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The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase
Chirality ( IF 2.8 ) Pub Date : 2022-06-17 , DOI: 10.1002/chir.23482
Yuele Lu 1 , Rong Zhan 1 , Beibei Song 1 , Yaoyao Zhou 1 , Linjiang Zhu 1 , Hanchi Chen 1 , Xiaolong Chen 1
Affiliation  

Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.s) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam.

中文翻译:

不动杆菌优化生物催化合成(S)-2-氯丁酸甲酯。脂肪酶

癫痫是一种由脑神经元突然异常放电引起的慢性疾病,导致短暂的脑功能障碍。比利时UCB公司研制的左乙拉西坦是治疗癫痫的有效药物。( S )-2-氯丁酸甲酯是左乙拉西坦的重要手性结构单元,引起了广泛关注。在这项研究中,一株脂肪酶产生的不动杆菌属。zjutfet-1 是从土壤样品中筛选出来的。在优化的发酵和生物催化条件下,细菌脂肪酶表现出高的水解催化活性和对消旋2-氯丁酸甲酯的立体选择性。当酶促反应在 6% 的外消旋底物中进行时,对映体过量 ( e .e . s ) 达到95%以上,收率86%以上。因此,该脂肪酶可高效分解外消旋的2-氯丁酸甲酯,得到( S )-2-氯丁酸甲酯,在左乙拉西坦的工业化生产中具有很大的应用潜力。
更新日期:2022-06-17
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