The Design, Synthesis And Insecticidal Activity Of A Novel Pyridyl-containing Butenolide Derivative

Flupyradifurone was the first butenolide insecticide discovered by Bayer CropScience in recent years.It has many advantages,such as high activity,no cross-resistance to nicotinamide insecticide,accelerates plant growth,safety to bees,low toxicity,which is a research hotspot of novel insecticides.While,halogen-containing phenyl groups are an important part of pesticides,it can not only increase the biological activity of the lead compound,but also reduce the toxicity of it.Therefore,it was usually used to designed and synthesized novel pesticides,in order to investigate the effect of halogen-containing phenyl groups on the biological activity of the lead compound flupyradifurone and further develop highly effective butenolide insecticides.A series new 4-?N,N-diarylmethylamines?furan-2?5H?-one derivatives were designed and synthesized for the first time by replaced the difluoromethyl group with halogen-containing phenyl groups,and their structures were authenticated by ¹H NMR,¹⁹F NMR,¹³C NMR and HRMS,we also evaluated the insecticidal activity and investigate the preliminary insecticidal mechanism of action.In this paper,the major results were summaried as follows:?1?The potassium methyl malonate,5-?aminomethyl?-2-chloropyridine,different romatic aldehydes as original materials.We synthesized the target compounds 4a-4cc by substitution,cyclization,aldimine condensation,reduction,dehydration and decarboxylation reaction.Their structures were authenticated by ¹H NMR,¹⁹F NMR,¹³C NMR and HRMS.?2?The insecticidal activity of the target compounds 4a-4cc were evaluated by spraying method and contacting method,the result indicated that most title compounds showed excellent insecticidal activity against Aphis craccivora and Meloidogyne incognita at the concentration of 500?g/mL and 100?g/mL,especially compounds 4i,4m,4s,4u,4z,4cc have 100%motality against Aphis craccivora.The insecticidal activity was higher than the commercial pesticide pymetrozine?89.31%?and similar to commercial insecticide flupyradifurone;The LC₅₀ values of compounds 4f,4i,4s,4t and 4cc against Aphis craccivora were 4.96,4.34,5.31,5.44 and 1.72?g/mL respectively,which were better than the commercial insecticide pymetrozine(LC₅₀=6.86?g/mL);The target compounds 4c,4k,4m,4q,4z and 4aa have the motality of82.89%,85.40%,85.76%,82.60%,81.95%and 82.40%respectively,at the concentration of 100?g/mL,which were better than the commercial insecticide flupyradifurone?49.97%?,however,they exhibited lower nematocidal activity than abamectin.?3?The molecular docking result of 4cc and imidacloprid with the CYP6CM1vQ indicated that their conformational spaces were completely different.The imidacloprid conformational spaces was easy to oxidative metabolism,but 4cc may lacks of oxidative metabolism which induced by CYP6CM1 and absences of metabolic resistance with acetylcholine receptor insecticide imidacloprid.?4?The insecticidal mechanism of high activity compoud 4cc was investigated by label-free quantitative proteomics analysis,the result indicated that 4cc have a great impact on energy metabolism,immunologic process,neuronal signal transduction process and neuronal signal transduction of Aphis craccivora.For example,4cc can decrease the ability of oxidative metabolism,which was consistent with the result of molecular docking;We can known that 4cc may be a potential acetylcholine receptor insecticide by pathway analysis,which can act on the nAChR and regulate ion channels,then control pests neural signaling and activities.