猪胰脂肪酶催化外消旋P-手性α-羟基磷酸酯类化合物的动力学拆分  

Kinetic Resolution of Racemic P-Chiralα-Hydroxymethylphosphonates Catalyzed by Lipase from Porcine Pancreas

作　　者：胡慧娟 闫巧丽 卢晓刚 杨启帆 裴承新 王红梅 高润利 Hu Huijuan;Yan Qiaoli;Lu Xiaogang;Yang Qifan;Pei Chengxin;Wang Hongmei;Gao Runli(State Key Laboratory of NBC Protection for Civilian,Beijing 102205)

机构地区：[1]国民核生化灾害防护国家重点实验室,北京102205

出　　处：《有机化学》2023年第8期2815-2825,共11页Chinese Journal of Organic Chemistry

基　　金：国民核生化灾害防护国家重点实验室(No.SKLNBC2021-09)资助项目.

摘　　要：酶催化具有高效、高选择性以及反应条件温和等优点,已经成为有机合成领域的重要方法.研究了P-手性α-羟基磷(膦)酸酯类化合物的合成方法.在猪胰脂肪酶的催化作用下,外消旋α-羟基磷(膦)酸酯与乙酸乙烯酯之间能够顺利地发生酯交换反应,以高达49%的产率和83%的ee值得到相应的手性产物,且该反应在非常温和的条件下就能够进行.同时,在计算机的辅助下建立了酶-底物之间的结合模型,通过对接的方法揭示了反应中酶催化对映选择性的机理.The development of enzyme-catalyzed methods for the synthesis of P-chiral phosphine derivatives has important implications.Herein this work presents a direct biocatalytic transesterification of racemicα-hydroxyphosphonates and vinyl acetate,which provides a rapid access to P-chiral hydroxymethylphosphonates.Catalyzed by lipase from porcine pancreas(PPL),which is commercially available,the reactions proceed efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides in up to 49%yield and 83%ee under very mild conditions.The enzyme-substrate binding mode was established and the high enantioselectivity of PPL was revealed through docking simulations.

关 键 词：生物催化 动力学拆分 羟基磷酸酯 猪胰脂肪酶 

分 类 号：TQ426.97[化学工程] O623.624[理学—有机化学]