在手性胺的全连续流模式下通过酶促动力学拆分。

Chemoenzymatic Dynamic Kinetic Resolution of Amines in Fully Continuous-Flow Mode.

机构信息

Department of Organic Chemistry and Technology , Budapest University of Technology and Economics , Műegyetem rkp. 3 , H-1111 Budapest , Hungary.

Gedeon Richter Plc. , P.O. Box 27 , H-1475 Budapest , Hungary.

出版信息

Org Lett. 2018 Dec 21;20(24):8052-8056. doi: 10.1021/acs.orglett.8b03676. Epub 2018 Dec 13.

DOI:10.1021/acs.orglett.8b03676

PMID:30543299

Abstract

In this study, lipase-mediated dynamic kinetic resolution (DKR) of various benzylic amines (1a-g) is presented which is realized in a so far unprecedented fully continuous-flow system. The DKR process applying sol-gel immobilized lipase B from Candida antarctica as biocatalyst, palladium on 3-aminopropyl-functionalized silica as racemization catalyst, isopropyl 2-ethoxyacetate as acylating agent, ammonium formate as hydrogen and nitrogen sources, and 2-methyl-2-butanol as solvent under regulated pressure provided the desired products in moderate to good yields with excellent enantiomeric excesses.

摘要

在这项研究中，我们展示了脂肪酶介导的各种苄胺（1a-g）的动态动力学拆分（DKR），这是在迄今为止前所未有的全连续流动系统中实现的。该 DKR 过程采用固定化南极假丝酵母脂肪酶 B 作为生物催化剂、3-氨丙基功能化硅胶负载的钯作为消旋化催化剂、异丙基 2-乙氧基乙酸酯作为酰化剂、甲酸铵作为氢和氮源，以及 2-甲基-2-丁醇作为溶剂，在调节压力下提供了所需产物，产率中等至良好，对映体过量优异。