九节龙皂苷ⅰ衍生物合成及活性筛选-synthesis and activity screening of jiujielong saponin ⅰ derivatives.docx

III IV Abstract Pentacyclic triterpene saponins and their sapogenins, naturally occuring in a large variety of plants, have attracted much attention due to their multi-faceted biological activities including significant antitcancer and antiviral properties. Ardipusilloside Ⅰ, a pentacyclic triterpenoid saponin isolated from Ardisia pusilla A. DC, has been shown to have inhibitory effect on the growth of a variety of cancer cells and immunoregulatory effect on human immune responses. Cylamiretin A is the primary sapoginin of Ardipusilloside Ⅰand Cyclamiretin D is the secondary sapoginin. So far no research has been reported on the anticancer activities of Cylamiretin A and Cyclamiretin D. Chemical modification of Ardipusilloside Ⅰand its sapoginins and biological screening of their derivatives are of great significance in clarifying their structure-activity relationship and developing better saponin-type anticancer drugs. This work mainly consists of the following four parts:  Six Ardipusilloside Ⅰderivatives were synthesized by oxidation or  reduction of the C-30 formyl group of the saponin, or condensation of the C-30 formyl group with various amino compounds such as thiosemicarbazide, hydroxysemicarbazide, and methyl hydrazinecarbdithiolate. Cylamiretin A and Cyclamiretin D were obtained by hydrolysis of Ardipusilloside Ⅰ under various conditions. It has been shown that acid-catalyzed homogeneous hydrolysis of Ardipusilloside Ⅰ mainly gave Cyclamiretin D while biphasic hydrolysis of Ardipusilloside Ⅰmainly gave Cylamiretin A. Five C-3 ester derivatives of Cylamiretin A were obtained by treatment of Cylamiretin A with various organic acid or acid anhydride. Thirteen Cyclamiretin D derivatives were prepared by oxidation or esterification of Cyclamiretin D, or condensation of Cyclamiretin D with animo compounds such as thiosemicarbazide, 1-aminopiperidine and methyl hydrazinecarbdithiolate. Anticancer anctivities of Ardipusilloside Ⅰderivative