Biocatalytic approaches for the synthesis of optically pure vic-halohydrins

Enantiopure vicinal halohydrins (vic-halohydrins) are highly valuable building blocks for the synthesis of many different natural products and pharmaceuticals, and biocatalytic methods for their synthesis have received considerable interest. This review emphasizes the application of biocatalytic approaches as an efficient alternative or complement to conventional chemical reactions, with a special focus on the asymmetric reductions catalyzed by ketoreductases, kinetic resolution catalyzed using lipases or esterases, stereoselective biotransformation catalyzed by halohydrin dehalogenases, asymmetric hydroxylation catalyzed by cytochrome P450 monooxygenases, asymmetric dehalogenation catalyzed by haloalkane dehalogenases, and aldehyde condensation catalyzed by aldolases. Although many chiral vic-halohydrins have been successfully synthesized using wild-type biocatalysts, their enantioselectivity is often too low for enantiopure synthesis. To overcome these limitations, catalytic properties of wild-type enzymes have been improved by rational and semi-rational protein design or directed evolution. This review briefly introduces the research status in this field, highlighting aspects of basic academic research in the biocatalytic synthesis of optically active vic-halohydrins by employing such unconventional approaches. KEY POINTS: • Outlines the enzymatic strategies for the production of enantiopure vic-halohydrins • Highlights recent advances in biocatalytic production of enantiopure vic-halohydrins • Provide guidance for efficient preparation of enantiopure vic-halohydrins.