Stereoselective reduction of acetohexamide in cytosol of rabbit liver.
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 (diasteromer) derived by the reaction of (-)-hydroxyhexamide with (R)-(+)-alpha-methoxy-alpha-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.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Kojima
Y
Y
Higuchi
T
T
Akita
H
H
Oishi
T
T
Otagiri
M
M
D000092:Acetohexamide / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D013237:Stereoisomerism; D000096926:Benzenesulfonamides
D000092:Acetohexamide; D000429:Alcohol Oxidoreductases; C064152:acetohexamide reductase; C020362:hydroxyhexamide; D000096926:Benzenesulfonamides