Ma Ran, Hua Xia, He Cheng-Li, Wang Hui-Hui, Wang Zhu-Xiang, Cui Bao-Dong, Han Wen-Yong, Chen Yong-Zheng, Wan Nan-Wei
Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
Angew Chem Int Ed Engl. 2022 Dec 23;61(52):e202212589. doi: 10.1002/anie.202212589. Epub 2022 Nov 28.
Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy.
扩展用于绿色合成有价值分子的酶工具箱在合成化学和制药工业中仍然备受关注。手性硫杂环丙烷是有价值的含硫杂环化合物，但对映选择性合成它们的相关方法有限。在此，我们报道了一种用于对映选择性合成硫杂环丙烷的生物催化硫代化策略，该策略基于卤代醇脱卤酶（HHDH）催化的环氧化物与硫氰酸盐的对映选择性开环反应以及随后的非酶重排过程而开发。一种新型的HHDH被鉴定并进行了工程改造，用于在制备规模上对各种芳基和烷基取代的环氧化物进行对映选择性生物催化硫代化，以高达43%的分离产率和98%的对映体过量（ee）得到相应的硫杂环丙烷。还进行了手性硫杂环丙烷的大规模合成和有用转化，以证明生物催化硫代化策略的实用性和可扩展性。
