Two (Chemo)-Enzymatic Cascades for the Production of Opposite Enantiomers of Chiral Azidoalcohols

Multi-step cascade reactions have gained increasing attention in the biocatalysis field recent years. In particular, multi-enzymatic cascades can achieve high molecular complexity without workup of reaction intermediates thanks to enzymes’ intrinsic selectivity; and where enzymes fall short, organo- or metal catalysts further expand range possible synthetic routes. Here, we present two enantiocomplementary (chemo)-enzymatic composed either a styrene monooxygenase (StyAB) Shi epoxidation catalyst for enantioselective alkene first step, coupled with halohydrin dehalogenase (HHDH)-catalysed regioselective epoxide ring opening second step synthesis chiral aliphatic non-terminal azidoalcohols. Through controlled formation new stereocenters, corresponding azidoalcohol products could be obtained regioselectivity excellent enantioselectivity (99% ee) StyAB-HHDH cascade, while product enantiomeric excesses Shi-HHDH ranged between 56 61%.