Reduction of acetophenones with methyl fluorines and a bulky group on the aromatic ring using microorganisms and related enzymes

Whole-cell yeasts and mold-catalyzed reduction of two fluorinated acetophenone derivatives with very bulky substituents on ortho position of aromatic ring, (±)-1′-(2-tert-butyl-2-methyl-1,3-benzodioxol-4-yl)-2′,2′-difluoroethanone and (±)-1′-(2-tert-butyl-2-methyl-1,3-benzodioxol-4-yl)-2′,2′,2′-trifluoroethanone were examined. On the former substrate, Geotrichum candidum NBRC 5767 showed high re-facially selective attack of hydride, while with Pichia angusta JCM 3620, complementary si-facially selective attack proceeded. G. candidum NBRC 5767 was revealed to be potent biocatalyst which provides (1′S)-alcohols from both substrates in a highly facially selective manner. Some unknown reductases were suggested responsible for those reductions, other than so far having been reported acetophenone reductase and trifluoromethyl ketone reductase from G. candidum, comparing the results obtained by applying those enzymes.

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► Whole-cell biocatalyst-mediated reduction of two fluorinated acetophenone derivatives with very bulky substituents of aromatic ring was examined.
► Complementary facial selectivity between G. candidum and P. angusta on the attack of hydride to 1′-(2-tert-butyl-2-methyl-1,3-benzodioxol-4-yl)-2′,2′-difluoroethanone was observed.
► So far reported enzyme preparations of acetophenone reductase and trifuoromethyl ketone reductase from G. candidum were applied to the present substrates.
► The above-mentioned two enzymes were not responsible for the formation of major stereoisomers made by whole-cell biocatalyst.