Microbial enantioselective reduction of acetylpyridine derivatives.
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.
Kawano
Shigeru
S
Fine Chemicals Research Laboratories, Kaneka Corporation, 1-8 Miyamae, Takasago, Hyogo 676-8688, Japan.
Horikawa
Miho
M
Yasohara
Yoshihiko
Y
Hasegawa
Junzo
J
D019380:Anti-HIV Agents / Q000378:metabolism; D002175:Candida / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006865:Hydrogenation; D010084:Oxidation-Reduction; D011725:Pyridines / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism; D013237:Stereoisomerism
D019380:Anti-HIV Agents; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D005947:Glucose