title: [Biocatalytic desymmetric hydrolysis of 3-(4-chlorophenyl)-glutaronitrile to the key precursor of optically pure baclofen].
abstract: We produced (S)-4-cyano-3-(4-chlorophenyl)-butyrate by highly stereoselective biocatalyst in this study. A nitrilase-producing strain, named Gibberella intermedia WX12, was isolated by 3-(4-chlorophenyl)-glutaronitrile as substrate in the screening with phenol-sodium hypochlorite method. The fermentation conditions and catalytic properties of this strain were investigated. The preferred carbon and nitrogen sources for nitrilase production were lactose (30 g/L) and peptone (20 g/L). After being cultivated for 96 h, the cells were collected for use in biotransformation. The hydrolysis of 3-(4-chlorophenyl)-glutaronitrile was performed at 30 degrees C in phosphate buffer (pH 8.0, 50 mmol/L) for 24 h to give (S)-4-cyano-3-(4-chlorophenyl)-butyric acid with 90% yield and > 99% of ee, which can be used for the synthesis of (R)- and (S)-baclofen. The configuration of product was determined by chemically converting it to baclofen and comparison with the authentic sample by chiral HPLC analysis.
authors: Laboratory of Pharmaceutical Engineering, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi 214122, Jiangsu, China.
authors: Meizhen
authors: M
authors: Xu
authors: Jie
authors: J
authors: Ren
authors: Jingsong
authors: J
authors: Gong
authors: Wenyue
authors: W
authors: Dong
authors: Qiaqing
authors: Q
authors: Wu
authors: Zhenghong
authors: Z
authors: Xu
authors: Dunming
authors: D
authors: Zhu
mesh_terms: D000619:Aminohydrolases / Q000378:metabolism; D001418:Baclofen / Q000138:chemical synthesis* / Q000737:chemistry; D055162:Biocatalysis; D002733:Chlorophenols / Q000737:chemistry*; D005874:Gibberella / Q000201:enzymology; D006868:Hydrolysis; D009570:Nitriles / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C000592872:3-(4-chlorophenyl)-glutaronitrile; D002733:Chlorophenols; D009570:Nitriles; D011355:Prodrugs; D000619:Aminohydrolases; C021867:nitrilase; D001418:Baclofen