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Microbial asymmetric hydrolysis of 3‐substituted glutaric acid diamides
Author(s) -
Nojiri M.,
Uekita K.,
Ohnuki M.,
Taoka N.,
Yasohara Y.
Publication year - 2013
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.12309
Subject(s) - glutaric acid , desymmetrization , comamonas , chemistry , hydrolysis , organic chemistry , enantiomeric excess , amidase , stereoselectivity , enantiomer , stereochemistry , enantioselective synthesis , catalysis , bacteria , biology , pseudomonas , genetics
Aims 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. Methods and Results Four CGD ‐assimilating micro‐organisms were found to be potential catalysts for ( R )‐ CGM production. Among these micro‐organisms, Comamonas sp. KNK 3‐7 ( 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. KNK 3‐7 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.). Conclusion 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. KNK 3‐7. Significance and Impact of the Study The amidase from Comamonas sp. KNK 3‐7 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.