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

Kento Asami, Takuya Machida, Sonna Jung, Kengo Hanaya, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)106-109
Number of pages4
JournalJournal of Molecular Catalysis B: Enzymatic
Volume97
DOIs
Publication statusPublished - 2013

Fingerprint

Williopsis
Glycerol
Terbutaline
Solubility
Prodrugs
Recycling
Substrates
Carbon
Alcohols
Water
Crystalline materials
bambuterol

Keywords

  • Hydrolysis
  • Lipase
  • Reduction
  • Whole-cell biocatalyst
  • Yeast

ASJC Scopus subject areas

  • Biochemistry
  • Bioengineering
  • Catalysis
  • Process Chemistry and Technology

Cite this

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title = "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",
abstract = "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.",
keywords = "Hydrolysis, Lipase, Reduction, Whole-cell biocatalyst, Yeast",
author = "Kento Asami and Takuya Machida and Sonna Jung and Kengo Hanaya and Mitsuru Shoji and Takeshi Sugai",
year = "2013",
doi = "10.1016/j.molcatb.2013.08.003",
language = "English",
volume = "97",
pages = "106--109",
journal = "Journal of Molecular Catalysis - B Enzymatic",
issn = "1381-1177",
publisher = "Elsevier",

}

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

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 - Article

VL - 97

SP - 106

EP - 109

JO - Journal of Molecular Catalysis - B Enzymatic

JF - Journal of Molecular Catalysis - B Enzymatic

SN - 1381-1177

ER -