Orchestration of concurrent oxidation and reduction cycles for stereoinversion and deracemisation of sec-alcohols.
Black and white are opposites as are oxidation and reduction. Performing an oxidation, for example, of a sec-alcohol and a reduction of the corresponding ketone in the same vessel without separation of the reagents seems to be an impossible task. Here we show that oxidative cofactor recycling of NADP (+) and reductive regeneration of NADH can be performed simultaneously in the same compartment without significant interference. Regeneration cycles can be run in opposing directions beside each other enabling one-pot transformation of racemic alcohols to one enantiomer via concurrent enantioselective oxidation and asymmetric reduction employing defined alcohol dehydrogenases with opposite stereo- and cofactor-preference. Thus, by careful selection of appropriate enzymes, NADH recycling can be performed in the presence of NADP (+) recycling to achieve overall, for example, deracemisation of sec-alcohols or stereoinversion representing a possible concept for a "green" equivalent to the chemical-intensive Mitsunobu inversion.
Voss
Constance V
CV
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Gruber
Christian C
CC
Faber
Kurt
K
Knaus
Tanja
T
Macheroux
Peter
P
Kroutil
Wolfgang
W
D000426:Alcohol Dehydrogenase / Q000737:chemistry; D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D008968:Molecular Conformation; D009243:NAD / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000438:Alcohols; D007659:Ketones; D009243:NAD; D009249:NADP; D000426:Alcohol Dehydrogenase