Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides

Abstract

Micro-organisms were screened for their ability to produce (R)-3-(4-chlorophenyl) glutaric acid monoamide (CGM) from 3-(4-chlorophenyl) glutaric acid diamide (CGD) through stereoselective hydrolysis. (R)-CGM is a useful synthetic intermediate for arbaclofen. Four CGD-assimilating micro-organisms were found to be potential catalysts for (R)-CGM production. Among these micro-organisms, Comamonas sp. KNK3-7 (NITE BP-963) produced (R)-CGM with the highest optical purity [98.7% enantiomeric excess (e.e.)] and was selected as the most promising strain. In addition, Comamonas sp. KNK3-7 could asymmetrically hydrolyse 3-isobutyl glutaric acid diamide (IBD) to produce (R)-3-isobutyl glutaric acid monoamide [(R)-IBM] with high optical purity (>99.0% e.e.). The synthesis of a (R)-3-substituted glutaric acid monoamide by desymmetrization of 3-substituted glutaric acid diamide with a micro-organism and an enzyme has not been previously reported. This finding indicates the possibility of the preparation of a variety of optically active 3-substituted glutaric acid monoamides using the amidase from Comamonas sp. KNK3-7. The amidase from Comamonas sp. KNK3-7 may be useful for the chemoenzymatic synthesis of various kinds of chiral gamma-aminobutyric acids and may be used in a 'green' process to produce gamma-aminobutyric acids.