Synthesis of 4'- and 5'-hydroxyoxprenolol:pharmacologically active ring-hydroxylated metabolites of oxprenolol.

Synthesis and preliminary pharmacological activity data for 4'- and 5'-hydroxyoxprenolol (2 and 3) are reported. The synthetic routes make use of the isomeric 2-pyranyl monoether derivatives of 4-hydroxysalicylaldehyde and 2,5-dihydroxyacetophenone. The corresponding O-allyl ethers were converted to substituted phenols by Baeyer-Villiger oxidation and the propanolamine side chain elaborated using epichlorohydrin, followed by oxirane ring opening with isopropylamine. Each of the hydroxylated metabolites is about ten times less potent than oxprenolol as an antagonist to the isoproterenol-induced relaxation of guinea pig tracheal strips.