Study On The Synthesis Of Norathyriol And Its Analogues

Norathyriol(1,3,6,7-tetrahydroxyxanthone), one of the dibenzo-y-pyrone, is isolated from several plants including mango, Hypericum elegans, and Tripterospermum lanceolatum. Norathyriol has been reported to have a widely range of biological and pharmacological properties such as anti-inflammatory, antitumor, inhibits P-glycoprotein activity, antioxidant and inhibits protein kinase C activity. And the analogues of norathyriol also was found to have a large variety of pharmacological activities.In this paper, we have designed a new route which more efficient for the synthesis of norathyriol. We have synthesized thirty-five compounds, twelve of them are xanthones. Most of their chemical structures have been characterized by means of1H NMR spectrum,13C NMR spectrum, MS spectrum and IR. It was a good preparation to the structure and activity relationship (SAR) study of norathyriol analogues.1. The synthesis of norathyriolIn our study, a mixture of phloroglucin and2-hydroxy-4,5-dimethoxybenzoic acid were heated in the presence of phosphoric anhydride and methylsulphonicacid, which was followed by totally demethylation to obtain norathyriol. The2-hydroxy-4,5-dimethoxybenzoic acid was obtained by the bromination, methoxylation, Vilsmeier-Haack reaction, oxidation, and selective demethylation of1,2-dimethoxybenzene.Other total synthesis routes of norathyriol were also studied by us.2. The synthesis of norathyriol analoguesMethod Ⅰ:Monosubstituted salicylic acid (2-hydroxy-3-methoxybenzoic acid,2-hydroxy-4-methoxybenzoic acid,2-hydroxy-5-methoxybenzoic acid, and2-hydroxy-3-methoxybenzoic acid and phloroglucin were heated together in the presence of phosphoric anhydride and methylsulphonic acid, which was also followed by demethylation to obtain xanthones respectively.Method II:2-bromo-benzoci acid reacted with1,2,3-trimethoxybenzene via Friedel-Crafts acetylation, selective demethylation, cyclization and totally demethylation to obtain3,4-dihydroxyxanthone.