Stereoselective reduction of thiocarbonyl compounds with baker's yeast

Abstract

Alkyl esters of 3-thioxo-butanoic, -pentanoic and -hexanoic acid, 2-thioxo-1-cyclopentanecarbooxylic acid ethyl ester, and 2-octanethione have been reduced with baker's yeast to give optically active thiols. The reductions parallel those of the oxygen analogues with respect to rate and diastereo- and enantioselectivity but, generally, the enantiomeric excess (ee) values are smaller. The influence of experimental variables such as substrate concentration, physiological condition of the yeast (resting/fermenting, fresh/dry/frozen), substrate modification, and addition of inhibitors on stereoselectivity has been studied. The formation of S-products was favoured by small substrate concentrations, use of dry or frozen yeast, and by addition of R-enzyme inhibitors (ethyl acrylate and biacetyl). The yields of thiol products are limited by extensive hydrolysis of the thioxo groups of all substrates used. In order to make meaningfill comparisons of enantiomeric preferences in baker's yeast reduction of different substrates it is suggested that the maximum ee values reached below certain (substrate dependent) substrate/yeast ratios are used.