Stereoinversion of R-Configured Secondary Alcohols Using a Single Enzymatic Approach

TitleStereoinversion of R-Configured Secondary Alcohols Using a Single Enzymatic Approach
Publication TypeJournal Article
Year of Publication2018
AuthorsMusa, MM, Karume, I, Takahashi, M, Hamdan, SM, Ullah, N
JournalChemistry Select
Start Page10205-10208

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 (TeSADH) 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.