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. 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.
Feske
Brent D
BD
Department of Chemistry, University of Florida, 127 Chemistry Research Building, Gainesville, Florida 32611, USA.
Kaluzna
Iwona A
IA
Stewart
Jon D
JD
D002384:Catalysis; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013237:Stereoisomerism
D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; D005982:Glutathione Transferase; D017239:Paclitaxel