Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600

To achieve the synthesis of (R)-bambuterol, a prodrug of (R)-terbutaline, asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with whole cells of Williopsis californica JCM 3600 pre-incubated on glycerol as a carbon source was examined. Initially, the insolubility of this crystalline substrate (mp 126-127 C) in the incubation broth was an obstacle that needed to be overcome. To solve the problem, the concentration of glycerol was increased to 10% during reduction. Glycerol worked well for recycling oxido-reduction cofactors and for enhancing the water solubility of the substrate. The reduction proceeded smoothly to give enantiomerically pure (R)-alcohol in 81% isolated yield.