title: Synthesis of 4'-hydroxypropranolol sulfate, a major non-beta-blocking propranolol metabolite in man.
abstract: 4'-Hydroxypropranolol sulfate was recently identified as a major metabolite of propranolol (Inderal). In order to confirm the structure and to further study disposition and biological activity, we have synthesized 8 with use of 1,4-naphthoquinone as the starting material. Reduction and alkylation with benzyl iodide gave 4-(benzyloxy)naphthol. Sulfation and chlorosulfuric acid in N,N-dimethylaniline gave potassium 1-(benzyloxy)-4-naphthol sulfate. Catalytic hydrogenation, alkylation with [[[(trifluoromethyl)sulfonyl]oxy]methyl]oxirane, and amination in isopropylamine gave 8. Racemic 8 was found to be 100-1000 times less potent than racemic propranolol as a beta-adrenergic receptor blocking agent in the dog.
authors.forename: J E
authors.initials: JE
authors.lastname: Oatis
authors.forename: T
authors.initials: T
authors.lastname: Walle
authors.forename: H B
authors.initials: HB
authors.lastname: Daniell
authors.forename: T E
authors.initials: TE
authors.lastname: Gaffney
authors.forename: D R
authors.initials: DR
authors.lastname: Knapp
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; C040851:4'-hydroxypropranolol sulfate ester; D011433:Propranolol