Deracemization By Simultaneous Bio-oxidative Kinetic Resolution and Stereoinversion

Deracemization, that is, the transformation of a racemate into a single product enantiomer with theoretically 100 % conversion and 100 % ee, is an appealing but also challenging option for asymmetric synthesis. Herein a novel chemo‐enzymatic deracemization concept by a cascade is described: the pathway involves two enantioselective oxidation steps and one non‐stereoselective reduction step, enabling stereoinversion and a simultaneous kinetic resolution. The concept was exemplified for the transformation of rac‐benzylisoquinolines to optically pure (S)‐berbines. The racemic substrates were transformed to optically pure products (ee>97 %) with up to 98 % conversion and up to 88 % yield of isolated product. From two make one: Chemo‐enzymatic stereoinversion and enzymatic kinetic resolution have been combined in a simultaneous cascade process to transform racemic substrates (A, ent‐A) into optically pure product P. The concept was exemplified for benzylisoquinolines rac‐1 yielding optically pure berbines (S)‐2. The reaction system comprised a monoamine oxidase (MAO‐N), morpholine‐borane, and the berberine bridge enzyme (BBE).