Synthesis And Biological Activity Evaluation Of Novel Neonicotinoid Compounds Through The Active Ligand-based Design

The goals of this research were the structural developments of neonicotinoid compounds through the chemical derivatizations. Three series of neonicotinoid compounds had been synthesized based on the active ligand-based design in this thesis. The bioactivities of the target compounds were evaluated, and structure-activity relationships were also studied. The crystal structure of the supramolecular assembly of Pymetrozine in methanol and its hydrochloride salts in water had been examined for better understanding the structure and behavior of functional molecules in biological systems.1) A series of novel neonicotinoids with the O,O-diethylphosphonothioate structure were designed and synthesized based on the heterocyclic modification. The biological activity evaluation showed that these compounds didn’t exhibit significant insecticidal activity against cowpea aphids (A. craccivora). Molecular docking results of lead compound and synthesized compound with the AChBP implied that the synthesized compound couldn’t bind with the AChBP very well because of the steric configuration difference.2) A series of novel neonicotinoids with cis-configuration were designed and synthesized through Nenitzescu reactions. The biological activity evaluation showed that these compounds didn’t exhibit significant insecticidal activity against cowpea aphids (A. craccivora). The calculated Log P of the designed compound was lower than that of the lead compound, which implied that cuticular penetration of the designed molecule is difficult.3) A novel class of neonicotinoids, in which the common nitromethylene pharmacophore was substituted by electrophilic thiocyanogen reagents, were designed and synthesized. Most of the compounds exhibited excellent insecticidal activities against cowpea aphids (A. craccivora), which implied that reaction of nitromethylene with the electrophilic system to obtain novel neonicotinoids analogues with high activities was feasible. It was observed that compounds with NO2substituent demonstrated better activities than that with CN substituent. Generally, the imidazolidine substituent appears to be the important factor for insecticidal activities. Moreover, the cyclic addition of SCN substituent with the imidazolidine ring is unfavorable for high activities from the data analysis.4) The crystals of functionalized pymetrozine hydrochloride salts in water and neutral pymetrozine in methanol have been obtained. Our results provide a new insight and an improved understanding of the three-dimensional structural aspects of hydrogen bonded liquids with important implications in the structure and behavior of functional molecules in biological systems.