Study On Total Synthesis Of Prenylated Flavonoids And Its Biological Activity

Prenyl present in the C6-C3-C6 nucleus structure of flavonoid in medicinal plants. Prenyl flavonoid known as a natura l defensin and it plays a good physiological regulation when the plants suffered external factors. Prenyl flavonoids is a typically flavonoid in medicinal plants, present widely in nuture. Isopentenyl includedmonoor multiple connection isopentenyl group and benzodizepines dimethyl furan flavonoids. The presence of isopentenyl group will enhance the lipophilic of the compounds greatly, such compounds can pass through the cell membrane lipid-soluble more easily and combine with target protein, Prenyl flavonoids played a certain biological activity. Isopentenyl presence will enhance the functional activity of the compounds such as anti-tumor, anti- inflammatory, immune regulation.Many isolated prenyl flavonoids was extracted through naturel medicianl plants by scholars, and many study of the biologual activity about theprenyl flavonoids made good progress. In order to meet the demand of studies about prenyl flavonoids, the work of artificial synthesis of isoamyl alkenyl flavonoids has been carried out. This project aims to develop a meaningful, easy operation, cheap raw material, good yield, widely applicationroute, it could used in industrial production.With mlti- hydroxyl groups of 2-OH acetophenone as the starting material, through Friedel–Crafts alkylation reaction to adduct isoamyl alkenyl, phenol hydroxyl was protected with chlorine methyl ether selectively, then through aldol condensation with benzaldehydeto afford intermediates-chalcone, isoamyl alkenyl dihydrogen flavonoids was obtained by Michael addition and deprotect. Using the total synthsis route we afford the six different pentenyl dihydrogen flavonoids.With 2,4,6-tre- hydroxy acetophenone as starting materials, through Friedel–Crafts alkylation reaction to adduct isoamyl alkenyl,phenol hydroxyl was protected with chlorine methyl ether selectively,give the flavonols by Algar–Flynn–O yamada reaction, finally to take off the protection to give two different pentenyl flavonols. The route is easy operation, good yield and wide application. On the basis of this route, we design to adduct the isoamyl alkenyl group, afford Chroman by cyclization, finally used this synthesis route to give two 2- methyl pyran truxene isoamyl alkenyl flavonols.We also synthesis a polyhydroxy isopentenyl chalcone and a prenyl ether anthracene chalcone. In order to set a control group in the study of biological activity of flavonoids, we also synthesized another two hydroxyl dihydrogen flavonoids without prenyl.The effects of Prenyl flavonoid on human breast cancer cell line MC F- 7 and human liver cancer cell Hep G2 growth and apoptosis in vitro. The results showed that four Prenyl flavonoid compounds could significantly inhibit the growth of HepG2 and three Prenyl flavonoids could significantly inhibit the growth of MCF-7.And two flavonoids without prenyl did not inhibit the growth of the canc ercell.The study showed that isopentenyl presence will enhance the functional activity of the compounds.We had synthesis 15 flavonoid compounds and 39 intermediate compounds through 4 total synthesis routs successfully. The structure of the target compound synthesized was confirmed by ¹H-NMR,¹³C-NMR and MS（ESI）.The experiment about the effect of prenyl flavonoid on human cancer cell shows that prenyl flavonoid play a biological activity in vitro.