Design, Synthesis And Bioactivity Evaluation Of Novel Cis-Nitromethylene Neonicotinoid Analogues Containing Polycylic Structure

Neonicotinoids, selectively acting on the insect central nervous system (CNS) as agonists of nicotinic acetylcholine receptors (nAChRs), are potent broad-spectrum insecticides that possess contact, stomach and systemic activity. As a result of novel mode of action, no cross resistance with other traditional insecticides and competitive safety profile, neonicotinoids have been globally an integral component in numerous pest and integrated pest management strategies. Based on the main structure of neonicotinoid, four series of new neonicotinoid compounds were designed and synthesized in this dissertation. Furthermore, the biological activities of all target compounds were evaluated. The results provided some compounds with good insecticidal activities as well as reference for further modification.1. A series of new Paichongding derivatives containing fluorine were synthesized by the introduction of fluoroalkyl into two active site of lead compound Paichongding. Among these compounds, A1-A4 showed high insecticidal activities against black bean aphid (Aphis medicaginis), armyworm (Mythimna separata) and brown planthopper (Nilaparvata lugens), it was worth noting that the LC50 of compound A3 against black bean aphid and brown planthopper were 0.4421 and 0.5593 mg L-1, respectively, which were much better than Paichongding.2. The research of neonicotinoids containing hexahydroimidazopyridine:a series of new neonicotinoid compounds were synthesized through the replacement of phenyl by different aromatic heterocycle combining with the introduction of spiro structure. The bioassays indicated that all of the target compounds showed excellent insecticidal activities against brown planthopper (100% mortality) when the concertration was 500 mg L-1. Particularly, compounds B1、B2-1、B3-1、B4-2 and B5-1 kept the excellent bioactivities (more than 95% mortality) at 4 mg L-1. On the other hand, some target compounds also showed moderate insecticidal activities against black bean aphid (more than 80% mortality) and armyworm (more than 60% mortality) at 500 mg L-3. Two concise methods for synthesis of regioisomeric isobenzofuranone spiro (heterocyclic fused pyrrolone) were developed, and the rational formation mechanisms for two compounds were proposed on the comparison of intermediates and products. The remarkable features of two approaches included mild and convenient reaction conditions, a broad substrate scope and moderate to excellent yields. According to two methods, a series of novel neonicotinoids were synthesized and bioassay of target compounds expounded that compounds Cl-a, C3-a and C3-b exhibited high insecticidal activities against brown planthopper with 80-95% mortality at a concentration of 4 mg L-1.4. In view of the reactive diversity of acyclic neonicotinoids, a series of novel acyclic compounds were synthesized through incorporation of isoindolinones to nitenpyram. The preliminary bioassays indicated that the mortality of most target compounds against brown planthopper were 100% at 500 mg L-1. Furthermore, compounds D1 and D2 still maintained 50% and 70% mortality when the concentration was decreased to 4 mg L-1.