Biocatalytic desymmetric hydrolysis of 3-(4-chlorophenyl)-glutaronitrile to the key precursor of optically pure baclofen.
- Author:
Meizhen XU
1
;
Jie REN
;
Jingsong GONG
;
Wenyue DONG
;
Qiaqing WU
;
Zhenghong XU
;
Dunming ZHU
Author Information
1. Laboratory of Pharmaceutical Engineering, School of Medicine and Pharmaceutics, Jiangnan University, Wuxi 214122, Jiangsu, China.
- Publication Type:Journal Article
- MeSH:
Aminohydrolases;
metabolism;
Baclofen;
chemical synthesis;
chemistry;
Biocatalysis;
Chlorophenols;
chemistry;
Gibberella;
enzymology;
Hydrolysis;
Nitriles;
chemistry;
Prodrugs;
chemical synthesis;
chemistry
- From:
Chinese Journal of Biotechnology
2013;29(1):31-40
- CountryChina
- Language:Chinese
-
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.
