Design,Synthesis,and Insecticidal Activities Of Propargyloxy-naphthalene-sulfonamide Derivatives

The development of agriculture is inseparable from pesticides,but repeated use of a large number of pesticides will lead to increased resistance to diseases,pests and weeds in agriculture.Finding new targets or new mechanisms of action of pesticides is of great significance to pest control and crop protection.The previous experiment of the research group found that celangulin V has a good gastric toxicity to the oriental armyworm.A new target V-ATPase H subunit was found using celangulin V as a probe,and benzenesulfonamide compounds were obtained through computer-aided drug design and homology modeling.After the pilot optimization of benzenesulfonamide compounds,it was found that the benzenesulfonamide compounds containing propargyloxy groups had insecticidal activity against the oriental armyworm.Then,a series of compounds were synthesized with the propargyloxy-containing benzenesulfonamide compound as the lead compound,verifying that the propargyloxy group and sulfonamide substituents play a vital role in the insecticidal activity of the lead compound.In order to develop new insecticides and improve the insecticidal activity of these propargyloxysulfonamide compounds,a naphthalene ring was substituted for the benzene ring.A series of propargyloxynaphthalenesulfonamide derivatives were designed and synthesized.The structure of the compound was identified by NMR and other means,and the insecticidal activity of the target compound was determined by the leaf dip method.The main results are as follows:1.With 2-hydroxy-7-naphthalenesulfonic acid,2-hydroxy-6-naphthalenesulfonic acid,4-hydroxy-1-naphthalenesulfonic acid,5-hydroxy-1-naphthalenesulfonic acid,2,3-dihydroxy-6-naphthalenesulfonic acid,6-amino-4-hydroxy-2-naphthalenesulfonic acid,6 different hydroxynaphthalenesulfonic acids as raw materials,through Williamson ether formation reaction,sulfonyl chloride reaction,amine formation reaction to obtain E3,E4,E5,E6,E7,E8,a total of 126 kinds of 6 series containing propargyloxynaphthalene sulfonamide compounds.2.The insecticidal activity of these 126 propargyloxynaphthalenesulfonamide compounds was determined by the virus carrying leaf method.The insecticidal activity test results showed that the E3 series of compounds were inactive,and the E8 series of compounds had generally low activity,while most of the target compounds of E4,E5,E6 and E7 had significant gastric toxicity to the 3rd instar armyworm larvae.Among them,E7.4,E7.11,E7.4,E7.21,E4.3,E4.11,E5.4,E6.4 showed outstanding activity,and the LC₅₀value of E7.4 was0.19 mg/m L,Much lower than the positive control celangulin V（23.5 mg/m L）but higher than the existing insecticide indoxacarb（3.7 mg/L）.3.The structure-activity relationship of the compound was discussed,and the molecular docking of compound E7.4 with the V-ATPase H subunit verified the binding mode of the compound with the target receptor.The results showed that E7.4 had an effect on the V-ATPase H subunit.The base can be combined stably.From a molecular point of view,it has been verified that compounds with propargyloxynaphthalenesulfonamides have insecticidal activity against Mythimna separata,can be used as candidate compounds for new insecticides,and are expected to be further developed as potential insecticide candidate compounds.