Study On The Synthesis And Acaricidal Activity Of Silicon-Containing-β-Ketonitrile Derivatives

Agricultural pest mites are a group of biological populations with strong adaptability,fast reproduction speed,and great difficulty in control.As an important exporter of grain and cotton,China has been exposed to mites all year round.At present,acaricides are the main means of controlling mites.In recent years,the irrational use of acaricides has led to increasing drug resistance of agricultural mites.There are few varieties of acaricide that have been marketed and have severe cross resistance,so it is urgent to develop new acaricide candidates to meet the current production needs of crops.β-Ketonitriles and derivatives acaricides stand out among many acaricides due to their novel chemical structure and unique mechanism of action.They are also characterized by safety to non-target living things,environmental friendliness,and no cross resistance to existing insecticides and acaricides.They are suitable for the comprehensive management of various pests and mites,and have become a hot research field of acaricides.In the past ten years,there are only 3 species ofβ-ketonitriles and derivatives acaricides,which still have great development potential.Silicon is a member of the same group as carbon.Although they have similarities in atomic structure and chemical properties,compared to carbon,silicon has a smaller electronegativity,a relatively larger atomic radius,and has empty d orbitals,which can affect the physical and chemical properties of silicon-containing compounds.As an important means of structural optimization,carbon-silicon exchange bioelectronic isosteric strategy is mainly used to expand the chemical space of drug molecules,enhance the affinity between drugs and target proteins,and improve the lipid solubility of drugs.Based on this strategy,several marketed products have been successfully developed,such as the fungicide silthiazolamide and the insecticide flusilrin.However,this strategy has rarely been reported in the development of SDH targeted acaricides.Hence,this article reports the discovery of a novel SDH targeted acaricide lead structure using a carbon silicon exchange bioelectronic isosteric strategy.The specific research content is as follows:1)Based on carbon-silicon exchange bioelectronic isosteric strategy,50 silicon-containingβ-ketonitrile derivatives were designed and synthesized,and the structures of all synthesized target compounds were confirmed by ¹H NMR ¹³C NMR and HRMS.2)Through screening for acaricidal activity,a number of lead compounds 7-6,9a-6,9a-8,9c-13,and 9c-14 were found.Under six concentration gradients（10,5,2.5,1.25,0.625,and 0.3125 mg/L）,compound 7-6 had 100,100,97,54,32,and 22%control effects against tetranychus cinnabarinus indoors,respectively,comparable to the positive control of Cyetpyrafen（100,100,100,100,76,and 32%）,and superior to Cyenopyrafen（100,100,51,36,and 11%）;Under the same concentration gradient,the control effectiveness of 9a-8 against tetranychus cinnabarinus in the indoor environment was100%,100%,95%,81%,55%,and 38%,respectively,which was significantly better than Cyenopyrafen and slightly better than Cyetpyrafen.In addition,under four concentration gradients（100,10,1,and 0.5 mg/L）,compound 7-6 had a control efficacy of 100,100,100,and 71%against indoor tetranychus urticae,respectively,which was comparable to that of Cyetpyrafen（100,100,94,and 79%）;Under the same concentration gradient,compound 9a-8 had a control effect of 100,100,100,and 94%against indoor tetranychus urticae,respectively,significantly superior to Cyetpyrafen,and had better rapidity.In summary,based on the carbon-silicon exchange bioelectronic isosteric strategy,we have successfully discovered lead compounds for novel SDH targeted acaricides with novel structures,excellent acaricidal activity,and indoor control effects comparable to that of Cyetpyrafen providing a meaningful reference for the application of carbon-silicon exchange bioelectronic isosteric strategy in the development of new insecticides and acaricides.