Synthesis of enantiopure epoxide by ‘one pot’ chemoenzymatic approach using a highly enantioselective dehydrogenase

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• 作者：Kai Wu ; Lifeng Chen ; Haiyang Fan ; Zhiqiang Zhao ; Hualei Wang ; ^{hlwang@ecust.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Dongzhi Wei ; ^{dzhwei@ecust.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alcohol dehydrogenase ; Enantioselectivity ; Epoxide ; Halohydrin
• 刊名：Tetrahedron Letters
• 出版年：2016
• 出版时间：24 February 2016
• 年：2016
• 卷：57
• 期：8
• 页码：899-904
• 全文大小：572 K

文摘

Enantiopure α-phenethyl alcohols, including aromatic halohydrins, are important chiral building blocks. One of the best approaches to synthesise α-phenethyl alcohols is asymmetric reduction of prochiral ketones by alcohol dehydrogenases (ADHs). The obtained enantiopure halohydrin could be directly used to produce enantiopure epoxide through a base-induced ring-closure reaction, which is an attractive ‘one pot’ chemoenzymatic method for producing high-yield epoxide. In this study, a novel medium-chain dehydrogenase (KcDH) from Kuraishia capsulate CBS1993 was identified and characterised to show its broad substrate scope and excellent enantioselectivity. KcDH showed activities on 25 substrates of the 26 tested aromatic ketones and heteroaryl ketones, with an enantiomeric excess (ee) >99% and the highest relative activity observed with para-nitro acetophenone. Due to its high enantioselectivity for α-haloketones, a chemoenzymatic method for the synthesis of enantiopure styrene oxide (SO) and phenyl glycidyl ether (PGE) was developed through a base-induced ring-closure reaction on enantiopure halohydrin obtained with KcDH. (R)-SO and (S)-PGE were obtained in 86% and 94% analytical yield, respectively, and both epoxides were obtained with ee >99%. Thus, our results suggested that KcDH may be a promising biocatalyst for the production of multiple enantiopure α-phenethyl alcohols and epoxides.