Production of (S)-2 '-fluorophenylethan-1-ol and (S)-3 '-fluorophenylethan-1-ol by Alternaria alternata using ram horn peptone in microbial growth medium

Abstract

Enantiomerically pure, fluorinated compounds have an important role in medicinal chemistry. Alternaria alternata isolates were used for the synthesis of (S)-2'-fluorophenylethan-1-ol 1b and (S)-3'-fluorophenylethan-1-ol 2b. Biocatalytic syntheses of optically active 1b and 2b were achieved by asymmetric reduction of 2'-fluoroacetophenone la and 3'-fluoroacetophenone 2a in the batch culture of A. alternata containing ram horn peptone (RHP). The reaction conditions (pH, temperature, and agitation) that improve the conversion of the substrates were studied. The optimal reaction conditions were found as pH 6.0, agitation 250, temperature 32 degrees C and substrate 3 mmol/100 mL. The gram scale productions of 1b and 2b by the most effective biocatalyst A. alternata EBK-6 using RHP was carried out in a fermenter with 1-L working volume. The results showed that the yields with >99% enantiomeric excess (ee) of both 1b and 2b reached 75% for 1b and 66% for 2b. The concentrations of products 1b and 2b at the end of fermentation were 3.1 g/L and 2.8 g/L, respectively. As a result, 2 important chiral intermediates for the pharmaceutical industry using A. alternata EBK-6 in the submerged culture containing RHP from waste material were scaled up to gram scale with excellent ee.