Deracemization Of Aryl Secondary Alcohols Via Coupling Of Enantioselective Oxidation And Stereoselective Reduction With Tandem Biocatalysts

Nowadays, chiral compounds are becoming the most important building blocks in the chemical and pharmaceutical industries, for the production of chemical catalysts, flavors, agrochemicals and drugs. Especially, optically active secondary alcohols are widely used as intermediates for introducing chiral center(s) into end-products. Deracemization of racemic sec-alcohols is considered as one of the most important, fundamental and practical reactions for producing chiral sec-alcohols.Deracemization of racemic 1-phenylethanol, i.e., stereo-inversion of (R)-1-phenylethanol to (S)-1-phenylethanol, has been successfully realized via concurrent enantioselective oxidation and stereoselective reduction employing whole-cell biocatalysts of an alcohol dehydrogenase and a ketone reductase with opposite stereoselectivity in one-pot. One biocatalyst is Microbacterium oxydans ECU2010 which catalyzes stereoselective oxidation of (R)-secondary alcohols to corresponding ketones and another is Rhodotorula sp. AS2.2241 which reduces the ketones to (S)-secondary alcohols. Each of the whole-cell biocatalysts has its own in vivo cofactor regeneration system so that there is no need to add the expensive cofactor and/or the oxidoreductase for the cofactor regeneration. To explore the generality of this method, a broad range of racemic aryl secondary alcohols were efficiently deracemized to their (S)-enantiomers by combination of the two microorganisms, affording optically pure secondary alcohols in high yields (86.5-99.0%) and excellent optical purity (>99% ee). Our method represents an easy going, cheap and environmentally benign way for the biocatalytic synthesis of chiral aryl secondary alcohols from their racemates. We also explored the combination of enzymes for deracemization and stereoinversion of sencondary alcohols.