Synthesis of Chiral Sulfoxides by A Cyclic Oxidation‐Reduction Multi‐Enzymatic Cascade Biocatalysis

Optically pure sulfoxides are valuable organosulfur compounds extensively employed in medicinal and organic synthesis. In this study, we present a biocatalytic oxidation‐reduction cascade system designed for the preparation of enantiopure sulfoxides. The system involves the cooperation of a low‐enantioselective chimeric oxidase SMO (styrene monooxygenase) with a high‐enantioselective reductase MsrA (methionine sulfoxide reductase A), facilitating “non‐selective oxidation and selective reduction” cycles for prochiral sulfide oxidation. The regeneration of requisite cofactors for MsrA and SMO was achieved via a cascade catalysis process involving three auxiliary enzymes, sustained by cost‐effective D‐glucose. Under the optimal reaction conditions, a series of heteroaryl alkyl, aryl alkyl and dialkyl sulfoxides in R configuration were synthesized through this “one‐pot, one step” cascade reaction. The obtained compounds exhibited high yields of >90 % and demonstrated enantiomeric excess (ee) values exceeding 90 %. This study represents an unconventional and efficient biocatalytic way in utilizing the low‐enantioselective oxidase for the synthesis of enantiopure sulfoxides. An unconventional biocatalytic oxidation‐reduction cascade system with cofactor regeneration was established for the synthesis of enantiopure sulfoxides using prochiral sulfildes as substrates. Heteroaryl alkyl, aryl alkyl and dialkyl sulfoxides in R configuration were prepared in >90 % conversion with >90 % ee through the cascade catalysis of MsrA, Fus‐SMO and three other auxiliary enzymes (Trx, Trx‐R, and GDH).