Synthesis Of The Anticancer Agent Methyl Protodioscin And Fesogenyl Saponins

Saponins exist widely in the plants,which have various physiological activities and own medicinal value and exploitation potential.With the accumulation of research results of saponins,the research focus on their structures converted from the aglycone deeply into both the aglycone and the sugar chains.However,due to the low content of saponins in the plants, and the complexity work of separation and purification,the pharmacological studies were restricted to some extent.Chemical synthesis could prepare amount of various saponins, therefore more and more attention were paid to it.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.This compound was firstly synthesized by Dr.Qian-li Wang in 2003, however,it could not illustrate the formation of theβconfiguration of the glycoside bond in the establishment of C₃ sugar chain,which was a theoretical defect.To resolve this problem, we designed two routes to resynthesize MPD.The first route was based on Wang's route,in which manipulation of protective groups were introduced in the establishment of C₃ sugar chain,and theβglycoside bond was formed directionally by utilization of participatory effect of protective groups.This route was given up for it failed to realize the selective deprotection. The second route firstly studied the tautomerization of the key intermediate from spirostane to cholestane 3-O-substituted kryptogenin,then formed a direct access used Zn/KI/HOAc reduction,which supplied a better synthetic method of MPD and other furostanol saponins. 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 the reduction with NaBH₄.Finally MPD was obtained in 9 steps with a total yield of 1.3%.Fesogenin was a compound synthesized in the steroidal chemistry,of which the saponins had not been reported.Using fesogenin and five types of sugar donors,we prepared 23 novel fesogenyl glycosides(41a-41w) via total 10 random glycosylation procedures.The screening of their pharmacological activity is in the progress.