title: 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.
authors: Department of Organic Chemistry, University of Vienna, Wien, Austria.
authors: Michael
authors: M
authors: Vogl
authors: Regina
authors: R
authors: Kratzer
authors: Bernd
authors: B
authors: Nidetzky
authors: Lothar
authors: L
authors: Brecker
mesh_terms: D000098:Acetophenones / Q000737:chemistry; D000449:Aldehyde Reductase / Q000737:chemistry / Q000378:metabolism*; D000069445:Atomoxetine Hydrochloride; D002175:Candida / Q000201:enzymology*; D005473:Fluoxetine / Q000138:chemical synthesis / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011437:Propylamines / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D000098:Acetophenones; D011437:Propylamines; D005473:Fluoxetine; D014867:Water; D000069445:Atomoxetine Hydrochloride; D000449:Aldehyde Reductase; D000432:Methanol