Studies On Synthesis Of Bioactive Polymethoxyflavonoids As Well As Its Vinyl Ether Derivatives

As a class of natural products, polymethoxyflavonoids(PMFs) distribut widely in citrus plants, and are regarded to be one of the potent ingredients of some medicinal plants due to a variety of biological activities. In order to research their biologial activities and further application in new drug research and development, this thesis was aimed at the synthesis and structural modification of PMFs.1. A series of multi-methoxy chalcone compounds were synthesized. First, starting from resorcinol, the 2-hydroxy-3,4,5,6-tetramethoxy acetophenone(6) was synthesized through bromination, methylation, Williamson ether synthesis and Friedel-Crafts acylation. Then the methoxy substituting aromatic aldehyde(10a) and the benzyl protecting aromatic aldehydes(10b,10c,10d) were synthesized from the commercial anillin and p-hydroxybenzaldehyde through bromination, aromatic nucleophilic substitution, methylation and benzyl protection. Four kinds of chalcones (11a-11d) were synthesized through aldol condensation between compound(6) and substituted aromatic aldehydes(10a-10d) under a basic condition, and then the products were converted to four kinds of dihydrochalcones(12a-12d) through reduction and the remove of benzyl protecting groups by using H2/Pd-C. Compounds (11b) and (12a-12d) have been not reported in literatures.2. A series of PMFs were synthesized. The said multi-methoxy chalcones(11a-11d) were converted to flavanones(13a-13d) through cyclization by using the weak alkaline of acetate-ethanol. And the obtained flavanones were oxidized to PMFs(14a-14d) by 2,3-dichloro-5,6-dicyanobenzoquinone(DDQ)-dioxane or iodine-pyridine. Then in the Aluminum chloride/anhydrous acetonitrile system, the compounds(13a,13c,14a,14c, 14d) were converted to 5-hydroxy polymethoxy flavonoids(15a,15c,17a,17c,17d), which might have stronger biological activity, through selective demethylation. Moreover, the benzyl protecting groups in compounds (13b,13c,14b,14c,14d) were removed to synthesize polymethoxyflavonoids compounds (16b,16c,18b,18c,18d) by using the palladium-carbon catalyst and hydrogen conditions. Compounds(13b), (14b), (16b), (16c) and (18b) have been not reported in literatures3. The 4'-OH or 5-OH of the synthesized PMFs were replaced by a series of other functional group. Compounds (17c),(17d),(18c),(18d), which have free phenolic hydroxy groups, were treated with prenyl bromide or trans, trans-farnesyl bromide and anhydrous potassium carbonate in anhydrous acetone. And then nine polymethoxyflavonoids-O-prenyl and-O-farnesyl derivatives(19)～(27) were synthesized. All of compounds(19)～(27) have been not reported in literatures.4. All of the synthesized compounds have been confirmed by 1H NMR, MS and IR.