LIPASE-CATALYZED ASYMMETRIC HYDROLYSIS OF 3-PHENYLGLYCIDIC ACID ESTER, THE KEY INTERMEDIATE IN THE SYNTHESIS OF DILTIAZEM HYDROCHLORIDE

被引:85
作者
MATSUMAE, H
FURUI, M
SHIBATANI, T
机构
[1] Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Yodogawa-ku, Osaka, 532, 16-89
来源
JOURNAL OF FERMENTATION AND BIOENGINEERING | 1993年 / 75卷 / 02期
关键词
D O I
10.1016/0922-338X(93)90216-U
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Asymmetric hydrolytic enzymes for tans-3-(4-methoxyphenyl)glycidic acid methyl ester [(+/-)-MPGM], a key intermediate in the synthesis of di ti zem hydrochloride that is useful as a coronary vasodilator, were screened from 730 microorganisms. Among the microbial enzymes tested, Serratia marcescens lipase had the highest enantioselectivity (E = 135) for hydrolysis of (+/-)-MPGM in a two-phase system using water (pH 8) and a water-immiscible solvent such as toluene. Resolution of (+/-)-MPGM by S. marcescens lipase gave (2R, 3S)-3-(4-methoxyphenyl)glycidic acid methyl ester [(-)-MPGM] with a reaction yield of 48% and optical purity of >99.9% e.e. After the reaction, the emulsion of toluene and water was separated into two clear layers by the addition of sodium dodecyl sulfate. The crystalline (-)-MPGM was isolated with a yield of over 43% and optical purity of 100% e.e. without column treatment. Diltiazem hydrochloride synthesis using asymmetric hydrolysis of (+/-)-MPGM was found to be a more efficient process compared to the conventional chemical synthetic process. Some enzymatic characterizations on asymmetric hydrolysis in two-phases of organic solvent-water by S. marcescens lipase were investigated.
引用
收藏
页码:93 / 98
页数:6
相关论文
共 10 条