Synthesis And Biological Evaluation Of Natural Steroidal Saponins And Their Derivatives

Steroidal saponin is a kind of compounds which were distributed widely in nature.As an important nature product, it has been found in many terrestrial plants (Ginseng, Garlic, Anemarrhena etc.) and marine organisms (Star fish, Sea weed etc.). Steroidal saponin is composed of the sugar unitand a nonpolar aglycon, in which the sugar unit may be a monosaccharide or oligosaccharide chain having2to5monosaccharides. It has been reported that the effective compositions of many Chinese medicines are Steroidal saponins. Steroidal saponin is associated with many pharmacological effects, such as antitumor, antibacterial, spasmolysis, hpyerglycemic, antiatheroscloresis, anti-platelet aggregation, anti-flammatory activities. Hence, it is significative to focus on steroidal saponins.The content of steroidal saponins is very poor in natural plants and organism. There is a great lose during the extraction and separation by traditional extraction way, which have been hindered to further investigate their pharmacological effects, side effects, structure-activity relationship (SAR). Compared to the traditional extraction fasion, the chemical synthesis has more advantage such as high yeild, high output and high repeatability, and it has been becoming a important and effect way to gain steroidal saponins and its derivatives.In this thesis, several natrural steroidal saponins having potential antitomor activies were chemically synthesized, and their structural derivatives were also designed and synthesied for further SAR study. The antitumor activities of the synthetic saponins were evaluated in vitro. Three chapters are mainly included in this thesis:The latest research process of pharmacological activities of steroidal saponins was reviewed in chapter1. The recent process on effects of steroidal saponins were summarized from the following aspects:antitumor effects, antibacterial activities, the effects towards hematologic system and anti-inflammatory action etc.In chapter2, the facile synthesis and biological evaluation of Timosaponin AIII isolated from rhizoma anemarrhenae and its derivatives were investigated. Timosaponin AⅢ(TAⅢ) is a disaccharide saponin isolated from rhizoma anemarrhenae and has been reported to be possessing antitumor, anti-platelet aggregation, hpyerglycemic activities. In order to study the biological activities and structure-activity relationships of TAⅢ and its derivatives, we hernin designed and synthesized TAⅢ and its five structural derivatives including two aglycon and three sugar unit replaced derivatives by one-pot sequential glycosylation strategy. The biological activities of the synthetic saponins were assayed, and the results showed that the galactosyl and rhamnosyl derivatives of TAⅢ showed much stronger anti-proliferative activities than that of TAIII. The IC50value of its rhamnosyl derivative towards HeLa cell can be lower to3.3μM, which is worth to further inverstigate its antitumor mechanism.Chapter3described the synthetic methodology on preparation of steroidal saponins from Allium plant and its derivatives. Allium is a kind of plant that distributed widely in the world, and there are about500kinds of Allium plants all over the world and about100kinds in China. This kind of plant has been reported having anti-flammatory, antitumor, antibacterial and other activities. As the basic active ingredient of the Allium plant, steroidal saponin also possesses such biological acticities. Its antitumor activity is one of the most important biological roles which was attracted much attentions. In this chapter, we design six steroidal saponins from Allium and its derivatives bearing tingogenin as aglycon and galactose unit as the sugar chain core. Four steroidal saponins3-6were successfully synthesized, and the attempt to synthesize steroidal saponins1and2were also explored in our study.