Enantiodivergent, Biocatalytic Routes to Both Taxol Side Chain Antipodes

Two enantiocomplementary bakers' yeast enzymes reduced an α-chloro-β-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 for...

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Bibliographic Details
Published in:Journal of organic chemistry 2005-11, Vol.70 (23), p.9654-9657
Main Authors: Feske, Brent D, Kaluzna, Iwona A, Stewart, Jon D
Format: Article
Language:English
Subjects:
Catalysis
Catalysts: preparations and properties
Chemistry
Exact sciences and technology
General and physical chemistry
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Organic chemistry
Oxidoreductases - metabolism
Paclitaxel - chemical synthesis
Paclitaxel - chemistry
Preparations and properties
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - metabolism
Stereoisomerism
Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
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Summary:Two enantiocomplementary bakers' yeast enzymes reduced an α-chloro-β-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. These were hydrolyzed to the ethyl ester form of the Taxol side chain enantiomers under acidic conditions. This brief and atom-efficient route to both target enantiomers demonstrates both the synthetic utility of individual yeast reductases and the power of genomic strategies in making these catalysts available.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo0516077