Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides

Autor: Masutoshi Nojiri, Yoshihiko Yasohara, Masatoshi Ohnuki, Ken Uekita, Naoaki Taoka
Rok vydání: 2013
Předmět:
Zdroj: Journal of Applied Microbiology. 115:1127-1133
ISSN: 1364-5072
DOI: 10.1111/jam.12309
Popis: 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. 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.). 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. KNK3-7. Significance and Impact of the Study 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.
Databáze: OpenAIRE
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