Enantiodivergent, biocatalytic routes to both taxol side chain antipodes.

[Reaction: see text]. Two enantiocomplementary bakers' yeast enzymes reduced an alpha-chloro-beta-keto ester to yield precursors for both enantiomers of the N-benzoyl phenylisoserine Taxol side chain. After base-mediated ring closure of the chlorohydrin enantiomers, the epoxides were converted directly to the oxazoline form of the target molecules using a Ritter reaction with benzonitrile.

Stereoselective, biocatalytic reductions of alpha-chloro-beta-keto esters.

Eighteen known and putative reductases from baker's yeast (Saccharomyces cerevisiae) were tested for the ability to reduce a series of alpha-chloro-beta-keto esters. In nearly all cases, it was possible to produce at least two of the four possible alpha-chloro-beta-hydroxy ester diastereomers with high optical purities. The utility of this approach was demonstrated by reducing ethyl 2-chloroacetoacetate to the corresponding syn-(2R,3S)-alcohol on a multigram scale using whole cells of an Escherichia coli strain overexpressing a single yeast reductase identified from the screening studies.

Systematic investigation of Saccharomyces cerevisiae enzymes catalyzing carbonyl reductions.

Eighteen key reductases from baker's yeast (Saccharomyces cerevisiae) have been overproduced in Escherichia coli as glutathione S-transferase fusion proteins. A representative set of alpha- and beta-keto esters was tested as substrates (11 total) for each purified fusion protein. The stereoselectivities of beta-keto ester reductions depended both on the identity of the enzyme and the substrate structure, and some reductases yielded both L- and D-alcohols with high stereoselectivities.