Candida tenuis Xylose Reductase Catalyzed Reduction of Aryl Ketones for Enantioselective Synthesis of Active Oxetine Derivatives

Abstract

Candida tenuis xylose reductase shows high catalytic efficiencies in carbonyl reduction of acetophenone and 1-phenyl-1-propanone derivatives. The quite low substrate solubility in aqueous buffer systems is circumvented by addition of methanol or by two-phase solvent systems. In the latter, methanol improves the substrate phase transfer as solvent mediator and leads to reasonable space/time yields. Resulting enantiomerically pure chiral alcohols are key intermediates for synthesis of active pharmaceutical ingredients. (R)-Atomoxetine is exemplarily synthesized in four steps, and the further use for generation of other oxetine derivatives and a polo-like kinase 1 inhibitor are discussed.