Study On Synthesis Of Several Saponin Derivatives And Biological Activities And Total Synthesis Of The Natural Product Betavulgaroside Ⅲ

Saponins are complex glycosides of steroids and triterpenes,with significant pharmacological activities,and widely distributed in higher plants.Specially,the biologically active ingredients of many Chinese herbs are the compounds of the saponins.However,it is difficulty by isolating and distilling for large acquisition of pure saponins from natural sources.So the mechanical studies of the bioactivities of saponins can't be favourably developed because of that.Specially,the mechanical studies based on molecular level and animal level have no advancement.Currently,in order to search new active moleculars,the common methods of constructing the compound library have been adopted.Thus,it is not only extensive studies of kinds of bioactivities,but also even more establishing some structure-activity relationship based on a lot of testing dates,and establishing the basic for Pharmaprojects,too.1.Synthesis of the Typical Glucuronide-Containing Saponin and Study on Structure-Activity RelationshipGlucuronopyranosyl oleanoside and their derivatives belong to triterpene saponin, with kinds of bioactivities.For study on the structure-activity relationship,this paper designed and developed high-performance synthesis route,and established a compound library.Then this thesis made some research on antineoplastic activities, and came to a rude conclusion:the compound 3-O-β-D-glucuronopyranosyl oleanoside is the active center of the correlative molecular;if the 28-COOH of the oleanolic triterpene is replaced,the bioactivity fall;if the carboxylic acid of the glucuronopyranoside is protected by methyl ester,the bioactivity may fall,too;but if the 4-OH of glucuronopyranoside is replaced by other sugars,the bioactivity has little change.All upon is in according on the report that the oleanolic acid 3-O-monodesmoside is necessary for the bioactivity.2.Synthesis of Dioscin Derivatives and Study on Biological ActivitiesDioscin,a typical diosgenyl saponin,has kinds of bioactivities such as cardiovascular,cytotoxic and antifungal activities.For farther study on the mechanism of the bioactivity and searching their intracellular functionary targets,we synthesized a series of diosgenyl saponin derivatives and made some bioactivity tests. This paper succeeds at searching out the molecular reconstructive site in order to research the mechanism of the bioactivity by appending the biotin or fluorophore.On the basis of early work,this paper reconstructed the 6-OH of glucose and the 4-OH of one rhamnose because of their weak influence on bioactivity and made some tests of the activities of hemolysis and antitumour.From the gained datas,this paper considered the 4-OH of the rhamnose as the best appropriate site for appending the fluorophore,and ulteriorly proved the active mechanisms between hemolysis and antitumour are different for these molecules.3.Total Synthesis of the Natural Product BetavulgarosideⅢwith acidic acetal substituentsSince 1994,a class of saponins with novel acidic acetal-type and acidic dioxolane-type substituents had been isolated from the root of Achyranthes fauriei and Beta Vulgaris by different work-groups,respectively.This structure type was firstly discovered among natural products.It was reported that these saponins have kinds of bioactivities,especially some of them have highly anti-inflammatory activity. For farther study on their bioactivities and the synthesis method of these kinds of saponins,BetavulgarosideⅢwas chosen as our target molecule.This thesis explored the synthetic route toward stereo-isomer of BetavulgarosideⅢ,and successfully synthesized the stereo-isomer by the tactic of linear strategies glycosylation and the tactic of convergent block synthesis,respectively.And adopting the tactic of convergent block synthesis,this paper successfully synthesized the compound BetavulgarosideⅢ.Finally,adopting the tactic of convergent block synthesis as the common method of these molecules,we explored the synthetic conditions to the key block of other molecules,and established the basic for the class of the molecules.