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WO1992018477A1 - Azabicycloheptanone - Google Patents

Azabicycloheptanone Download PDF

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Publication number
WO1992018477A1
WO1992018477A1 PCT/GB1992/000731 GB9200731W WO9218477A1 WO 1992018477 A1 WO1992018477 A1 WO 1992018477A1 GB 9200731 W GB9200731 W GB 9200731W WO 9218477 A1 WO9218477 A1 WO 9218477A1
Authority
WO
WIPO (PCT)
Prior art keywords
lactam
iia
iib
enantiomers
pentacin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB1992/000731
Other languages
English (en)
Inventor
Christopher Thomas Evans
Stanley Michael Roberts
Alan Gordon Sutherland
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chiros Ltd
Original Assignee
Chiros Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chiros Ltd filed Critical Chiros Ltd
Publication of WO1992018477A1 publication Critical patent/WO1992018477A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C229/48—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups and carboxyl groups bound to carbon atoms of the same non-condensed ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/12—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/04—Alpha- or beta- amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/006—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures

Definitions

  • This invention relates to bicycloheptanes, their preparation, and their use as chiral synthons.
  • This compound can be prepared by hydrolysis of the ß-lactam (IIa) which may in turn be made by catalytic hydrogenation of the unsaturated ß-lactam (Ia).
  • EP-A-0424064 describes the enantioselective hydrolysis of the ⁇ -lactam 2-azabicyclo[2.2.1]hept-5-en-3-one, utilising enzymatic activity available in deposits NCIMB 40213 and 40249. See also Taylor et al, J. Chem. Soc. Chem. Comm. (1990) 1120. As described by Evans et al, J. Chem. Soc. Perkin Trans. I (1991) 656, the cells used for that ⁇ -lactam are apparently intolerant of structural variation.
  • This invention concerns the enantiomers of azabicycloheptane derivatives of formulae Ia, Ib, IIa and lib which, in optically pure form, are novel compounds.
  • novel compounds are useful as intermediates to optically-pure biologically-active compounds; in particular, preparation of cis-pentacin from an opticallypure ß-lactam precursor (Ia) or (IIa) is advantageous.
  • Suitable activities for the enantioselective transformation are described in EP-A-0424064, e.g. those present in certain novel wild-type isolates of the genera Pseudomonas, Alcalicrenes, Arthrobacter, Brevibacterium, Nocardia, Rhodococcus and Corynebacterium, whilst not being limited to isolates of these genera. Selection for these activities may be conducted in the presence of compounds containing one or more N-acyl substituents. If necessary, elevated levels of activity may be produced by growth of cells in the presence of such compounds. Particular examples of suitable activity are those produced maximally active in cells of the unique strains ENZA-20 and Rhodococcus sp. ENZA-1, the latter when cultivated in a suitable medium in the presence of N-acetyl-L-phenylalanine or N-acetyl-D,L-phenylalanine.
  • Rhodococcus sp. ENZA-1 was isolated from soil samples by enrichment culture in mineral salts medium containing N-acetyl-L-phenylalanine as the sole source of carbon and energy. The isolate has been deposited at the NCIMB in Aberdeen, on 17.10.89. The accession number is NCIMB 40213.
  • the racemic unsaturated ß-lactam (Ia + Ib) is made by the known method of [2+2]cycloaddition of chlorosulphonyl isocyanate onto cyclopentadiene, followed by hydrolytic removal of the chlorosulphonyl function with sodium sulphate. This synthesis is described by Malpass et al, J. Chem. Soc. Perkins Trans. I (1977) 874. For the preparation of cis-pentacin it can be advantageous to proceed via the racemic saturated ß-lactam (IIa + IIb), for this can be made in an efficient cycloaddition between cyclopentene and chlorosulphonyl isocyanate.
  • the enantiomers of formulae Ib and IIb are useful synthons in the preparation of ß-lactams, cis-pentacin analogues and amino-acid isosteres.
  • the compounds of the invention may be substituted, if desired, by non-interfering substituents, i.e. substituents that do not affect the biotransformation.
  • substituents if present are methyl, ethyl, n-butyl, OH, Cl, Br, F, CF 3 and N 3 .
  • the total number of C atoms in the substituent(s) will not usually exceed 8 or, more usually, 4.
  • Rhodococcus equi NCIB 40213 (ENZA-1; 700 mg paste) was suspended in phosphate buffer (0.05 M; pH 7) and racemic 6-azabicyclo[3.2.0]hept-3-en-7-one (340 mg, 3.12 mmol) was added. The mixture was stirred at ambient temperature for 142 h after which the cells were removed by centrifugation. The supernatant was extracted with dichloromethane (4 ⁇ 100 ml) and the combined organic layers were dried (MgSO 4 ) and concentrated. The recovered lactam (197 mg) was reincubated with ENZA-1 (280 mg) in buffer (36 ml) for a further 170 h, then recovered as above.
  • the strain ENZA-1 thus gave, from the racemic ß-lactam (Ia + Ib), the [1R,5S]-(+)-lactam (Ia) in >99% ee and 40% yield together with an amino-acid of opposite configuration which was isolated as its methyl ester, acetamide, in 96% ee.
  • the recovered lactam (Ia) was of the correct stereochemistry for conversion into (-)-cis-pentacin.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

On décrit les énantiomères individuels des composés de β-lactame bicycliques, (Ia), (Ib), (IIa) ou (IIb), éventuellement substitués par un ou des substituents non interférants. Les nouveaux énantiomères s'obtiennent par biotransformation. Les composés (Ia) ou (IIa) sont utilisables dans la synthèse de cis-pentacine chirale.
PCT/GB1992/000731 1991-04-19 1992-04-21 Azabicycloheptanone Ceased WO1992018477A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9108384.0 1991-04-19
GB919108384A GB9108384D0 (en) 1991-04-19 1991-04-19 Bicycloheptanes

Publications (1)

Publication Number Publication Date
WO1992018477A1 true WO1992018477A1 (fr) 1992-10-29

Family

ID=10693565

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1992/000731 Ceased WO1992018477A1 (fr) 1991-04-19 1992-04-21 Azabicycloheptanone

Country Status (3)

Country Link
AU (1) AU1669792A (fr)
GB (1) GB9108384D0 (fr)
WO (1) WO1992018477A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0571870A1 (fr) * 1992-05-29 1993-12-01 Bayer Ag Cyclopentane- et -pentène-bêta-amino-acides
WO1999010519A1 (fr) * 1997-08-22 1999-03-04 Glaxo Group Limited Procede de preparation de lactames n-derivatises a enantiomere enrichi
WO2000058283A1 (fr) * 1999-03-31 2000-10-05 Chirotech Technology Limited Biocatalyseur et son utilisation dans la résolution enzymatique de béta-lactame racémique

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0424064A1 (fr) * 1989-10-16 1991-04-24 Chiroscience Limited Azabicycloheptanones chirales et leur procédé de préparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0424064A1 (fr) * 1989-10-16 1991-04-24 Chiroscience Limited Azabicycloheptanones chirales et leur procédé de préparation

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF THE CHEMICAL SOCIETY PERKIN TRANSACTIONS 1 no. 3, March 1991, pages 656 - 657; C. EVANS ET AL: 'SYNTHESIS OF EITHER ENANTIOMER DF CIS-3-AMINOCYCLOPENTANECARBOXYLIC ACID FROM BOTH ENANTIOMERS OF RACEMIC 2-AZABICYCLO (2.2.1) HEPT-5-EN-3 ONE.' cited in the application *
JOURNAL OF THE CHEMICAL SOCIETY,PERKIN TRANSACTIONS 1 no. 9, September 1991, pages 2276 - 2277; C. EVANS ET AL.: 'WHOLE CELL CATALYSED KINETIC RESOLUTION OF 6-AZABICYCLO(3.2.0)HEP-3-EN-7-ONE: SYNTHESIS OF (-)-CISPENTACIN (FR 109615).' *
TETRAHEDRON LETTERS no. 27, 1972, pages 2793 - 2796; H. REHLING ET AL.: 'CIRCULARDICHROISMUS UND ABSOLUTE KONFIGURATION VON BETA-LACTAMEN' *
THE JOURNAL OF ANTIBIOTICS vol. 42, no. 12, 1989, pages 1749 - 1755; KONISHI ET AL.: 'CISPENTACIN, A NEW ANTIFUNGAL ANTIBIOTIC.' cited in the application *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0571870A1 (fr) * 1992-05-29 1993-12-01 Bayer Ag Cyclopentane- et -pentène-bêta-amino-acides
WO1999010519A1 (fr) * 1997-08-22 1999-03-04 Glaxo Group Limited Procede de preparation de lactames n-derivatises a enantiomere enrichi
US6340587B1 (en) 1997-08-22 2002-01-22 Smithkline Beecham Corporation Process for preparing enantiomerically enriched N-derivatized lactams
AP1104A (en) * 1997-08-22 2002-09-04 Glaxo Group Ltd Process for preparing enantiomerically enriched N-derivatised lactams.
CN1133749C (zh) * 1997-08-22 2004-01-07 葛兰素集团有限公司 对映体富集的n-衍生的内酰胺类化合物的制备方法
WO2000058283A1 (fr) * 1999-03-31 2000-10-05 Chirotech Technology Limited Biocatalyseur et son utilisation dans la résolution enzymatique de béta-lactame racémique

Also Published As

Publication number Publication date
GB9108384D0 (en) 1991-06-05
AU1669792A (en) 1992-11-17

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