ISSN:
0899-0042
Keywords:
enantiomers
;
nonchiral chromatography
;
palmitoyl coenzyme A oxidation
;
plasticizer
;
rat hepatocytes primary culture
;
racemate
;
resolution
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The stereoselectivity of the peroxisome proliferation potency of 2-ethylhexanoic acid (2-EHA), a metabolite of the plasticizer di-(2-ethylhexyl) adipate, was investigated in vitro. The enantiomers of 2-EHA were prepared via the semipreparative HPLC resolution of their diastereoisomeric (+)-(R)-1-phenylethylamine derivatives and the subsequent hydrolytic cleavage. Monolayers of hepatocytes were incubated 3 days with solutions of ( - )-(R), (+)-(S), and (±)-2-EHA. The peroxisome proliferation potency was measured by means of determination of the peroxisomal palmitoyl coenzyme A oxidation. The theoretical induction component due to each enantiomer were calculated from the experimental data considering the enantiomeric purities of the acids. The (+)-(S)-enantiomer was found to be the most potent inducer, e.g., the eutomer, while the ( - )-(R) was the distomer. The eudismic ratio was about 1.6 and the racemic mixture exhibited an intermediary potency. These results, obtained in vitro in conditions avoiding confounding factors such as pharmacokinetics, suggest that the peroxisome proliferation induced by 2-ethylhexanoic acid is a stereoselective phenomenon. © 1992 Wiley-Liss, Inc.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530040804
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