title: [Synthesis of metabolites of bicyclol].
abstract: Bicyclol is a new generation of anti-hepatitis drug with China's own intellectual property rights. The chemical structure of bicyclol is new and original. Pharmacological research showed that it has high clinical efficacy in treating chronic hepatitis (HBV) patients and lower side effects. Two metabolites of bicyclol have been isolated: M2 (4-hydroxy-4'-methoxy-5, 6, 5', 6'-bis (methylenedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl) and M3 (4'-hydroxy-4-methoxy-5, 6, 5', 6'-bis (methyl enedioxy)-2-hydroxylmethyl-2'-methoxycarbonyl biphenyl). To further study the mechanism, safety, and effectiveness of bicyclol, the M2 and M3 have been total synthesized. The synthesis route is as following: the carboxyl and phenolic hydroxyl group of the aromatic bromide had been separately protected by bromobenzyl, coupling through the intermolecular asymmetric Ullmann reaction and then catalyst hydrogenated, borane reducted, two metabolites of bicyclol M2 and M3 were obtained. The structures were determined by IR, 1H NMR, HRMS. Comparison of hepatoprotective activity of bicyclol and the two metabolites on experimental liver injury, the potency of the metabolites were lower than that of bicyclol.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Chun-zhen
authors.initials: CZ
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism*; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology; D051379:Mice
chemical_list: C542805:4'-hydroxy-4-methoxy-5,6,5',6'-bis(methylenedioxy)-2-hydroxymethyl-2'-methoxycarbonylbiphenyl; C542804:4-hydroxy-4'-methoxy-5,6,5',6'-bis(methylenedioxy)-2-hydroxymethyl-2'-methoxycarbonylbiphenyl; D052117:Benzodioxoles; D001713:Biphenyl Compounds; C477843:bicyclol; D000410:Alanine Transaminase