Chemo-enzymatic route for (R)-terbutaline hydrochloride based on microbial asymmetric reduction of a substituted α-chloroacetophenone derivative

To synthesize (R)-terbutaline hydrochloride, a potent β2-adrenoceptor-stimulating agent, asymmetric reduction of a substituted α-chloroacetophenone derivative with cultured whole-cell biocatalyst of the yeast Williopsis californica JCM 3600 was developed as the key reaction. The reduction proceeded by a si-facial attack of hydride in a highly enantioselective manner. Co-factor generation was enhanced by applying glycerol as the carbon source.