Reduction of 2-Substituted 3-Oxoglutarates Mediated by Baker's Yeast. Variation in Enantioselectivity without Corresponding Variation in Diastereoselectivity

Article abstract of DOI:10.1021/jo00060a048

The reduction of 2-substituted 3-oxoglutarates by yeast yields a new class of chiral building blocks, 2-allyl- and 2-propargyl-3-hydroxyglutarates.These are useful as starting points for the synthesis of, inter alia, branched chain analogs of sugars and nucleosides.When allyl is the side chain, the principal product has the absolute configuration (2S,3S), proven by correlation with a compound whose absolute configuration was established by crystallography.Several features of this yeast-mediated reduction are noteworthy.First, its diastereoselectivity is higher than its enantioselectivity, especially with the propargyl side chain.Further, with all substrates, variation in enantioselectivity is not manifested by a variation in diastereoselectivity.This example therefore serves as a warning for those using yeast-mediated reactions that diastereoselectivity cannot be accepted as a substitute for direct measurements of enantioselectivity, even with analogous substrates and similar reaction conditions.Finally, an unexpected metabolism of impurities in the starting material by the yeast made the overall transformation preparatively useful.