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A novel lipase from Aspergillus oryzae WZ007 catalyzed synthesis of brivaracetam intermediate and its enzymatic characterization
Chirality ( IF 2 ) Pub Date : 2020-12-03 , DOI: 10.1002/chir.23286
Qi Li 1 , Mengjie Zhang 1 , Xiaojun Li 2 , Yinjun Zhang 1 , Zhao Wang 1 , Jianyong Zheng 1
Affiliation  

Brivaracetam is a structural derivative of the chiral drug levetiracetam and has been approved for the adjuvant treatment of partial epilepsy. As a new antiepileptic drug, it is widely used in a variety of epilepsy models. In this study, a novel lipase M16 derived from Aspergillus oryzae WZ007 was cloned, expressed, and used for chiral resolution. Lipase M16 has a high enantioselectivity to the racemic substrate (R,S)‐methyl 2‐propylsuccinate 4‐tert‐butyl ester, and the intermediate (R)‐2‐propylsuccinic acid 4‐tert‐butyl ester of brivaracetam was obtained efficiently. Under optimal conditions, the enantiomeric excess of substrate was up to 99.26%, and the e.e.p was 96.23%. The conversion and apparent E value were 50.63% and 342.48, respectively. This study suggests a new biocatalytic resolution via lipase M16 for preparing the brivaracetam chiral intermediate and its potential application in the pharmaceutical industry.

中文翻译:

一种来自米曲霉 WZ007 的新型脂肪酶催化布瓦西坦中间体的合成及其酶学表征

布立西坦是手性药物左乙拉西坦的结构衍生物,已被批准用于部分性癫痫的辅助治疗。作为一种新型抗癫痫药物,广泛应用于多种癫痫模型。在本研究中,一种源自米曲霉WZ007的新型脂肪酶 M16被克隆、表达并用于手性拆分。脂肪酶 M16 对外消旋底物 ( R , S )-2-丙基琥珀酸甲酯4-丁酯具有较高的对映选择性,高效地获得了中间体 ( R )-2-丙基琥珀酸 4-丁酯布利瓦西坦。在最佳条件下,底物对映体过量可达99.26%,ee. p为96.23%。转化率和表观E值分别为 50.63% 和 342.48。该研究提出了一种通过脂肪酶 M16 制备布瓦西坦手性中间体的新生物催化拆分方法及其在制药工业中的潜在应用。
更新日期:2021-01-20
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