Synthesis,Bioactivities And Phloem Uptake Of Dipeptide-chlorantraniliprole Derivatives

Phloem systemicity is a desirable property for insecticides to control sucking insects,and can reduce pesticide use while improving pesticide targeting and utilization.,thereby reducing environmental pollution.Under the characteristics of absorption and transportation by plant endogenous compounds（sugars,amino acids,dipeptides）,coupling existed insecticides with plant endogenous substances so that the resulting conjugates can be transported by specific transporters into the phloem.Under the guidance of the guiding pesticide concept,novel dipeptide promoieties were introduced into chlorantraniliprole,which is an efficient and broad-spectrum anthranilic diamide insecticide without phloem mobility.Twenty-two new dipeptide-chlorantraniliprole conjugates have been synthesized,all conjugates were confirmed by ¹H NMR,¹³C NMR and ESI-HRMS.Systemic tests showed that all conjugates exhibited phloem mobility in Ricinus communis.In particular,compound 4g with alanyl-alanine dipeptide fragment was able to accumulate in phloem sap（114.49±11.10μM）in the form of its hydrolysis product5g.This indicates that the pesticide of phloem mobility can be obtained by attaching a dipeptide fragment.By comparing the difference between the absorbing amounts of the conjugates,it was found that the substituent R of theαposition in the structure of the amino acid residue in the dipeptide fragment was related to the transport of the conjugate in plants.When the R was CH₃,the phloem of the conjugate had the best phloem mobility;When the steric hindrance of the substituent increased,the phloem mobility of the conjugate decreased;When the substituent contained a benzene ring,the phloem mobility of the conjugate was significantly reduced.According to the prediction of the Kleier model,a total of six conjugates（5a,5b,5e,5f,5g,5i）were located in the mobile region of passive diffusion,and 16 compounds are located in the region without passive diffusion,indicating that passive diffusion was not the main pathway for the conjugate to enter the phloem phloem.It is speculated that there may be active transport under the mediated transport of the dipeptide.Results of bioassay showed that conjugates 4g and 5g were able to exhibited comparable insecticidal activity against Plutella xylostella and Spodoptera exigua compared to its parent compound chlorantraniliprole.This work is the first application of dipeptide fragments to pesticide research.Different types of dipeptide-chlorantraniliprole conjugates and dipeptide ester-chlorantraniliprole conjugates have been synthesized.It was demonstrated that the dipeptide structures were able to contribute to the improvement of the uptake and phloem mobility of chlorantraniliprole.The prediction of the Kleier model indicates that the active transport participated in the absorption and transport of the conjugate.And two phloem mobile conjugates with satisfactory in vivo insecticidal effect was obtained as new candidates for high-efficient insecticides.