Studies On The Synthesis Of Flavonoids Mannich Base And Triazole-linked Glycoconjugates

Both Flavokawain A and Flavokawain B are the predominant2′-Hydroxychalconefrom the root extracts of Kava, they have a broad spectrum of biological a ctivitiesincluding anticancer, antioxidation, antifangal, anti-imflammatory, analgesic. Andmany research showed that they were drug candidates for cancer. Apigenin andacacetin are natural flavones, they also have outstanding biological activities, such asantitumor, anticancer, immunoregulation, neuroproctive and the prevention ofhypertension. In order to study these natural flavones’ biological activities deeply andmeet the needs for the studies of new drugs, the thesis attempted to facile synthesizedan array of Mannich base and a class of flavones trizale-linked glycoconjugates fromnaringin or1,3,5-trihydroxybenzene.1、 Flavokawain A was semi-synthesized from naringin, through glycosidehydrolysis, O-methylation and ring-opening reaction. Flavokawain B was totalsynthesized from1,3,5-trihydroxybenzene, through Friedel-Crafts acetylization andO-methylation tow steps achieved2-hydroxy-4,6-trimethylacetophenone, thenClaisen-Schmidt condensation with benzaldehyde achieved this chalcone.2、The building block of Mannich base was one kind of important bioactivitymodel for drugs. And it would improved the properties of original compounds, such asbioactivity or dissolubitity. Based on Mannich reaction, fourteen chalcone mannichbase (1~14) were achieved, especially the compounds1to4and7to14were newcompounds. This aminomethylation occurred preferentially at3′-C position ofFlavokawain A and Flavokawain B.3、The naringin was a member of flavonones group and plentifully existed in therinds and follows of citrus. The amount of rhoifolin was less than naringin in nature,even though there was only one double bond difference between them. Rhoifolin wasderived from naringin’s dehydrogenation reaction. Then through O-methylation orO-benzylation and glycoside hydrolysis, rhoifolin turned to acac etin and4′-O-benzylapigenin.4、Based on ‘‘Click chemistry’’, using copper-mediated1,3-dipolar cycloadditionreactions, the propargyl derivatives of acacetin and4′-O-benzyl apigenin turned toflavones trizale-linked glycoconjugates20,21,26and27. Finally these compoundsthough deprotection achieved novel flavonoids trizale-linked glycoconjugates15,16, 17and18.This thesis synthesized fourteen Flavokawain mannich base and eight flavonoidstrizale-linked glycoconjugates, among which twenty were new compounds. Thestructures of all synthesized compounds have been confirmed by more than one of theMS,1H NMR,13C NMR and IR.