Synthesis Of Novel Guided Pesticides With Diamide Structure And Their Phloem Mobility

It is estimated that only a very small part of pesticides applied in fields?less than0.1%?can reach the sites of action while the off-target portion becomes environment pollutant.How to reduce pesticide usage without affecting the quantity and quality of agricultural products is one of the great challenges of the 21st century.Thus,new environment friendly agrochemicals with optimal efficacy are needed for sustainable agriculture.Conjugating amino acid and glucose fragments with existed pesticide structures has been proven to be an effective way to introduce phloem mobility to non-phloem mobile species and obtain“guided pesticides”with enhanced efficiency.However,the resulting derivatives always suffered from lower bioactivity compared to their parent compound.To solve this problem,herein,we designed and synthesized a series of ester-capped amino acid conjugated chlorantraniliprole.In this thesis,On the basis of the commercial insecticide chlorantraniliprole,a series of novel N-pyridylpyrazolecarboxamides containing an amino acid fragment were designed and synthesized.Their chemical structures were established on the basis of corresponding ¹H NMR spectroscopy?¹³C NMR spectroscopy and MS.The systemic test showed that all of conjugates exhibited phloem mobility in Ricinus communis model.Particularly,compounds C-7b?Glycine methyl ester conjugate?,C-8b?L-Alanine methyl ester conjugate?,C-8c?L-Alanine ethyl ester conjugate?,D-16b?L-Methionine methyl ester conjugate?,E-19a??-aminobutyric acid conjugate?,E-19b??-aminobutyric acid methyl ester conjugate?,E-20b?5-aminovaleric acid methyl ester conjugate?and E-21b?6-aminocaproate acid methyl ester conjugate?were able to accumulate in phloem tissues in the form of their hydrolysis products,and the concentrations in phloem sap can reach three times as high as the concentration in incubation medium.Although their insecticidal activity(LC₅₀)against beet armyworm?Spodoptera exigua?in vitro were weaker than chlorantraniliprole,compounds C-7b,C-8b and C-8c showed similar insecticidal activity in vivo against beet armyworm compared to the parent compound.Two passive diffusion models,Kleier model and“Rule of Five”were employed to predict the permeability and phloem mobility of test compounds C-7?a-c?,C-8?a-c?and C-8?a-c?.The results demonstrated that both of the tested compounds were with poor permeability and non-phloem-mobility.The good phloem mobility of conjugates in Ricinus test can not be explained well by passive diffusion rules,the vast differences between experiment and prediction indicated that it is likely an active carrier-mediated mechanism is also involved in the uptake of test compounds.To investigate the insecticidal activities of new compounds and chlorantraniliprole against beet armyworm,the leaf disk dipping assay was used for evaluation.Compounds C-7?b-c?,C-8?b-c?,D-16?a-c?and E-18?b-c?showed good activity against beet armyworm at the seven concentrations being tested.Especially,amino acid ester derivative D-16c exhibited comparable activity than that of chlorantraniliprole(LC₅₀=0.13 mg/L)with the LC₅₀ being0.22 mg/L.Compounds C-7b,C-8b and C-8c with significant accumulation level in phloem sap were also selected to compare with chlorantraniliprole on insecticidal activity in vivo at a low concentration.No significant difference was observed on the mortality of beet armyworm for conjugates in nutrient solution at 50?M compared to chlorantraniliprole.The result indicated that the decreased bioactivity of amino acid ester conjugates caused by structural modification could be compensated by the increased concentration in phloem and xylem sap.This work has provided a novel strategy to obtain high-efficient pesticide derivatives that possessing both improved uptake and mobility in crops while retaining the insecticidal activity of the parent compound.