title: Chemical aspects of propranolol metabolism. Synthesis and identification of 3-(4-hydroxy-1-naphthoxy)propane-1,2-diol as a metabolite of propranolol in the dog, in man and in the rat liver 9000g supernatant fraction.
abstract: 4-Hydroxypropranolol glycol (2), a suspected metabolite of propranolol was synthesized from 4-allyloxy-1-naphthaldehyde (4). Osmium tetroxide oxidation of 4 afforded a glycol (5) and subsequent Baeyer-Villiger rearrangement afforded 2. Its presence as a biliary metabolite in a dog maintained on a constant infusion of pseudoracemic propranolol (made up of equal molar 2S-propranolol-3',3'-d2 and 2R-propranolol-d0) into the portal vein was confirmed based on GC-MS data of the TFA and TMS derivatives of the standard and biliary metabolites. Greater amounts of 2 arose from 2R-propranolol than from 2S-propranolol (1.5:1). Similarly, 2 was formed as a urinary metabolite in one subject maintained on oral propranolol, 80 mg every 6 hours. Compound 2 was also formed when propranolol and propranolol glycol were incubated in the presence of the rat liver 9000g supernatant fraction. In addition to 2, an isomeric ring-hydroxylated propranolol glycol, perhaps 7-hydroxypropranolol glycol, was formed when propranolol glycol was the substrate.
mesh_terms: D000368:Aged; D000818:Animals; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: C039899:4-hydroxypropranolol glycol; D011433:Propranolol