TY - JOUR T1 - Regioisomeric products of propranolol metabolism. The monomethyl ethers of 3,4-dihydroxypropranolol and of 3,4-dihydroxypropranolol glycol. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 217 LP - 221 VL - 16 IS - 2 AU - L M Gustavson AU - W L Nelson Y1 - 1988/03/01 UR - http://dmd.aspetjournals.org/content/16/2/217.abstract N2 - Regioisomeric monomethyl ethers of the 3,4-catechol of propranolol (1) and its 3-aryloxypropane-1,2-diol (glycol) metabolite were prepared to prove the structures of these putative products of oxidative metabolism. The ring regioisomer 4-methoxy-3-hydroxypropranolol (3) was prepared from 1-acetoxy-3-acetyl-4-methoxynaphthalene (8). Baeyer-Villiger oxidation was the key step in converting the 3-acetyl functionality to the desired 3-naphthol. The ring regioisomer 4-hydroxy-3-methoxypropranolol (4) was prepared from 3-methoxy-1,4-dihydroxynaphthalene (13) by selective 1-O-acylation with trimethylacetyl chloride. 4-O-Benzylation, followed by hydrolysis, and side chain elaboration afforded the 4-O-benzyl ether of 4. Similar methods afforded glycols 5 and 6, with the side chain obtained by osmium tetroxide oxidation of an O-allyl group. GC/MS analysis using the trifluoroacetyl derivatives of these known standards showed both 3 and 4 were metabolites of 1 in the rat. From a single dose study in man, 4 was identified as a minor urinary metabolite, and both regioisomeric glycol metabolites 5 and 6 were observed. In addition, another regioisomeric hydroxymethoxyglycol metabolite was found. ER -