Photo-Biocatalytic One-Pot Cascade Reaction for the Asymmetric Synthesis of Hydroxysulfone Compounds

Asymmetric synthesis of chiral hydroxysulfones, key pharmaceutical intermediates, is challenging. We report an efficient synthesis from readily available materials via a one-pot photo-biocatalytic cascade reaction in aqueous conditions, utilizing visible light as an energy source. This sustainable process achieves up to 84% yields and 99% ee. Engineered ketoreductase produces R-configured products with high conversion and enantioselectivity across diverse substrates. Molecular dynamics (MD) simulations explored enzyme–substrate interactions and their influence on reaction activity and stereoselectivity.