Structural Derivatization And Bioactivities Study Of Neonicotinoids

Acting on insect nicotinic acetylcholine receptors (nAChRs), neonicotinoids have attracted worldwide attention by virtue of novel modes of action, no cross-resistance with conventional insecticides, broad insecticidal spectra, excellent root uptake properties, contact and stomach toxicity, low mammalian toxicity and environmental friendly property. Seven commercial products were introduced to market during the past 30 years, which shared 20% of the crop protection industry. However, significant increases in resistance and cross-resistance were observed in a range of species after frequent field applications. Based above, series of acyclic and cyclic neonicotinoids derivatives had been designed in this thesis to seek high active compounds, the structure activity relationships had also been studied for further research.1) Pharmaceutical active 1,4-dihydropyridine fragment was introduced to the acyclic neonicotinoids. The insecticidal and anti-cancer assay indicated that synthesized compounds showed good activities against cowpea aphids(Aphis Craccivora Koch), armyworm (Pseudaletia Separate Walker) and brown planthopper (Nilaparvala lugens(Stal)), and certain activities to five tumor cells (Hela, HCT116, A549, K562 and MCF-7).2) Acyclic compounds with N-aza-1,3-diene structure were designed and synthesized. The observed LC50 value against aphids was below 30 ppm, while some compounds showed certain herbicidal acticvities. It indicated that the ring opening had a great impact on the activities.3) Tetrahydropyridine was applied to modify the unstable active intermediates by aza-Diels-Alder Reaction (ADAR). The use of common ADAR is limited due to the need for catalysis and low yield, while our particular reaction was easy to proceed with high yield under no catalyst, the reaction conditions were optimized as well. Targeted compounds were endowed with excellent insecticidal activities against cowpea aphids, some of those rivaled imidacloprid. Meanwhile, photo-stability and water stability study indicated the improvement of target compound against the unstable intermediate.4) The five segments of ADAR products were modified by multi-component reactions (MCRs) to afford a series of compounds and evaluated their insecticidal activities. Bioassay indicated three of the five segments were the key factors response for activity difference. Then one product was chirally separated to get four optically pure isomers and test their insecticidal activities. Afterwards, two kinds of regression equation were obtained using genetic function approximation (GFA) as QSAR models.