ISSN:
0899-0042
Keywords:
product enantioselectivity
;
aliphatic hydroxylation
;
6-n-propylchromone carboxylic acid
;
chiral HPLC
;
chiral shift 1H-NMR
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
6-n-Alkylchromone-2-carboxylic acids are metabolized solely by aliphatic oxidation. In the rabbit, the 6-n-propyl congener (PCCA) undergoes ω-1 hydroxylation exclusively. Following administration of PCCA to female Dutch rabbits (500 μmol/kg), some 77% of the dose was excreted in the urine, 41% as PCCA and 36% as 6-(2'-hydroxy-n-propyl)chromone-2-carboxylic acid. Since this metabolite is chiral, we have examined the stereochemistry of the excreted material. Diastereoisomeric (as camphanate and α-methoxy-α-(trifluoromethyl)phenylacetate esters) and direct chiral HPLC and chiral lanthanide shift NMR have each shown the S:R ratio of the excreted metabolite to be 76:24. When rabbits were dosed with the racemic metabolite, excretion of the compound was not stereoselective. The regio- and stereo-selectivity of the aliphatic hydroxylation of PCCA are thus reflections of the selectivities of the enzyme systems responsible for its formation and suggest PCCA to be an appropriate probe compound for the study of prochiral-chiral hydroxylations.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530040103
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