rl, R2 and R3 are as defined in Claim 1, and R4 is as defined in Claim 8.

14. Compounds of formula VI

wherein Rl and R2 are as defined in Claim 1.

15. Compounds of formula VII

wherein Rl, R2 and R3 are as defined in Claim 1 and R4 is as defined in Claim 8.

16. Compounds of formula XII

wherein Rl and R2 are as defined in Claim 1.

17. Compounds of formula XVI

wherein R1 and R3 are as defined in Claim 1 R4 is as defined in Claim 8.

18. Compounds of formula XIX

wherein R1 and R3 'are as defined in Claim 1.