Design,Synthesis,and Insecticidal Activities Of 4-Propargyloxy Benzenesulfonamide Derivatives

Agricultural production can’t be separated from the use of pesticides,but in recent years with the extensive use of pesticides,environmental pollution,food safety and pest resistance have become more and more serious.Therefore,it is of great significance to create new efficient,safe and green pesticides.A series of dihydroagarofuran compounds with insecticidal activity were isolated from Celastrus angulatus Maxim.Further experiments showed that Celangulin V was the main insecticidal component.The new target,V-ATPase of Mythimna separata was found by using Celangulin V as a probe.After homology modeling,drug virtual screening and activity screening of the V-ATPase H subunit of M.separata,two active lead compounds were found.A class of insecticidal benzenesulfonamide containing propargyl group was obtained by structure optimization and activity detection of the lead compound.In this study,a series of new benzenesulfonamide were designed and synthesized by the substitution of different substituents in benzene ring and sulfonamide to improve their insecticidal activity.The main results are as follows:1.It is synthesized from sodium 4-hydroxybenzenesulfonate,2-fluorophenol,2- chlorophenol,2-bromophenol,3-amino-4-hydroxybenzenesulfonic acid,2-methylphenol and3-methylphenol as main raw materials.There are 141 propargyloxy-containing benzenesulfonamide compounds in 7 series of B1,B2,B3,B4,B5,B6 and B7.The chemical structures were identified by nuclear magnetic resonance and X-ray single crystal diffraction,The correct structure of the compound was identified,and 133 of them were new compounds.2.The gastrotoxic activity of 7 series of compounds against insect M.separata were determined by the method of virus-carrying leaf.The results of activity determination showed that B1,B2,B3,B6 and B7 showed good insecticidal activity against M.separata,while B4 showed low bioactivity and B5 showed almost no bioactivity.Among them, compounds B1.5,B1.7,B1.24,B2.5,B2.6,B2.24,and B3.24 have outstanding insecticidal activities,and compound B2.5 has the highest activity with the LC₅₀ value of 0.23 mg/m L.The insecticidal activity is much higher than that of Celangulin V（21.58 mg/m L）,but there is still a big gap from chemical pesticides such as chlorpyrifos（0.036 mg/m L）.3.A CoMFA model with cross-validation coefficient q²of 0.404 and non-cross-validation coefficient r² of 0.919 was constructed,which provided some guidance for the study of structure-activity relationship.Homology modeling and molecular docking showed that compound B2.5 could effectively bind to the H subunit of V-ATPase in the midgut of the third instar larvae of M.separata.These studies provides a certain guiding significance for the structural optimization of such insecticidal active benzenesulfonamide compounds,and also provides an experimental theoretical basis for the research and development of new potential insecticides.