Wu Jing-Fei, Wan Nan-Wei, Li Ying-Na, Wang Qing-Ping, Cui Bao-Dong, Han Wen-Yong, Chen Yong-Zheng
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, 563000, 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, 563000, China.
iScience. 2021 Jul 17;24(8):102883. doi: 10.1016/j.isci.2021.102883. eCollection 2021 Aug 20.
Asymmetric functionalization of alkenes allows the direct synthesis of a wide range of chiral compounds. Vicinal hydroxyazidation of alkenes provides a desirable path to 1,2-azidoalcohols; however, existing methods are limited by the control of stereoselectivity and regioselectivity. Herein, we describe a dual-enzyme cascade strategy for regiodivergent and stereoselective hydroxyazidation of alkenes, affording various enantiomerically pure 1,2-azidoalcohols. The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regioselective ring opening of epoxides with azide. Additionally, a one-pot chemo-enzymatic route to chiral -hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.
烯烃的不对称官能团化能够直接合成多种手性化合物。烯烃的邻位羟基叠氮化反应为制备1,2-叠氮醇提供了一条理想途径；然而，现有方法在立体选择性和区域选择性控制方面存在局限性。在此，我们描述了一种双酶级联策略，用于烯烃的区域发散性和立体选择性羟基叠氮化反应，可提供各种对映体纯的1,2-叠氮醇。该生物催化级联过程是通过将苯乙烯单加氧酶催化的烯烃不对称环氧化反应与卤代醇脱卤酶催化的环氧化物与叠氮化物的区域选择性开环反应相结合而设计的。此外，通过将生物催化级联反应与铜催化的叠氮化物-炔烃环加成反应相结合，开发了一种从烯烃制备手性β-羟基三唑的一锅法化学酶促路线。
