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  

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

作　　者：郑仁朝[1] 佘勇[1] 郑裕国[1] 

机构地区：[1]浙江工业大学生物工程研究所,浙江杭州310014

出　　处：《发酵科技通讯》2015年第3期1-5,共5页Bulletin of Fermentation Science and Technology

基　　金：国家高技术研究发展计划(863计划)(2012AA022201B)

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、p H、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%。（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..

关 键 词：酰胺酶 立体选择性水解 (S)-2-氨基丁酰胺 左乙拉西坦 

分 类 号：TQ46[化学工程—制药化工]