Study On The Synthesis Of Norathyriol And Its Analogues

Norathyriol, also named as1,3,6,7-tetrahydroxyxanthone, is a naturally occurring polyphenolic compound which was found widespreadly in various herbal plants, such as the genus Garcinia and the Hypericum perforatum. Norathyriol has been reported to have a wide range of biological and pharmacological properties, such as antioxidant, antitumor, Antidepressant, Antiviral, as well as its natural analogues have significantly beneficial pharmacological properties.In this paper, we have studied the synthesis of Norathyriol by designing two novel routes, and all steps were optimized. Then, we also designed eight Norathyriol analogues which feature the diverse substitution of hydroxygen groups on the same mother nucleus of xanthone. We have synthesized forty-nine compounds in totally, among of which eighteen are xanthone compound, and thirteen are new compounds. Most of them were verified by1H NMR spectrum,13C NMR spectrum and MS spectrum (HRMS).Our work was composed of two sections as follows:Part One The synthesis of NorathyriolMethod A:Phenylamine and3,4-dimethoxybenzaldehyde were used as the starting materials, respectively via bromination, diazotization, diazonium reduction, methoxylation and bromination, oxidization to obtain1,3,5-trimethoxybenzene and2-bromo-4,5-dimeth-oxybenzoic acid, which were followed by Friedel-Crafts acetylation, selective demethylation, Ullmann cyclization, totally demethylation to obtain Norathyriol in a yield of62%.Method B:Norathyriol was synthesized in a high yield (36%) by a reaction sequence starting from1,2-dimethoxybenzene and1,3,5-trimethoxybenzene via Vilsmeier-Haack reaction, BCl3selective demethylation, bromination followed by cyclization reaction catalyzed by PdCl2(PPh3)2and totally demethylation.Part Two The synthesis of Norathyriol analogues 1.2-bromo-3,4,5-trimethoxybenzoic acid was used as the starting material, respectively react with1,3,5-trimethoxybenzene,1,2,4-trimethoxybenzene and1,4-dimethoxybenzene via Friedel-Crafts acetylation, selective demethylation, Ullmann cyclization, totally demethylation to obtain three Norathyriol analogues.2.2-bromo-4,5-dimethoxybenzoic acid was used as the starting material, respectively react with1,2,4-trimethoxybenzene and1,4-dimethoxybenzene via Friedel-Crafts acetylation, selective demethylation, Ullmann cyclization, totally demethylation to obtain two Norathyriol analogues.3. salicylic acid was used as the starting material, respectively react with1,3,5-trimethoxybenzene,1,2,4-trimethoxybenzene and1,4-dimethoxybenzene via Friedel-Crafts acetylation, cyclization, totally demethylation to obtain three Norathyriol analogues.