Biohydrogenation of unsaturated compounds by Saccharomyces cerevisiae. 1. Stereochemical aspects of the reaction and preparation of useful bifunctional chiral synthons

Ethyl 4,4-dimethoxy-3-methylbut-2-enoate (1; R = CO2Et) has been prepared as a mixture of (E)-and (Z)-isomers, the (E)/(Z) ratio depending on the base used. Each isomeric mixture of (1a) and (1b) has been used as substrate for biohydrogenation with fermenting Saccharomyces cerevisiae (baker's yeast) and the (Z)-isomer seems to be the preferred substrate. (E)-Unsaturated alcohols such as (3a) and (5d) are not reduced to the corresponding saturated hydroxy derivatives by baker's yeast. The (E)-aldehyde (3c) and its acetal (3d) are mainly reduced to the corresponding (E)-alcohol (3a), the saturated hydroxy ester (2a) being formed to a minor extent, especially with (3d). In contrast, biohydrogenation is also successful with the (E)-isomers of compounds (3e), (3f), and (3b) (R2 = alkyl or alkenyl). If the allylic oxygenated group to be reduced is not α-methyl substituted, reduction to the corresponding saturated alcohols readily occurs with the (E)-isomers as in the case of (5f). For this last biohydrogenation, the stereochemistry of the methyl-bearing carbon has been established by chemical correlations. The α,β-disubstituted allylic acetal (6a) is not biohydrogenated by the yeast, but a mixture of unsaturated hydroxy ester (6b) and γ-hydroxy lactone