Chair of Industrial Organic Chemistry and Biotechnology, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany.
Inorganic and Structural Chemistry, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany.
J Org Chem. 2022 Sep 2;87(17):11369-11378. doi: 10.1021/acs.joc.2c00839. Epub 2022 Aug 15.
In this work, an enantioselective biocatalytic synthesis of chiral thiomorpholines using imine reductases (IREDs) is described. As substrates, four prochiral and one chiral 3,6-dihydro-2-1,4-thiazines were synthesized in a modified Asinger reaction and subsequently reduced using imine reductases as a biocatalyst, NADPH as a cofactor, and a glucose dehydrogenase (GDH)-glucose cofactor regeneration system. As a result, chiral thiomorpholines with a stereogenic center created in 3-position were obtained under mild process conditions with high conversions and excellent enantioselectivities of up to 99%. Furthermore, as a proof of concept, a sequential one-pot process combining both individual reaction steps was achieved.
在这项工作中，描述了使用亚胺还原酶（IREDs）对手性硫代吗啉进行对映选择性生物催化合成。作为底物，通过改良的 Asinger 反应合成了四个前手性和一个手性 3,6-二氢-2-1,4-噻嗪，并随后使用亚胺还原酶作为生物催化剂、NADPH 作为辅因子和葡萄糖脱氢酶（GDH）-葡萄糖辅因子再生系统进行还原。结果，在手性温和的条件下，通过高转化率和高达 99%的优异对映选择性，获得了在 3-位具有手性中心的手性硫代吗啉。此外，作为概念验证，实现了结合两个单独反应步骤的连续一锅法工艺。
