Synthesis And Structural Modifications Of Dioscin And Solamargine

Dioscin and solamargine are spirostan saponins. Modern researches show that dioscin and solamargine have a variety of biologically activities such as antitumor, antifungal. They are the main active component of cardiovascular drug-DI’AO XIN XUE KANG and anticancer agent-Coramsine, respectively. The chemical synthesis of steroidal saponins have linear and convergent synthetic strategy. In most cases linear synthetic strategy are exploited because the glycosylation reaction of sapogenin and oligosaccharide donor in convergent synthesis lack stereoselectivity for the formation of a glycosidic bond. In this paper, we developed a protocol for the β glycosylation of chacotriosyl trichloroacetimidate and accomplished the convergent syntheses of dioscin, solamargine and their analogues.1. Syntheses of dioscin and 26-thio- and selenodioscinConvergent synthesis of dioscin was achieved by the glycosylation of the diosgenin and chacotrisyl trichloroacetimidate in the promotion fo HB(C6F5)4(0.1eq) in the BTF/tBuCN/DCM (5/1/1.3) at -20 ℃ with a ratio of α/β= 1/9.7 followed by removal of protecting groups.S and Se is the bioisosteric of O, and the organo-sulfur and selenium compounds have anticancer, antioxidation, antifungal and so on. In this section 26-thio-and selenodiosgenin were prepared from diosgenin by means of Marker reaction, hydrolysis of acetate, selective tosylation of 26-OH, displacement of tosylate with potassium thioacetate or cesium diselenide, hydrolysis of thioacetae or reduction of diselenide. Then stereoselective glycosylations of 26-thio- and selenodiosgenin and chacotrisyl trichloroacetimidate was performed in the promotion fo HB(C6F5)4(0.1eq) in the BTF/tBuCN/DCM to afford the glyosides followed by removal of the protecting groups to produce 26-thio- and selenodioscin in the yield of 48% and 27% through a total of 9 steps, respectively. and the cytotoxicities of 26-thio- and selenodioscin were tested.2. Syntheses of solamargine and its analoguesThe glycosylation of azide 34 and chacotrisyl trichloroacetimidate was performed in the promotion fo HB(C6F5)4(0.1eq) in the BTF/tBuCN/DCM to provide 43β in 70% yield at a ratio of α/β= 1/13.1.43β was subjected to reduction of azide with TMSI followed by removal of the protecting group to furnish solamargine in the yield of 43% through a total of 9 step reactions. On the basis of achieving solamargine, we replaced L-rhamnosyl unit on chacotriosyl moiety with D-rhamnose, L-mannose, D-mannose and synthesized solamargine analogues 31,32, and 33. This work is important to elucidate structure-activity relationships of solamargine pharmacology.