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研究报告

酰胺酶拆分制备左乙拉西坦手性中间体 (S)-2-氨基丁酰胺的初步研究

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  • 浙江工业大学生物工程研究所,浙江杭州310014
郑仁朝(1980—),男,浙江奉化人,教授,博士,研究方向为手性生物催化,E-mail:zhengrc@zjut.edu.cn. 通信作者:郑裕国教授,E-mail:zhengyg@zjut.edu.cn.

基金资助

国家高技术研究发展计划(863 计划)(2012AA022201B)

Amidase-catalyzed enantioselective synthesis of chiral intermediate of levetiracetam (S)-2-aminobutyramide

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  • Institute of Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China

摘要

(S)-2-氨基丁酰胺是癫痫治疗药物左乙拉西坦的关键手性中间体。筛选获得了能够立体选择性拆分2-氨基丁酰胺合成(S)-2-氨基丁酰胺的重组酰胺酶Dt-Ami 6。考察了温度、pH、有机共溶剂及不同底物浓度对催化反应的影响。结果表明,该酶的最适催化温度为40 ℃,最适底物浓度为1 mol/L,湿菌体最适添加量为8 g/L,在去离子水中反应40 min,(S)-2-氨基丁酰胺的收率为41.7%,光学纯度达94.0%。

本文引用格式

郑仁朝,佘勇,郑裕国 . 酰胺酶拆分制备左乙拉西坦手性中间体 (S)-2-氨基丁酰胺的初步研究[J]. 发酵科技通讯, 2015 , 44(3) : 1 -5 . DOI: 10.16774/j.cnki.issn.1674-2214.2015.03.004

Abstract

(S)-2-aminobutyramide is the key chiral intermediate of levetiracetam, an important drug for the treatment of epilepsy. A recombinant amidase Dt-Ami 6 was screened as the best biocatalyst for enantioselective synthesis of (S) -2 -aminobutyramide. The reaction parameters including temperature, pH, organic cosolvent and substrate concentrations were investigated. The results indicated that the optimum temperature, substrate concentration, biocatalyst loading and reaction time were 40 ℃, 1 mol/L, 8 g/L and 40 min, respectively. Under these conditions, (S)-2- aminobutyramide was obtained in 41.7% yield and 94.0% e.e..
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