Design,Synthesis And Insecticidal Activity Of Novel Insecticides Targeting Mitochondrial Complex Ⅱ

The mitochondrial oxidative phosphorylation electron transport chain complex Ⅱ,which called succinate dehydrogenase(SDH)plays an important role in cell aerobic respiration and the tricarboxylic acid cycle.It is a significant target for the pharmacy and agrochemical industry.In recent years,fungicides targeting mitochondrial complex Ⅱhave been favored by researchers due to their high efficiency and broad-spectrum fungicide activity,but insecticides that target complex Ⅱ have been rarely reported.The known complex Ⅱ commercialization Thiapronil is the eariest insecticide.On the basis of its novel acrylonitrile structure,Researchers made a large modification and then developed the coumpounds Cyflumetofen,Cyenopyrofen and Pyflubumide with good killing mites activity.Except for thiapronil,others have no activity against insect,so it is vital to develop favorable insecticidal compounds with novel structures and unique mechanism of action targeting compound Ⅱ.In this paper,we chose commercial Cyflumetofen as the lead compound,designed and synthesized a series of new skeleton compounds containing ethylene oxide and propionitrile structure by uniting the structure of the metabolic product OH-form of commercial acaricide Cyflumetofen and Cyenopyrofen.All compounds have certain insecticidal activity against the armyworm.Concrete research contents are as follows:1、The structure and function of mitochondrial complex Ⅱ are systematically summarized.and their history,research progress and synthesis methods of commercial mitochondrial complex Ⅱ are introduced.2、64 target compounds of two major categories were designed and synthesized,and all the compounds were characterized by 1H NMR,13C NMR and HRMS,and some of their structures were confirmed by SC-XRD.3、The test data of insecticidal activity of all synthetic target compounds were provided by the Bioassay Center of Zhejiang Research Institute of Chemical Industry.The experiment results showed that most of the compounds had a favorable insecticidal effect on the armyworm at a concentration of 500 mg/L.Some of the compounds still had a certain insecticidal activity against the armyworm at reduced concentration.I-8d-10(Y17537)has 80%lethal rate at a concentration of 20 mg/L against armyworm.The results showed that the dipheny ether structure fragment with a wide range of biological activities had excellent activity against armyworm providing with important reference value for the further modification of the compounds.At the same time,some compounds showed a certain lethality of AphiscraccivoraKoch at a concentration of 500 mg/L.This article summarizes the preliminary structure-activity relationships of the synthesized ethylene oxide propanenitriles,providing a reference for the design of novel mitochondrial complex Ⅱ insecticidal inhibitors.