Induced axial chirality in biocatalytic asymmetric ketone reduction.
Catalytic asymmetric reduction of prochiral ketones of type 4-alkylidene cyclohexanone with formation of the corresponding axially chiral R-configurated alcohols (up to 99% ee) was achieved using alcohol dehydrogenases, whereas chiral transition-metal catalysts fail. Reversal of enantioselectivity proved to be possible by directed evolution based on saturation mutagenesis (up to 98% ee (S)). Utilization of ketone with a vinyl bromide moiety allows respective R- and S-alcohols to be exploited as key compounds in Pd-catalyzed cascade reactions.
Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein Str., 35032 Marburg, Germany.
Rubén
R
Agudo
Gheorghe-Doru
GD
Roiban
Manfred T
MT
Reetz
D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000438:Alcohols / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D007659:Ketones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D046968:Thermoanaerobacter / Q000201:enzymology
D000438:Alcohols; D007659:Ketones; D000426:Alcohol Dehydrogenase