Enantioselective Synthesis of Thiomorpholines through Biocatalytic Reduction of 3,6-Dihydro-2H-1,4-thiazines Using Imine Reductases.

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-2H-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.

Citation

Jannis Nonnhoff, Hans-Georg Stammler, Harald Gröger. Enantioselective Synthesis of Thiomorpholines through Biocatalytic Reduction of 3,6-Dihydro-2H-1,4-thiazines Using Imine Reductases. The Journal of organic chemistry. 2022 Sep 02;87(17):11369-11378

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PMID: 35969670

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