Design, Synthesis And Insecticidal Activity Studies Of Novel Podophyllotoxin And Camptothecin Amidines Derivatives

This thesis described herein involves the two main parts as follow.Part Ⅰ:Design, Synthesis and insecticidal activity Studies of novel Podophyllotoxin Amidines DerivativesPodophyllotoxin, a naturally occurring aryltetralin lignan, besides its use as the molecular precursor for the development of potent antineoplastic drugs and antiviral agents, exhibited the promising insecticidal activity.Considering the high toxic residue and resistance of the chemical pesticide, we made full use the region advantage of the northwest, and podophyllotoxin with insecticidal activity was extracted from endemic plant Sinopodophullum hexandrum of Gansu Province. And on this basis, the structure of podophyllotoxin was modified. Podophyllotoxin amidines derivants were synthetized by the Copper-catalyzed multicomponent reactions according to the physicochemical property of amidines. The antifeedant activity and insecticidal activity against Brontispa longissima were further researched. The results showed that activities of most derivants were higher than podophyllotoxin and toosendanin. Mechanism of inhibiting the tubulin polymerization were preliminary explaned by molecular docking test and activity determination of tubulin in vitro. The prospects of some derivants are cheerful and can be exploited as new Plant source pesticide.Part Ⅱ:Design, Synthesis and insecticidal activity Studies of novel Camptothecin Amidines DerivativesCamptothecin and its derivatives possess high cytotoxicity as inhibitor of topoisomerasel and can be used to cure various kinds of tumors such as cancer of the liver、osteocarcinoma、bladder carcinoma and leukocythemia.13kinds of derivants were utilized in clinical. At the same time camptothecin possesses insecticide activity.lt is a potential pesticide with high effect, low toxity and good compatibility with environment as a chemical apholate.Considering the synthesis and bioactivity of Podophyllotoxin amidine, Camptothecin amidine were designed and synthesised by Copper catalyzed multicomponent reaction with Amino acid methyl esters, and the biological activity of Camptothecin Amidine derivatives to Brontispa longissima (Gestro) were preliminary tested. The results showed that activities of some derivants were higher than Camptothecin, which was beneficial to increasing the bioactivities of Camptothecin.