Chemoenzymatic synthesis of optically active alcohol and β-amino-acid derivative containing the difluoromethylene group

Tadashi Ema, Taro Kadoya, Kumiko Akihara, Takashi Sakai

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The bioreduction of α,α-difluorinated ketones, ethyl 2,2-difluoro-3-oxobutanoate (2a) and 2,2-difluoro-1-phenyl-1,3-butanedione (2b), with cells of recombinant Escherichia coli overproducing SCR (Saccharomyces cerevisiae carbonyl reductase from bakers' yeast) and GDH (glucose dehydrogenase from Bacillus megaterium) gave enantiomerically pure alcohols, ethyl (S)-2,2-difluoro-3-hydroxybutanoate ((S)-1a) and (S)-2,2-difluoro-3-hydroxy-1- phenyl-1-butanone ((S)-1b), respectively, in the presence of NADP+ and glucose in buffer. The reductions of 2a and 2b proceeded completely at the substrate concentrations of 0.4 M (67 g/L) and 1.0 M (200 g/L), respectively. The opposite enantiomers (R)-1a and (R)-1b were also produced by enzyme E039 (a mixture of carbonyl reductase and formate dehydrogenase) contained in Chiralscreen OH (Daicel Chemical Industries) in the presence of NADH and sodium formate in buffer. Enantiomerically pure (S)-1a was converted by organic synthetic methods into an α,α-difluorinated derivative of (R)-β-aminobutyric acid (BABA) in three steps.

Original languageEnglish
Pages (from-to)198-202
Number of pages5
JournalJournal of Molecular Catalysis B: Enzymatic
Volume66
Issue number1-2
DOIs
Publication statusPublished - Sep 2010

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Alcohol Oxidoreductases
formic acid
Yeast
Glucose
Saccharomyces cerevisiae
Amino acids
Buffers
Alcohols
Formate Dehydrogenases
Glucose 1-Dehydrogenase
Butanones
Bacillus megaterium
Derivatives
Aminobutyrates
Chemical Industry
Amino Acids
Enantiomers
Bacilli
Chemical industry
Ketones

Keywords

  • β-Aminobutyric acid
  • Asymmetric reduction
  • Fluorine
  • Whole-cell biotransformation

ASJC Scopus subject areas

  • Biochemistry
  • Bioengineering
  • Catalysis
  • Process Chemistry and Technology

Cite this

Chemoenzymatic synthesis of optically active alcohol and β-amino-acid derivative containing the difluoromethylene group. / Ema, Tadashi; Kadoya, Taro; Akihara, Kumiko; Sakai, Takashi.

In: Journal of Molecular Catalysis B: Enzymatic, Vol. 66, No. 1-2, 09.2010, p. 198-202.

Research output: Contribution to journalArticle

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AB - The bioreduction of α,α-difluorinated ketones, ethyl 2,2-difluoro-3-oxobutanoate (2a) and 2,2-difluoro-1-phenyl-1,3-butanedione (2b), with cells of recombinant Escherichia coli overproducing SCR (Saccharomyces cerevisiae carbonyl reductase from bakers' yeast) and GDH (glucose dehydrogenase from Bacillus megaterium) gave enantiomerically pure alcohols, ethyl (S)-2,2-difluoro-3-hydroxybutanoate ((S)-1a) and (S)-2,2-difluoro-3-hydroxy-1- phenyl-1-butanone ((S)-1b), respectively, in the presence of NADP+ and glucose in buffer. The reductions of 2a and 2b proceeded completely at the substrate concentrations of 0.4 M (67 g/L) and 1.0 M (200 g/L), respectively. The opposite enantiomers (R)-1a and (R)-1b were also produced by enzyme E039 (a mixture of carbonyl reductase and formate dehydrogenase) contained in Chiralscreen OH (Daicel Chemical Industries) in the presence of NADH and sodium formate in buffer. Enantiomerically pure (S)-1a was converted by organic synthetic methods into an α,α-difluorinated derivative of (R)-β-aminobutyric acid (BABA) in three steps.

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