Biotransformation with a New Acinetobacter sp. Isolate for Highly Enantioselective Synthesis of a Chiral Intermediate of Miconazole

Abstract

(R)-2-Chloro-1-(2,4-dichlorophenyl) ethanol is a chiral intermediate of the antifungal agent Miconazole. A bacterial strain, ZJPH1806, capable of the biocatalysis of 2-chloro-1-(2,4-dichlorophenyl) ethanone, to (R)-2-chloro-1-(2,4-dichlorophenyl) ethanol with highly stereoselectivity was isolated from a soil sample. It was identified as the Acinetobacter sp., according to its morphological observation, physiological-biochemical identification, and 16S rDNA sequence analysis. After optimizing the key reaction conditions, it was demonstrated that the bioreduction of 2-chloro-1-(2,4-dichlorophenyl) ethanone was effectively transformed at relatively high conversion temperatures, along with glycerol as cosubstrate in coenzyme regeneration. The asymmetric reduction of the substrate had reached 83.2% yield with an enantiomeric excess (ee) of greater than 99.9% at 2 g/L of 2-chloro-1-(2,4-dichlorophenyl) ethanone; the reaction was conducted at 40 °C for 26 h using resting cells of the Acinetobacter sp. ZJPH1806 as the biocatalyst. The yield had increased by nearly 2.9-fold (from 28.6% to 83.2%). In the present study, a simple and novel whole-cell-mediated biocatalytic route was applied for the highly enantioselective synthesis of (R)-2-chloro-1-(2,4-dichlorophenyl) ethanol, which allowed the production of a valuable chiral intermediate method to be transformed into a versatile tool for drug synthesis.