Synthesis of 4'-Hydroxypropranolol Sulfate, a Major Non-β-Blocking Propranolol Metabolite in Man

Article abstract of DOI:10.1021/jm00383a023

4'-Hydroxypropranolol sulfate (8) was recently identified as a major metabolite of propranolol (Inderal).In order to confirm the structure and to further study disposition and biological activity, he have synthesized 8 with use of 1,4-naphthoquinone (1) as the starting material.Reduction and alkylation with benzyl iodide gave 4-(benzyloxy)naphthol (3).Sulfation and chlorosulfuric acid in N,N-dimethylaniline gave potassium 1-(benzyloxy)-4-naphthol sulfate (4).Catalytic hydrogenation, alkylation with <<<(trifluoromethyl)sulfonyl>oxy>methyl>oxirane (6), and amination in isopropylamine gave 8.Racemic 8 was found to be 100-1000 times less potent than racemic propranolol as a β-adrenergic receptor blocking agent in the dog.