Study On Synthesis And Activity Evaluation Of Natural Aspidin BB And Prenyl Flavonoids

Naturally occurring compounds have shown a diverse range of biological activities.However,they are often difficult to large-scale development and extensive use because of their limited resources,low content,complicated purification,complex structures and so on.Our previous study found that aspidin BB and prenylated flavonoids exhibited potent biological activity.In order to further explore the pharmacological activities of these two kinds of compounds,the total synthesis of aspidin BB and prenylated flavonoids as well as their derivatives were investigated.The antitumor and a-glucosidase inhibitory activity of aspidin BB and prenylated flavonoids were studied,respectivity.This research may establish foundation for the discovery of these kinds of new drugs.In this study,the total synthesis of aspidin BB was reported for the first time by 13 steps in 12.6%overall yields,strating from phloroglucinol.A series of derivatives of aspidin BB were also synthesized.The key steps include Vilsmeier reaction,Friedel-Crafts acylation,NaBH3CN reduction,selective protection and deprotection of hydroxylgroups.In addition,the natural prenylated flavonoids were synthesized with the key steps including hydrolysis reaction,Mitsunobu reaction and Cope rearrangement.We optimized the synthesis of natural 8-prenylquercetin/naringenin,and resolved the problem of high cost of Eu(fod)3 catalyst.It was the first time to report total synthesis the natural 8-gernaylquercetin/naringenin,and three new compounds including 6,8-diprenylquercetin,6,8-digernayl quercetin and 6,8-digermayl naringenin.Antitumor activity of aspidin BB and its derivatives were tested.The results showed that the inhibitory activity of aspidin BB was potent against several tumor cells,among of which inhibitory activity against HepG2 is IC50 0.53 ?M.The a-glucosidase inhibitory activity of prenyl flavonoids were evaluated.The results exhibited that the prenyl and gernayl flavonoids showed better inhibitory activity than that of flavonoids mother core.The inhibition of di-geranyl/prenyl flavonoids were higher than that of mono-geranyl/prenyl counterparts.