Two Classes of Enzymes of Opposite Stereochemistry in an Organism:  One for Fluorinated and Another for Nonfluorinated Substrates

• Published in: Journal of organic chemistry Vol. 65; no. 1; pp. 157 - 163
• Main Authors: Matsuda, Tomoko, Harada, Tadao, Nakajima, Nobuyoshi, Itoh, Toshiyuki, Nakamura, Kaoru
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.01.2000
• Subjects: Fluorine - metabolism; Geotrichum - enzymology; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo991283k

Reduction of methyl ketones by dried cells of Geotrichum candidum (APG4) afforded (S)-alcohols in excellent enantiomeric excess (ee), whereas the reduction of trifluoromethyl ketones gave the corresponding alcohols of the opposite configuration also in excellent ee. The replacement of the methyl moiety with a trifluoromethyl group alters both the bulkiness and the electronic properties, the effect of which on the stereoselectivity was examined. No inversion in stereochemistry was observed in the reduction of hindered ketones such as isopropyl ketone, while the stereoselectivity was inverted in the reduction of ketones with electron-withdrawing atoms such as chlorine. The mechanism for the inversion in stereochemistry was investigated by enzymatic studies. Several enzymes with different stereoselectivities were isolated; one of them catalyzed the reduction of methyl ketones, and another with the opposite stereoselectivity catalyzed the reduction of trifluoromethyl ketones. Furthermore, both APG4 and the isolated enzyme were applied to the reduction of fluorinated ketones on a preparative scale, which resulted in the synthesis of chiral fluorinated alcohols with excellent ee.