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 language | English |
|---|---|
| Pages (from-to) | 198-202 |
| Number of pages | 5 |
| Journal | Journal of Molecular Catalysis B: Enzymatic |
| Volume | 66 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Sep 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Chemoenzymatic synthesis of optically active alcohol and β-amino-acid derivative containing the difluoromethylene group
AU - Ema, Tadashi
AU - Kadoya, Taro
AU - Akihara, Kumiko
AU - Sakai, Takashi
PY - 2010/9
Y1 - 2010/9
N2 - 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.
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.
KW - β-Aminobutyric acid
KW - Asymmetric reduction
KW - Fluorine
KW - Whole-cell biotransformation
UR - http://www.scopus.com/inward/record.url?scp=77957857378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957857378&partnerID=8YFLogxK
U2 - 10.1016/j.molcatb.2010.05.009
DO - 10.1016/j.molcatb.2010.05.009
M3 - Article
AN - SCOPUS:77957857378
VL - 66
SP - 198
EP - 202
JO - Journal of Molecular Catalysis - B Enzymatic
JF - Journal of Molecular Catalysis - B Enzymatic
SN - 1381-1177
IS - 1-2
ER -