title: Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides.
abstract: OBJECTIVE
  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.
  
  
  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.).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Frontier Biochemical & Medicinal Research Laboratories, Kaneka Corporation, Takasago, Hyogo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nojiri
authors.forename: K
authors.initials: K
authors.lastname: Uekita
authors.forename: M
authors.initials: M
authors.lastname: Ohnuki
authors.forename: N
authors.initials: N
authors.lastname: Taoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yasohara
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D002384:Catalysis; D020585:Comamonas / Q000378:metabolism*; D003958:Diamide / Q000737:chemistry*; D005977:Glutarates / Q000737:chemistry*; D006868:Hydrolysis; D013237:Stereoisomerism
chemical_list: C587812:(R)-3-(4-chlorophenyl) glutaric acid monoamide; C587813:3-(4-chlorophenyl) glutaric acid diamide; D005977:Glutarates; D003958:Diamide; D000581:Amidohydrolases; C019665:amidase
keywords: Comamonas sp; amidase; arbaclofen; desymmetrization; glutaric acid diamide derivatives; pregabalin