Corrado_2021_Chembiochem__

We present a one-pot multi-enzyme cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5%) and yields (up to 95%) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an omega-transaminase (omegaTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and omegaTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-beta-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5%). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.