METABOLISM OF BETA-ADRENERGIC ANTAGONISTS - EVIDENCE FOR AN ARENE OXIDE-NIH SHIFT PATHWAY IN THE AROMATIC HYDROXYLATION OF OXPRENOLOL

The metabolic hydroxylation of 4ʹ-deuteriooxprenolol [l-(isopropylamino)-3-[2ʹ-(allyloxy)-4ʹ-deuteriophenoxy]- 2-propanol] prepared from the 4ʹ-bromo compound was examined in the rat (in vivo). GC-MS analysis of the 4ʹ- and 5ʹ-hydroxyoxprenolol obtained showed 65% retention of deuterium in each of the metabolites. The results indicate that an arene oxide-NIH shift pathway is operative in these hydroxylation processes. The equal magnitude of deuterium retention is supportive of a 4ʹ, 5ʹ-arene oxide as a major contributor to their formation. © 1979, American Chemical Society. All rights reserved.