Stereochemical control in microbial reduction .28. Asymmetric reduction of alpha,beta-unsaturated ketones with bakers' yeast

Bakers' yeast reduction of alpha,beta-unsaturated ketones affords optically active saturated ketones contaminated by allylic and saturated alcohols as minor components. Stereoselectivity of the reduction of carbon-carbon double bond strongly depends on the structure of beta-aryl substituent. The bakers' yeast reduction of beta-phenyl enones gives saturated ketones in moderate stereoselectivity. Stereoselectivity is not altered by substitution at the para-position, whereas introduction of a substituent at the ortho- or meta-position drastically improves the stereoselectivity. Deuterium-labeling experiments reveal that the enzymatic reduction of carbon-carbon double bond proceeds with formal trans-addition of hydrogens regardless the efficiency of stereoselectivity. The resulting optically active ketone was converted to the precursor of (S)-iopanoic acid, an inhibitor of thyroxine 5'-deiodinase that is a thyroid hormone-converting enzyme and an oral cholecystographic agent.