Total production of (R)-3,5-bistrifluoromethylphenyl ethanol by asymmetric reduction of 3,5-bis(trifluoromethyl)-acetophenone in the submerged culture of Penicillium expansum isolate

A total of 82 fungal isolates were screened for their ability to reduce 3,5-bis(trifluoromethyl)-acetophenone 1. Penicillium expansum was found to successfully reduce ketone 1 in the submerged culture. A second screening was performed on the active P. expansum strains identified by the first screening. A number of strains of P. expansum were found to produce (R)-3,5-bistrifluoromethylphenyl ethanol 2 with over 99% enantiomeric excess (ee) from ketone 1. The most productive strain was identified as P. expansum EBK-9, and this strain was selected for further experiments. The total production of 2 was carried out by P. expansum EBK-9 in a laboratory-scale bioreactor employing optimized conditions as determined by our experiments. P. expansum EBK-9 gave 2 with ee >99% and 76% yield. On a large scale, a total of 3.35 g/L of 2 was produced from 1 after 56 h.

Figure optionsDownload as PowerPoint slide

(R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethanolC10H8F6OEe >99 HPLC on (Chiralcel OD-H) columnSource of chirality: microbial reduction[α]D20=+16.4 (c 0.85, CHCl3)Absolute configuration: (R)Retention time: 15.6 (S), 17.6 (R)