Stereoselectivity of the aliphatic hydroxylation of 6-n-propylchromone-2-carboxylic acid in rat and guinea pig

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Abstract
Following administration of 6‐n‐propylchromone‐2‐carboxylic acid (6‐n‐PCCA) (500 μmol/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 metabolities with S‐α‐methoxy‐α‐(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.

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