Racemisation of drug enantiomers by benzylic proton abstraction at physiological pH
- 1 January 1994
- Vol. 6 (5) , 400-404
- https://doi.org/10.1002/chir.530060507
Abstract
The enantiomers of the aromatase inhibitors 3-(4-aminophenyl)-pyrrolidine-2,5-dione (WSP-3, II), its N-pentyl derivative (III), and the antifungal econazole (IV), all possessing a benzylic proton at the chiral centre, are rapidly racemised in vitro in phosphate buffer (0.01 M) at pH 7.4 and 23°C with t½ values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)-econazole is racemised after intraperitoneal injection with t½ = 1.24h. The enantiomers of the antifungal 1-[(benzofuran-2-yl)-4-chlorophenylmethyl] imidazole (V) were stable at pH 7.4, attributable to steric hindrance to carbanion formation in the racemisation step.Keywords
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