Gram‐scale synthesis of (S)‐1‐(thiophen‐2‐yl)ethanol in high enantiomeric purity under Enterococcus faecium BY48 biocatalysts

Abstract

Sulfur‐containing chiral heterocyclic secondary alcohols are relevant intermediates in the preparation of enantiomerically pure compounds endowed with biological activity. In this report, we evaluated the reductive potential of different lactic acid bacteria as whole‐cell biocatalysts of the enantioselective reduction of 1‐(thiophen‐2‐yl)ethanone (1). Enterococcus faecium BY48, isolated from boza, a cereal‐based fermented beverage, was found to be the best biocatalyst in our initial investigations. Using whole‐cell preparations of E. faecium BY48, we then systematically analyzed the reaction parameters (pH, incubation period, agitation speed, and temperature) to optimize the yield, the enantiomeric excess (e. e.), and the conversion leading to (S)‐1‐(thiophen‐2‐yl)ethanol [(S)‐2]. The target derivative, which is a precursor in the synthesis of biologically active chiral compounds, was obtained in enantiomerically pure form, gram‐scale amounts, and high yield. This is also the first report that the manufacture of (S)‐2 in excellent conversion, yield, enantiopure form, and gram scale used whole‐cell biocatalyst. This whole‐cell E. faecium BY48 biocatalyzed reaction is a clean, environmentally friendly, and cost‐effective process, representing a valuable alternative to chemical catalysis or previously reported biocatalytic procedures in the preparation of (S)‐2.

Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

“…Engin Sahin further reported the bioreduction of 1-(thiophen-2-yl)ethanone to ( S )-1-(thiophen-2-yl)ethanol using the lactic acid bacterium Enterococcus faecium BY48. 50 This method offered an alternative green approach to the chemical synthesis of sulfur-containing chiral heterocyclic secondary alcohols. The same research group reported the bioreduction of a variety of prochiral ketones to their respective ( R )-alcohols using whole cells of Lactobacillus kefiri P2.…”

“…The final mutant, I91V/I187S/I188L/Q191N/F205A (F12), showed 183-fold enhanced specific activity. A preparative scale reduction of 49 at a substrate concentration of 20 g L −1 by wet cells coexpressing RasADH F12 and GDH produced (13R,17S)-ethyl secol (50) with 99% conversion in 6 h, with >99.5% stereoselectivity and a yield of 94%.…”