Microbial Enantioselective Reduction of Acetylpyridine Derivatives

Abstract

  The microbial enantioselective reduction of acetylpyridine derivatives was studied. Many microorganisms were found to reduce 5-acetylfuro[2,3-c]pyridine (AFP) to (S)-5-(1-hydroxyethyl)furo[2,3-c]-pyridine (FPH). Candida maris IFO10003 reduced AFP to (R)-FPH with high enantioselectivity. The microbial reduction reaction was optimized. The aeration conditions and glucose concentration affected the yield and stereoselectivity. The cells accumulated 17.5 g/l (107 mM) of (R)-FPH with a 99% yield and 97% enantiomeric excess (e.e.). A cell-free extract of C. maris accumulated 91.5 g/l (559 mM) with over 99% e.e. with enzymatic NADH regeneration. (R)-FPH is an important intermediate for the synthesis of HIV reverse-transcriptase inhibitor, and other optically active 1-(pyridyl)ethanol derivatives are versatile chiral building blocks for asymmetric synthesis.