TY - JOUR
T1 - 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
AU - Asami, Kento
AU - Machida, Takuya
AU - Jung, Sonna
AU - Hanaya, Kengo
AU - Shoji, Mitsuru
AU - Sugai, Takeshi
N1 - Funding Information:
We acknowledge the generous gift of lipases, from Amano Enzyme Inc. for PS-IM and Novozymes Japan for Novozym 435. S.J. thanks Profs. Emi Nakashima and Hisakazu Ohtani for the opportunity of research activity during overseas clinical rotation program at Keio University, under the terms of a mutual student exchange agreement between Keio and University of North Carolina Eshelman School of Pharmacy Chapel Hill, NC, USA, in June, 2012. This work was supported both by a Grant-in-Aid for Scientific Research (No. 23580152 ) and Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and acknowledged with thanks.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Hydrolysis
KW - Lipase
KW - Reduction
KW - Whole-cell biocatalyst
KW - Yeast
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U2 - 10.1016/j.molcatb.2013.08.003
DO - 10.1016/j.molcatb.2013.08.003
M3 - Letter
AN - SCOPUS:84883162135
SN - 1381-1177
VL - 97
SP - 106
EP - 109
JO - Journal of Molecular Catalysis B: Enzymatic
JF - Journal of Molecular Catalysis B: Enzymatic
ER -