Preparation of Both Enantiomers of Ethyl 3-Hydroxybutanoate by Microbial Methods

Both enantiomers of ethyl 3-hydroxybutanoate which are useful chiral starting materials for the synthesis of natural products containing CH₃CH(OH)CH₂R group have been prepared in a 3~18 g scale by microbial methods. Ethyl acetoacetate was enantio-selectively reduced to the 5-enantiomer by baker's yeast (in 83~90% e. e.) and by high temperature yeast (in 96% e. e., see Table 3). Asymmetric reductions by several brewer's yeasts (in 43~92% e. e.) and by commercially available HLADH, YADH (in 100% e. e.) gave also the 5-enantiomer. The R-enantiomer was prepared from poly (3-hydroxybutanoate) (PHB) produced by Zoogloea rami-gera, in 100% e. e. Their optical purities were determined by the HPLC analyses of the corresponding MTPA esters.