Biocatalytic Cascade for the Synthesis of Enantiopure β-Azidoalcohols and β-Hydroxynitriles

A three-step, two-enzyme, one-pot reaction sequence starting from prochiral alpha-chloroketones leading to enantiopure beta-azidoalcohols and beta-hydroxynitriles is described. Asymmetric bioreduction of alpha-chloroketones by hydrogen transfer catalysed by an alcohol dehydrogenase (ADH) established the stereogenic centre in the first step to furnish enantiopure chlorohydrin intermediates. Subsequent biocatalysed ring closure to the epoxide and nucleophilic ring opening with azide, N-3(-), or cyanide, CN-, both catalysed by a nonselective halohydrin dehalogenase (Hhe) proceeded with full retention of configuration to give enantiopure beta-azidoalcohols and beta-hydroxynitriles, respectively. Both enantiomers of various optically pure beta-azidoalcohols and beta-hydroxynitriles were synthesised. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)