Department of Biochemistry, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi City, Guizhou Province, P. R. China.
Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi City, Guizhou Province, P. R. China.
Chemistry. 2024 Apr 2;30(19):e202304081. doi: 10.1002/chem.202304081. Epub 2024 Feb 15.
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.
旋光纯亚砜是一类在药物和有机合成中广泛应用的有价值的有机硫化合物。在本研究中，我们提出了一种设计用于制备对映体纯亚砜的生物催化氧化还原级联系统。该系统涉及低对映选择性嵌合氧化酶 SMO（苯乙烯单加氧酶）与高对映选择性还原酶 MsrA（甲硫氨酸亚砜还原酶 A）的合作，促进了前手性硫醚的“非选择性氧化和选择性还原”循环氧化。通过涉及三种辅助酶的级联催化过程，实现了 MsrA 和 SMO 所需辅因子的再生，该过程由经济高效的 D-葡萄糖维持。在最佳反应条件下，通过“一锅一步”级联反应合成了一系列 R 构型的杂芳基烷基、芳基烷基和二烷基亚砜。获得的化合物的产率>90%，对映过量值（ee）超过 90%。这项研究代表了一种利用低对映选择性氧化酶合成对映体纯亚砜的非常规且高效的生物催化方法。
