Stereochemical Control in Microbial Reduction. 18. Mechanism of Stereochemical Control in the Diastereoselective Reduction with Baker’s Yeast

Abstract

Abstract Reduction of a variety of 2-alkyl-3-oxobutanoates with bakers’ yeast yields the corresponding l-(3S)-hydroxy esters with exclusive enantioselectivity, while the diastereoselectivity, syn/anti ratio, varies depending on the structure of the alkoxyl moiety. In order to elucidate the mechanism for this stereochemical control, oxidoreductases that reduce 2-alkyl-3-oxobutanoate have been isolated from the cells of bakers’ yeast and purified. Two dominant competing 2-alkyl-3-hydroxybutanoate oxidoreductases have been obtained: one of them reduces 2-alkyl-3-oxobutanoates stereoselectively yielding the corresponding l-syn-hydroxy esters, whereas the other affords a mixture of l-syn- and l-anti-hydroxy esters. The experimental results on stereoselectivity have nicely been simulated using kinetic parameters elucidated.