Biochemical approaches to the synthesis of ethyl 5-(S)-hydroxyhexanoate and 5-(S)-hydroxyhexanenitrile

Three different biochemical approaches were used for the synthesis of ethyl 5-(S)-hydroxyhexanoate a and 5-(S)-hydroxyhexanenitrile 2. in the first approach, ethyl 5-oxo-hexanoate 3 and 5-oxo-hexanenitrile 4 were reduced by Pichia methanolica (SC 16116 to the. corresponding (S)-alcohols, ethyl (S)-5-hydroyhexanoate 1 and 5-(S)-hydroxyhexanenitrile 2, with an 80-90% yield and > 95% enantiomeric excess (e.e). In the second approach. racemic 5-hydroxyhexanenitrile 5 was resolved by enzymatic succinylation, leading to the formation of (R)-5-hydroxyhexanenitrile hemisuccinate and leaving the desired alcohol 5-(S)-hydroxyhexanenitrile 2 with a yield of 34% (50% maximum yield) and > 99% e.e. In the third approach, enzymatic hydrolysis of racemic 5-acetoxy hexanenitrile 6 resulted in the hydrolysis of the R-isomer to provide 5-(R)-hydroxyhexanenitrile. leaving 5-(S)-acetoxyhexanenitrile 7 with a 42% yield (50% maximum yield and > 99% e.e. (C) 2001 Elsevier Science Inc. All rights reserved.