Stereoselective Reduction of Acetohexamide in Cytosol of Rabbit Liver

Search this Article

Author(s)

    • IMAMURA Y.
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)
    • KOJIMA Yuichiro
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)
    • HIGUCHI Toshiyuki
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)
    • AKITA Hiroyuki
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)
    • OISHI Takeshi
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)
    • OTAGIRI Masaki
    • Faculty of Pharmaceutical Sciences, Kumamoto University:Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research (Riken Institute)

Abstract

The stereoselective reduction of acetohexamide, an oral antidiabetic drug, was studied by using the cytosol of rabbit liver. A major metabolite of acetohexamide was isolated in 41.5% yield from the enzyme reaction mixture, and identified as (-)-hydroxyhexamide by techniques including the melting point, thin-layer chromatography, infrared spectrometry and optical rotation. The enantiomeric purity of (-)-hydroxyhexamide was determined on the basis of the proton nuclear magnetic resonance (400 MHz) spectrum of ester (diastereomer) derived by the reaction of (-)-hydroxyhexamide with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride. The (-)-hydroxyhexamide isolated from the enzyme reaction mixture was almost 100% in that enantiomeric form. The metabolic reduction of acetohexamide in the cytosol of rabbit liver appeared to be catalyzed by some enzymes with the same stereoselectivity.

Journal

  • J. Pharmacobio-Dyn.

    J. Pharmacobio-Dyn. 12, 731-735, 1989

    The Pharmaceutical Society of Japan

Cited by:  1

Codes

  • NII Article ID (NAID)
    110003663027
  • NII NACSIS-CAT ID (NCID)
    AA00704585
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    0386846X
  • Data Source
    CJPref  NII-ELS 
Page Top