Stereodivergent Synthesis of Epoxides and Oxazolidinones via theHalohydrin Dehalogenase-Catalyzed Desymmetrization Strategy

Catalytic stereoselective desymmetrization of prochiral com-pounds to valuable chiral molecules is of interest in asymmetric synthesis. Here,we report the development of an efficient biocatalytic desymmetrizationstrategy for the stereodivergent synthesis of various chiral epoxides andoxazolidinones by the identification and engineering of halohydrindehalogenases. The use of stereocomplementary halohydrin dehalogenasesfor the desymmetrization of 2-substituted-1,3-dichloro-2-propanols generateschiral epoxides in up to 95% yield and 99%eeby a single-step dehalogenationreaction, as well as chiral oxazolidinones in up to 88% yield and >99%eevia adehalogenation and cyanate-mediated epoxide ring-opening cascade reaction.We also propose a probable mechanism for stereoselectivity control in thehalohydrin dehalogenase-catalyzed desymmetrization reaction.