Stereoselectivity of the aliphatic hydroxylation of 6-n-propylchromone-2-carboxylic acid in rat and guinea pig.
Following administration of 6-n-propylchromone-2-carboxylic acid (6-n-PCCA) (500 mumol/kg) to male rats, three metabolic products were detected and isolated from the 0-24 h urine. All were identified as resulting from oxidation exclusively along the 6-n-propyl moiety. Some 66% of the dose was excreted in the 0-24 h urine, 55% of which was 6-PCCA, with 15% as (6-1'-hydroxypropyl)chromone-2-carboxylic acid (6-1'-HPCCA), 22% as 6-(2'-hydroxypropyl)chromone-2-carboxylic acid (6-2'-HPCCA), and 4% as 6-3'-carboxypropyl)chromone-2-carboxylic acid (6-3'-CPCCA). Derivatization of the methyl esters of the hydroxylated metabolites with S-alpha-methoxy-alpha-(trifuloromethyl)-phenylacetyl chloride (Mosher's reagent) allowed the evaluation of urinary enantiomeric composition by HPLC and assignment of their absolute configurations by NMR. This was found to be 90:10 (R/S) for 6-2'-HPCCA, and 7:93 (R/S) for 6-1'-HPCCA. When rats were dosed with the racemic 1'- and 2-hydroxy metabolites; no stereoselective metabolism or excretion was observed. Administration of 6-n-PCCA to male guinea pigs revealed that this species was unable to metabolise this compound.
Darbyshire
J F
JF
Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.
Caldwell
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000378:metabolism* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006900:Hydroxylation; D008297:Male; D008745:Methylation; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013237:Stereoisomerism
D002867:Chromones; C075943:6-propylchromone-2-carboxylic acid