The Structural Derivatization And Bioactivity Evaluation Of Novel Neonicotinoids

The stability of pesticide plays a significant role in pesticide development and commercialization. The problems of resistance, cross-resistance and bee toxicity have attracted more attention as a result of huge and frequent use of neonicotinoids. And the poor photostability and water stability of the nitromethylene neonicotinoids reported by our group affect their further practical use. In this thesis, structure modifications of neonicotinoids were introduced to seek high activity and good stability compounds based on previous work. Also, the chloropyridine pharmacophore was changed to improve the resistance problem and the toxicity to honeybee in the research.1) By introduction of phenyl substituted furan groups to a high activity and low stability structure from our previous work based on π-π enhanced conjugation model. It was found that enhanced conjugation was beneficial to increase the bioactivity and stability. Therefore, a series of novel conjugated neonicotinoids were designed and synthesized. Further studies showed that these compounds exhibited good insecticidal activities and better stabilities.2) Chain-opening neonicotinoids have a broader insecticidal spectrum and unique repellent effects. Therefore, acyclic neonicotinoids with benzofuran groups were designed and synthesized. Most compounds presented good activities against brown planthopper (Nilaparvata lugens) under4ppm concentration. And these compounds also showed better stability in water and under the light irritation than the control.3) Fluoroalkyl was introduced to substitute the pyridine ring of oxabridged compounds and azo-compounds. The preliminary bioassay were determined and fluorine butyl substituted oxabridged compound showed expected activity and no toxicity to honeybee. Seven-membered oxabridged compounds with anilineacyl groups was also synthesized, and they showed moderate insecticidal activities against lepidoptera. The honeybee toxicity test exhibited that the fluoroalkyl compounds had no toxicity to honeybee meanwhile keeping the good bioactivity, the anilineacyl compounds also showd no toxicity.4) Chlorine atom of the chloropyridine ring of imidacloprid and cycloxapride was replaced with other substituents and their insecticidal activities against susceptible strain and resistant strain brown planthopper (Nilaparvala lugens) were evaluated. Discrepant results of activities of imidacloprid and cycloxaprid analogues against brown planthopper were observed. For the imidacloprid-modificaiton series, chlorine atom was replaed by hydrogen atom, the activity of compounds increased with the increasing of cross-resisitance to imidacloprid; while for cycloxaprid-modification series, chlorine atom was replaced by fluorine atom, the bioactivity increased significantly and the cross-resisitance decreased. The imidacloprid-modification series showed a lower toxicity to honeybee.