Chemoenzymatic synthesis of fluoxetine precursors. Reduction of β-substituted propiophenones

• Biocatalytic synthesis of optically pure pharmaceutical precursors.
• Enzymatic reduction of β-substituted acetophenones.
• Endophytic microorganisms as a source of biocatalytic diversity.
• Ketone reduction vs. functional group reductive elimination.

Five endophytic yeast strains isolated from edible plants were tested in the reduction β-chloro- and β-azidopropiophenone for the preparation of optically active fluoxetine precursors. The biotransformation rendered not only the corresponding chiral γ-substituted alcohols, but also unsubstituted alcohols and ketones. The product profile was studied and a plausible mechanism for the reductive elimination of the β-functional group is proposed.

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