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
N1 - Funding Information:
We thank Dr. H. Amii (Kobe University) and Dr. M. Kuroboshi (Okayama University) for valuable advice on the synthesis of difluorinated compounds. We also thank Daicel Chemical Industries for providing us with Chiralscreen OH. This work was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JSPS). We are grateful to the SC-NMR Laboratory of Okayama University for the measurement of NMR spectra.
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 - Asymmetric reduction
KW - Fluorine
KW - Whole-cell biotransformation
KW - β-Aminobutyric acid
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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 -