Deracemization By Simultaneous Bio-oxidative Kinetic Resolution and Stereoinversion

• Published in: Angewandte Chemie International Edition Vol. 53; no. 14; pp. 3731 - 3734
• Main Authors: Schrittwieser, Joerg H., Groenendaal, Bas, Resch, Verena, Ghislieri, Diego, Wallner, Silvia, Fischereder, Eva-Maria, Fuchs, Elisabeth, Grischek, Barbara, Sattler, Johann H., Macheroux, Peter, Turner, Nicholas J., Kroutil, Wolfgang
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.04.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: alkaloids; Alkaloids - chemistry; asymmetric synthesis; Asymmetry; Bridges (structures); Cascades; Catalysis; Chemistry; Chemistry, Multidisciplinary; Communications; Conversion; CC coupling; deracemization; enzyme catalysis; Kinetics; Molecular Conformation; Oxidase; Oxidation-Reduction; Physical Sciences; Reaction kinetics; Science & Technology; simultaneous cascades; Stereoisomerism; Transformations; Transforms; deracemization; alkaloids; enzyme catalysis; DERACEMISATION; RADICAL-MEDIATED RACEMIZATION; ALKALINE-EARTH SUPPORTS; CHIRAL AMINES; CC coupling; asymmetric synthesis; 1,2-DEHYDRORETICULINE; PD; OXIDASE; BERBERINE BRIDGE ENZYME; PRIMARY AMINES; simultaneous cascades; CATALYSTS; CC coupling
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201400027

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).