Different behavior toward racemization in basic media from chiral analogs of clofibric acid, the active metabolite of the antilipidemic drug clofibrate

Some chiral analogs of clofibric acid, the active metabolite of the antilip idemic drug clofibrate, show different configurational stability in basic c onditions. Also, extensive racemization occurs when the corresponding optic ally active acid chlorides are treated with 3 alpha -tropanol, whereas no r acemization takes place with 3 alpha -tropanol as hydrochloride salt and wi th 3 beta -tropanol and 1-methyl-4-hydroxy-piperidine as either the free ba se or hydrochloride salt. For these aminoalcohols, experimental evidence su pports the hypothesis that a ketene intermediate is involved in the racemiz ation process. Formation of intramolecular hydrogen bond is evoked to expla in the different ability of aminoalcohols to induce ketene formation and co nsequent racemization. (C) 2000 Wiley-Liss, Inc.