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

Abstract

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

Inhibitory Effect of DMSO on Halohydrin Dehalogenase: Experimental and Computational Insights into the Influence of an Organic Co‐solvent on the Structural and Catalytic Properties of a Biocatalyst

“…The ability of halohydrin dehalogenases (HHDHs) to catalyse epoxide ring-opening reactions in an enantioselective fashion [1][2][3][4] as well as their implementation in enzymatic cascades, [5][6][7][8][9][10][11][12][13][14] have been intensively explored over the years primarily due to the synthetic value of the products. [11,[15][16][17] Because of the poor solubility of substrates, biocatalytic reactions are usually performed with the addition of a small amount of organic solvent (OS).…”