Design,Synthesis And Insecticidal Activity Of 4-Acetonitrileoxy-Benzenesulfonamide And Amino Acid-Substituted 4-Propargyloxybenzenesulfonamide Derivatives

Pests are one of the most important factors affecting agricultural production,because of its high speed and difficulty in prevention and control,pests have always been a threat to crops from sowing to harvesting.So far,chemical pesticide is still the most effective measure to control plant pests.Nevertheless,high frequency and high dose use of insecticide agents have led to an increase in pest resistance and increased pesticide residues,therefore,it is particularly important to discover pesticides with novel mechanisms of action to protect crop production and maintain food security.Our research group using the V-ATPase H subunit as a template,two benzenesulfonamides（2-（4-chloro-5-（N-（4-ethoxyphenyl）sulfamoyl）-2methylphenoxy）acetamide,2-（4-chloro-2-methyl-5-（N-（p-tolyl）sulfamoyl）phenoxy）acetamide）with insecticidal activity were obtained by homology modeling and computer-aided drug design,experiments showed that two compounds had good stomach toxicity to larvae and symptoms of the larvae being poisoned by them were similar to those of Celangulin V,futher study showed that 4-propargyloxybenzenesulfonamide exhibited good poisoning effect to larvae,especially,N-butyl-4-propargyloxybenzenesulfonamide showed excellent insecticidal activity with the LC₅₀of 1.32 mg/m L.This topic was based on the secondary lead optimization of 4-propargyloxybenzenesulfonylbutylamine,129 novel benzenesulfonamide derivatives were designed and synthesized by replacing propargyloxy with acetonitrileoxy and using different amino acids as amino substituent,the insecticidal activity of the target compounds was evaluated by leaf loading method and the structure-activity relationship was studied preliminarily.The main results are as follows:1.Synthesis of 4-acetonitrileoxybenzenesulfonamide derivatives（A）:sulfonamide group was retained,4-propargyloxy was replaced by 4-acetonitrileoxy,fluorine,chlorine and methyl were introduced on the benzene ring,60 novel 4-acetonitrile oxybenzene sulfonamide derivatives were designed and synthesized,structures were characterized and confirmed mainly by NMR and X-ray single crystal diffraction.All of them are new compounds.2.Amino acid-substituted synthesis of 4-propargyloxybenzenesulfonamide derivatives（D,E）:4-propargyloxy was retained and different amino acids were introduced as amine sources,69 novel 4-propargyloxybenzene sulfonamide derivatives were designed and synthesized with amino acid substituted,structures were characterized and confirmed mainly by NMR.All of them are new compounds.3.Insecticidal activity evaluation and structure-activity relationship:Insecticidal activity of title compounds was evaluated by leaf loading method against the 3^thinstar larvae of M.Separata.（1）The results of insecticidal activity of 4-acetonitrileoxybenzenesulfonamide derivatives indicated that the activity of these compounds was generally lower and the introduction of cyano group on benzenesulfonamides was not beneficial to the activity of the compound,in addition,the introduction of CH₃on the benzene ring is more active than Cl and F.（2）The results of insecticidal activity of amino acid-substituted 4-propargyloxybenzenesulfonamide derivatives showed that the number of carbon atoms in amino acids had a significant effect on the activity of these compounds,in particular,compounds with long-chain（4 or 5 carbon atoms）exhibited excellent insecticidal activity,the LC₅₀of D16 was 2.38 mg/m L,the activity improved by 14 times compared to Celangulin V（34.48 mg/m L）.At the same time,we found that the difference in amino acid configurations had a significant effect on the insecticidal activity of these compounds.L-type amino acid derivatives had higher activity than D-type amino acid derivatives,the LC₅₀of D16 was 2.38 mg/m L,lower than that of D49（10.15 mg/m L）;The above results provided theoretical and experimental basis for the discovery of novel insecticidal active compounds.