Design, Synthesis, Insecticidal Activity And Mechanism Of Action Of Novel Nitrogen-containing Heterocyclic Pyrido[1,2-a]pyrimidinone Mesoionic Compound

In view of the practical problems of difficult control,heavy resistance and lack of effective control agents of rice planthopper in rice production in China and even Asia.Under the guidance of academician Baoan Song,focusing on the creation and application of high-efficiency rice planthopper control agents,and the research hotspot of mesoionic insecticides.The design,synthesis,insecticidal activity and action mechanism of the new type of pyridino[1,2-a]pyrimidinone mesoionic compounds containing nitrogen heterocycles were carried out.A new high-efficiency rice planthopper control agent Yizuochongmiding with independent intellectual property rights was created.The main research contents of this paper include five aspects as following.1.Fifty pyrido[1,2-a]pyrimidinone mesoionic compounds containing indole and thirty-five pyrido[1,2-a]pyrimidinone mesoionic compounds containing isoxazole were designed and synthesized.The insecticidal activities of the target compounds were tested using a spraying method.The LC₅₀values of compound A7 aganist bean aphid（Aphis craccivora）and white backed planthopper（Sogatella furcifera）were0.85 and 0.86μg/m L,respectively.The insecticidal activity aganist A.craccivora was better than that of the control agent triflumezopyrim（3.67μg/m L）.The LC₅₀ value of compound B2 aganist S.furcifera was 0.22μg/m L,which was equivalent to triflumezopyrim（0.21μg/m L）.Compound B2 was named"Yizuochongmiding"by the National Technical Committee for pesticide standardization.2.The laboratory virulence of Yizuochongmiding aganist brown planthopper（Nilaparvata lugens）sensitive strain and brown planthopper resistant strain was determined.The LC₅₀of compound Yizuochongmiding aganist N.lugens indoor sensitive strain,nitenpyram resistant strain,clothianidin resistant strain,sulfoxaflor resistant strain,dinotefuran resistant strain and Xinyang field population were 0.08,3.78,1.20,1.22,0.21,and 0.38μg/m L,respectively,which showed no cross resistance,and had excellent control effect on the field population of N.lugens.At the same time,the efficacy evaluation of candidate drug against field planthopper was carried out in Jurong and Huaian（Jiangsu）,Changsha（Hunan）and Wuxue（Hubei）.The results showed that the candidate drug could effectively control rice planthopper and showed excellent rapidity and retention.The relevant patent was exclusively authorized to Guangxi Tianyuan Biochemical Co.,Ltd.for industrial development with 16 million yuan.3.The laboratory virulence of Yizuochongmiding aganist the 3rd instar of N.lugens was tested by root immersion method and topical application method.The LC₅₀ of root immersion method was 0.36μg/m L.The LD₅₀ of topical application method was 1.848×10^-3 ng/head.The results showed that Yizuochongmiding had internal suction and contact toxicity.4.The toxicity of Yizuochongmiding aganist bees was carried out.The LD₅₀ of contact toxicity to bees was>28μg/bee,and oral toxicity of bees was>11μg/bee.The results showed that Yizuochongmiding had low toxicity to bees,overcoming the bee venom problem of triflumezopyrim.5.The nicotinic acetylcholine receptor was identified as the target of Yizuochongmiding by enzymatic activity test,proteomics and molecular docking.By measuring the resistance of different n ACh Rs mutant Drosophila strains to isozosin,it showed thatβ2 subunit andβ3 subunit might be a potential target of Yizuochongmiding.