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US5284769A Expired / Lapsed US ⏱️ 0.0 years remaining

Process for preparing a single enantiomer of a lactam using lactamase

Assignee: Chirotech Technology Ltd
•
Filing: 1993-05-20
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Granted: 1994-02-08
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Expires: 2013-05-20
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Abstract

Abstract Lactams of 1-amino-3-carboxylic acid cyclic compounds are produced in enantiomeric form, together with an enantiomer of the corresponding ring-opened amino-acid or ester, by reaction of the racemic lactam with a novel lactamase. The products are useful in the synthesis of chiral carbocyclic nucleotides.

Inventors

  • 👤 Christopher T. Evans
  • 👤 Stanley M. Roberts

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-26 17:00
CPC Classifications
C; C12; C12P; C12P13/00; C12P13/001; C07; C07D; C07D209/00; C07D209/02; C07D209/52; C12P13/02; C12P17/00; C12P17/10; C12P41/00; C12P41/006

Claims Analysis

Total Claims: 21
Claim 1
Independent Claim 216 words
A process for preparing a single enantiomer, substantially free of other enantiomers, of a lactam of the formula ##STR5## wherein X is --CH 2 --, --(CH 2 ) 2 --, --CH 2 --Q-- --Q--CH 2 - and Q is a heteroatom (including NH); either Y and Z are independently selected from --CH 2 -- and a heteroatom (including NH) or --Y--Z-- is --CH═CH--, --CH═CH--, --CH═CH--; and R n is absent or represents one or more independently-selected substituents which do not interfere with the lacatamase reaction at any available position(s) on the X,Y,Z-containing ring; said process comprising the steps of: (a) reacting a mixture of enantiomers of the lactam of formula I with either (1) [an enzyme having lactamase activity] a lactamase capable of stereoselective cleavage of one of said enantiomers, or (2) a microorganism [having said lactamase activity] which produces said lactamase, thereby forming a mixture of said single enantiomer of the lactam of formula I and an enantiomer, having the opposite stereochemical configuration, of the formula ##STR6## wherein X, Y, Z and R n are as defined above; R 1 is H or alkyl; and R 2 is H or a N-blocking group; (b) isolating said single enantiomer of said lactam of formula I, and optionally isolating said enantiomer of opposite configuration of formula II.
Claim 2
Dependent Claim 216 words
A process for preparing a single enantiomer, substantially free of other enantiomers, of a lactam of the formula ##STR5## wherein X is --CH 2 --, --(CH 2 ) 2 --, --CH 2 --Q-- --Q--CH 2 - and Q is a heteroatom (including NH); either Y and Z are independently selected from --CH 2 -- and a heteroatom (including NH) or --Y--Z-- is --CH═CH--, --CH═CH--, --CH═CH--; and R n is absent or represents one or more independently-selected substituents which do not interfere with the lacatamase reaction at any available position(s) on the X,Y,Z-containing ring; said process comprising the steps of: (a) reacting a mixture of enantiomers of the lactam of formula I with either (1) [an enzyme having lactamase activity] a lactamase capable of stereoselective cleavage of one of said enantiomers, or (2) a microorganism [having said lactamase activity] which produces said lactamase, thereby forming a mixture of said single enantiomer of the lactam of formula I and an enantiomer, having the opposite stereochemical configuration, of the formula ##STR6## wherein X, Y, Z and R n are as defined above; R 1 is H or alkyl; and R 2 is H or a N-blocking group; (b) isolating said single enantiomer of said lactam of formula I, and optionally isolating said enantiomer of opposite configuration of formula II.
Claim 3
Dependent Claim 10 words
The process of claim 1, wherein R 1 is methyl.
Claim 4
Dependent Claim 10 words
The process of claim 1, wherein R 1 is H.
Claim 5
Dependent Claim 11 words
The process of claim 1, wherein R 2 , is acetyl.
Claim 6
Dependent Claim 10 words
The process of claim 1, wherein R 2 is H.
Claim 7
Dependent Claim 10 words
The process of claim 1, wherein R n is absent.
Claim 8
Dependent Claim 11 words
The process of claim 1, wherein X is --CH 2 --.
Claim 9
Dependent Claim 9 words
The process of claim 1, wherein --Y--Z-- is --CH═CH--.
Claim 10
Dependent Claim 14 words
The process of claim 1, wherein said enantiomer of formula II is (-)-4-aminiocyclopent-2-ene-1-carboxylic acid.
Claim 11
Dependent Claim 20 words
The process of claim 1, wherein said mixture of enantiomers of said lactam of formula I is a racemic mixture.
Claim 12
Dependent Claim 15 words
The process of claim 1, wherein said enantiomer of formula I is 2-2- azabicyclo[2.2.1] hept-5-en-3-one.
Claim 13
Dependent Claim 14 words
The process of claim 1 wherein said enzyme (1) is used in step (a).
Claim 14
Dependent Claim 32 words
The process of claim 12, wherein said enzyme is characterized by the ability to cause stereoselective formation of an enantiomer of 2-azabicyclo[2.2.1]hept-5-en-3-one and (-) or (+)-4-aminocyclo-pent-2-ene-1 carboxylic acid from racemic 2-azabicyclo-[2.2.1]hept -5-en-3-one.
Claim 15
Dependent Claim 14 words
The process of claim 1, wherein said microorganism (2) is used in step (a).
Claim 16
Dependent Claim 23 words
The process of claim 12, wherein said enzyme is present as a component of a cell-free extract of a microorganism having lactamase activity.
Claim 17
Dependent Claim 24 words
The process of claim 15, wherein said microorganism has the characteristics of that deposited as NCIMB 40123 or NCIMB 40249, or a mutant thereof.
Claim 18
Dependent Claim 30 words
The process of claim 1, wherein in step (b), said lactam is reacted in the presence of a nucleophile, whereby the amino ester (R 1 is not H) is formed.
Claim 19
Dependent Claim 30 words
The process of claim 11, wherein R n is selected from the group consisting of methyl, ethyl, n-butyl, OH, Cl, Br, F, CF 3 , PhCH 2 O and azido.
Claim 20
Dependent Claim 11 words
The process of claim 18, wherein n is 1 or 2.
Claim 21
Dependent Claim 19 words
The process of claim 18 wherein the total number of carbon atoms in R n does not exceed 8.

References Cited (Backward Citations)

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3.5 Years (Year 4) 1997-02-07 1997-08-09 1998-02-08 $2000.00 Window Closed / Lapsed
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