Aromatic hydroxylation of .beta.-adrenergic antagonists. Formation of 4'- and 5'-hydroxy-1-(isopropylamino)-3-[2'-(allyloxy)phenoxy]-2-propanol from oxprenolol

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Abstract
[.beta.-Adrenergic antagonists are used in a variety of cardiovascular disorders and in other disease states, including psychiatric disorders.] The metabolic aromatic hydroxylation of oxprenolol [1-(isopropylamino)-3-[2''-(allyloxy)phenoxy]-2-propanol] in rats was examined. Synthesis of the isomeric ring methoxyoxprenolols 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 Baeyer-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 4''- and 5''-hydroxyoxprenolol (4a and 5a) were present in an approximate 4:1 ratio. No 3''- or 6''-hydroxyoxprenolol was detected. The metabolites obtained from a human urine treated in the same manner gave similar results with both 4a and 5a present.

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