Stereochemical control of yeast reductions. 6. Diastereoselectivity of 2-alkyl-3-oxobutanoate oxido-reductases.

Abstract

Two L-oxido-reductases, designated as L-enzyme 1 and L-enzyme 2, purified from bakers' yeast catalyzed the reduction of 2-alkyl-3-oxobutanoates using NADPH as the coenzyme to furnish carbinols of the L-configuration ( ee = 0.98). The L-enzyme 2 (MW 36,000) has a more relaxed substrate specificity than L-enzyme 1 (MW 74,000). With the exception of 2-methyl-3-oxobutanoate, L-enzyme 1 and 2 exhibited opposite chiral preferences relative to the C-2 substituent to yield the anti(2S,3S)- and the syn(2R,3S)-isomer respectively. The degree of diastereoselectivity depends on the C-2 substituent but not on the size of the ester grouping for L-enzyme 1. In contrast, the diastereoselectivity of L-enzyme 2 is not affected by the size of C-2 alkyl substituent and ester groupings. The kinetic parameters of the purified enzymes are consistent with the stereochemical outcome of intact bakers' yeast reductions in that L-enzyme 1 is the dominant enzyme in competitive reductions.