Controlling enantioselectivity of alcohol dehydrogenase-catalyzed transformations using site-directed mutagenesis enabled their use in stereoinversion of enantiomerically pure alcohols. We developed a single-enzymatic approach for stereoinversion of R-configured alcohols to the opposite enantiomer in high percent conversion and high enantioselectivity. A single mutant of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase was used in this approach. Oxidation under conditions that allows selectivity mistakes to take place enabled the depletion of R alcohol to the corresponding ketone, which is then reduced under stereoselective conditions to produce the corresponding S-configured alcohols without isolating the ketone intermediate. Controlling the stereoselectivity of the oxidation and reduction reactions by varying the amounts of acetone and 2-propanol, respectively, is the key for this stereoinversion process. This stereoinversion approach, which utilizes a single enzyme in two steps in one pot, presents a biocatalytic alternative to Mitsunobu inversion reaction.

Stereoinversion of R-configured secondary alcohols using a single enzymatic approach

255th National Meeting (2018)

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