AROMATIC HYDROXYLATION OF BETA-ADRENERGIC ANTAGONISTS - FORMATION OF 4' AND 5'-HYDROXY-1-(ISOPROPYLAMINO)-3-[2'-(ALLYLOXY)PHENOXY]-2-PROPANOL FROM OXPRENOLOL

The metabolic aromatic hydroxylation of oxprenolol [l-(isopropylamino)-3-[2ʹ-(allyloxy)phenoxy]-2-propanol] in rats was examined. Synthesis of the isomeric ring methoxyoxprenolols (3b-6b) was accomplished from the isomeric methoxysalicylaldehydes by O-allylation, followed by Baeyer-Villiger oxidation. The propanolamine side chain was elaborated by O-alkylation of the Bayer-Villiger product with epichlorohydrin and subsequent oxirane opening with isopropylamine. Gas chromatography-mass spectra of the trifluoroacetyl derivatives of these standards was compared with urinary metabolites obtained from the rat, after methylation with diazomethane and derivatization with trifluoroacetic anhydride. Both 4ʹ- and 5ʹ-hydroxyoxprenolol (4a and 5a) were present in an approximate 4: 1 ratio. No 3ʹ- or 6ʹ-hydroxyoxprenolol (3a and 6a) was detected. The metabolites obtained from a human urine treated in the same manner gave similar results with both 4a and 5a present. © 1979, American Chemical Society. All rights reserved.