Deracemization through Concurrent Oxidation and Reduction

Key words

secondary alcohols - deracemization - domino reaction - oxidation

Significance

Biocatalytic deracemization of sec-alcohols rac-1 has been achieved through a concurrent stereoselective oxidation-reduction sequence affording the S-enantiomer S-1 in highly enantioenriched form (up to er > 99.5:0.5). The authors have identified resting cells of Alcaligenes faecalis DSM 13975 as a highly active and R-enantioselective catalyst for the oxidation of sec-alcohols. Molecular oxygen serves as oxidant. In the reduction step, an S-selective alcohol dehydrogenase, either ADH-‘A’ or RE-ADH, in combination with a cofactor recycling system (glucose/ GDH) was effective. The method has also been applied to the stereoinversion of an enantiopure sec-alcohol. A related system gives access to the R-enantiomer through S-enantioselective oxidation and R-stereoselective reduction.

Comment

Dynamic kinetic resolution of sec-alcohols through the racemization of the alcohol moiety in combination with an (enzymatic) kinetic resolution is a well-established strategy. For the deracemization of alcohols through enantio­selective oxidation and simultaneous stereo­selective reduction of the corresponding ketones no general protocol has been described due to the lack of an applicable sec-alcohol oxidase. In the present work, two examples highlight the use of 2-propanol as an alternative cofactor recycling system resulting in only slightly reduced enantioselectivities. Both enantiomeric forms of the sec-alcohol are accessible. The R-enantiomer, however, is obtained with generally lower enantioselectivities.