Study On Design, Synthesis And Activity Of Natural Active Product β - Hederin Derivatives

Pentacyclic triterpenoid saponins are important compounds of natural saponins, which exist in many plants. Many studies show that pentacyclic triterpenoid saponins present a broad range of promising pharmacological and biological activities, such as anti-tumor, antiviral, anti-inflammatory and immune regulatory function. However, their lower contents in plants and the tedious isolation and purification procedure turn out to be a great obstacle for further pharmacological study. Reseachers in organic synthesis of triterpenoid saponins have made favorable progresses in protecting group manipulation strategy and glycosylation, which will benefit the further synthesis of saponins. However, a few studies on structure activity relationships and mechanisms of active saponins are reported.Oleanane type saponin is one type of pentacyclic triterpenoid saponins. In this dissertation, biological activity and progress in synthesis of oleanane saponins are briefly reviewed. It was reported in literatures that both a-hederin and P-hederin, show excellent inhibitory activity against many tumor cells; and their unique disaccharides, a-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside at 3-OH position, may play an important role in the antitumor activity of this type of saponins.Our lab has done the total synthesis ofβ-hederin and its derivatives hederacolchiside A1 (HE-A1), both of which show excellent inhibitory activity against many tumor cells. On the basis of our former work, we designed and synthesizedβ-hederin derivatives for structural modification of 28-COOH and 4’-OH. Starting from oleanolic acid, two 28-glycosides, four 28-esters, nine 28-amides and six 4’-glycosides were synthesized by sequential glycosylation and Schmidt method. They are all confirmed by MS and NMR. Preliminary pharmacological study showed that most of the synthetic derivatives presented some certain of tumor cytotoxity, especially for 28-amides LWX-7, LWX-lland LWX-12 with the values of IC509.0±1.12μM, 4.74±0.87μM and 8.8±0.98μM against Hela cell line. Futher study on those derivatives will be suggested.