| Abstract
| - Baker's yeast (Saccharomyces cerevisiae) has been used to reduce a series of alkyl esters derivedfrom pyruvate and benzoylformate. Both the yield and enantioselectivities of these reductions weremaximized when methyl esters were used, and the (R)-alcohols were isolated in all instances. Yeast-mediated ester hydrolysis was a significant side reaction for products derived from long-chainalcohols. In the case of ethyl benzoylformate, the addition of methyl vinyl ketone increased theenantioselectivity of the reduction. These reductions were applied to two syntheses of the paclitaxelC13 side chain [(2R,3S)-N-benzoyl-3-phenylisoserine]. In the first, a racemic α-keto-β-azido esterwas reduced by whole cells of Baker's yeast to afford a diastereomeric mixture in which the desiredproduct predominated and could be isolated chromatographically. In the second, an easilysynthesized α-keto-β-lactam was reduced by yeast cells to afford the desired cis isomer as well asthe undesired trans diastereomer. Substituting a yeast strain deficient in fatty acid synthase inthis reduction suppressed formation of the trans diastereomer. These results suggest that a singleenzyme is responsible for both the d- and l-cis-alcohols resulting from reduction of the α-keto-β-lactam. All of the yeast strains used in this project are available commercially, and these biocatalyticreductions require only common laboratory equipment.
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