Design,Synthesis And Evaluation Of Novel Polyfluoropyrethroids As Anti-mosquito Agents

Mosquito is one of the most widely distributed and deadliest creatures in the world,which generally carried a variety of viruses and spread to human or other creatures during the process of biting.Among them,Aedes albopictus is the main vector of more than 20 disease,such as dengue fever,dengue hemorrhagic fever and Japanese encephalitis,which posing a serious threat to human health.At present,the main measures of mosquito prevention and control are environmental control and comprehensive use of chemical pesticides.During the chemical prevention and control,pyrethroid insecticides have been widely used for a long time because of their high efficiency,low toxicity and low residue advantages,meanwhile the problem of mosquito resistance has been increasingly emerging,which has been attracted more attention.In order to develop novel and effective pesticide to alleviate the public health problems of mosquito resistance,a series of polyfluorinated pyrethroid was designed and synthesized in this study.54 novel polyfluorinated pyrethroids were synthesized by etherification,reduction,cyanation and esterification,in which tetrafluorophenyl group was introduced in the start material of deltamethrin.All of the target compounds’structure was characterized by ¹H HMR,¹³C HMR and high-resolution mass spectrometry（HRMS）.In this study,the anti-mosquito activity of susceptible and resistant Aedes albopictus adult was tested by CDC Bottle Bioassay that was recommended by the Centers for Disease Control and Prevention of the United States.The results of anti-mosquito activity for susceptible adult mosquito showed that 14 compounds showed potential anti-mosquito activity,and their LC₅₀ranged from 0.45±0.05 to 2.10±0.47 mg/L,which was lower than or equivalent to bifenthrin(LC₅₀=1.96±0.21 mg/L).What’s more,three compounds were equivalent to deltamethrin and transfluthin(LC₅₀=0.38±0.08 and 0.51±0.12 mg/L)among them,in which the LC₅₀ values of these three compounds were BFA-3-1(LC₅₀=0.55±0.10 mg/L),BFA-3-2(LC₅₀=0.45±0.05 mg/L),and BFA-3-4(LC₅₀=0.53±0.12 mg/L),respectively,which were 3.5-4.5 times higher than that of bifenthrin.The results of anti-mosquito activity for resistant adult mosquito suggested that the activity of BFA-3-1,BFA-3-2 and BFA-3-4(LC₅₀ values were 1.28±0.19,0.94±0.35 and 0.89±0.40 mg/L,respectively)was 5-7 times higher than that of deltamethrin(LC₅₀=6.02±0.37 mg/L)and bifenthrin(LC₅₀=6.34±0.54 mg/L).Structure-activity relationship analysis implied that the target compound without theα-cyano group showed the most potential for anti-mosquito while tetrafluorophenyl phenyl ether was employed as the alcohol part and Lambda Cyhalothric acid was treated as the pyrethrin acid part of pyrethrin;when the para-substituents of the ether were electrondrawing groups of F,Cl and Br,the anti-mosquito potential of the compounds were better than that of the electron-donating groups of methyl,ethyl and vinyl.In addition,the photodegradation assay and toxicity on aquatic organisms of the highly active target compounds were comprehensively evaluated.The results of photodegradation assay indicated that the Half-life of BFA-3-1,BFA-3-2 and BFA-3-4(t_1/2=108.28-133.27min)were comparable to deltamethrin(t_1/2=77.00 min)and bifenthrin(t_1/2=94.93 min)under the same simulated sunlight irradiation.Meanwhile,the acute toxicity of BFA-3-1,BFA-3-2and BFA-3-4(96 h-LC₅₀ values were 0.67,0.54,0.47 mg/L,respectively)and their photodegradation products were lower than that of deltamethrin and bifenthrin obviously,in which the toxicity was approximately one-tenth of deltamethrin(96 h-LC₅₀=0.025 mg/L).In this study,54 target compounds were obtained by introducing tetrafluorophenyl into the structure of deltamethrin through organic synthesis.And the potential compounds of BFA-3-1,BFA-3-2 and BFA-3-4 were evaluated comprehensively based on the anti-mosquito activity,photostability and aquatic toxicity on Danio rerio.This study suggested that these most potential compounds could be used as novel pyrethroid pesticides to alleviate mosquito resistance and provide scientific basis for the development of novel anti-mosquito pesticides.