The Natural Active Products Of Methyl Protodioscin Derivatives, Synthesis And Biological Activity Study

Furostanol saponins widely distributed in nature possess various important bioactivities, such as antitumor, anti-inflammatory, antibacterial, antivirus, immunoregulation and so on. Therefore, this class of natural product has drawn more and more attention from chemists worldwide. Methyl protodioscin (MPD) is a member of furostanol saponin family which was isolated from the rhizome of Dioscoreaceae a kind of traditional Chinese herb medicine. It had shown significant anticancer activity in vitro with a panel of 60 human cancer cell lines performed in NCI. Based on the encouraging discovery we decided to synthesize a series of derivatives of MPD. They are protodioscin PD1, ethyl protodioscin PD2, andΔ^20,22 neoprotodioscin PD3. Replacing the glucosyl moiety at C₂₆ of Methyl protodioscin with its chacotriose moiety at C3 furnished two novel bisdesmosidic furostanol derivatives DT1 and DT4.Employing the stepwise glycosylation strategy, diosgenin was glycosylated by glucose and rhamnose orderly. Through oxidation and reduction, the newly exposed C₂₆-OH connected with another one equivalent glucose. The furostanol structure was constructed by NaBH₄. As for DT1 and DT4, we also apply the stepwise glycosylation strategy. Finally, we succeeded in synthesizing PD1, PD3, DT1 and DT2 in 11 steps and PD2 in10 steps. The total yields of them are 8.7%, 7.3%, 10.4%, 10.1% and 8.8% respectively. Recrystallization was used to purify intermediates in some early processes which greatly improve the efficiency and the yield.All the target compound and intermediates were identified by ¹H-NMR, ¹³C-NMR and ESI-MS. The melting point and optical rotation of the solid-state materials were measured.