Gas-chromatographic resolution of enantiomeric secondary alcohols. Stereoselective reductive metabolism of ketones in rabbit-liver cytosol.
Chiral secondary alcohols were treated with (S)-(-)-1-phenylethyl isocyanate. For each racemic alcohol, the resulting diastereomeric urethane derivatives were resolved on flexible fused-silica capillary GLC columns with retention times of 15 min or less. Derivatization of individual enantiomers showed that the urethane derivatives of (R)-(-)-2-octanol, (R)-(+)-1-phenylethyl alcohol, and (S)-(+)-2,2,2-trifluoro-1-phenylethanol are eluted before the corresponding diastereomers. The procedure is simple and rapid, and is suitable for the determination of the enantiomeric composition of chiral alcohols extracted from biological media. A series of aliphatic alcohols, aryl alkyl carbinols, and arylalkyl alkyl carbinols were resolved with the procedure, and the degree of resolution varied from good to excellent. Eight achiral ketones were incubated, individually, with rabbit-liver 90,000 g supernatant fractions, and the enantiomeric composition of the alcohol metabolites was determined with the GLC procedure. The reductions proceeded with high stereoselectivity to give alcohol products of 90% or greater enantiomeric purity. The reduction of 2-octanone and acetophenone gave predominant alcohols of (S)-configuration, in agreement with the Baumann-Prelog rule. The configuration of the predominant alcohols arising in the reduction of the remainder of the ketones could not be firmly established, but the evidence suggests that they are also of the (S)-configuration. Fluorine or methyl substitution in the ortho position of acetophenone produced an increase in the stereoselectivity, and the alcohol produced from ortho-methylacetophenone was enantiomerically greater than 99% pure.
D000438:Alcohols / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002849:Chromatography, Gas; D003485:Cyanates; D003600:Cytosol / Q000378:metabolism; D017953:Isocyanates; D007659:Ketones / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000438:Alcohols; D003485:Cyanates; D017953:Isocyanates; D007659:Ketones; C020790:phenylethyl isocyanate