Design, Synthesis And Bioactivities Of Novel Ryanodine Receptor Insecticides

The discovery of new pesticide ryanodine receptor (RyR) insecticides with a unique mode of action have been developed successfully in recent years. This category of pesticides has broad-spectrum of activity, high efficiency, safety to non-target with no cross resistance, has attracted great attention of researchers. The phthalic diamides (Flubendiamide) and anthranilic diamides (chlorantraniliprole and cyantraniliprole) were discovered by the Nihon Nohyaku and DuPont Co, respectively. These two kinds of insecticides have different mechanisms from traditional insecticides in that they are the activators of insect ryanodine receptor, causing the uncontrolled release of internal calcium and ultimately leading to final mortality. Their results include feeding cessation, lethargy, paralysis, and death. There is a great structural difference between insect ryanodine receptor and the mammalian ryanodine receptor, and these new type of insecticide are safe to mammals.This paper summarizes the recent advance in mechanism of insect RyR, the latest research progress in this field at home abroad. Based on these collective information, nine series of127new compounds were designed and synthesized by applying such approaches as analogue synthesis, sub-structure coordination and bioisosterism principle. The structures were characterized by1H NMR,13C NMR, elemental analysis, HRMS and X-ray diffraction. Among the nine series, the2,3-dihydro-1,3,4-oxadiazole group was firstly introduced into aliphatic amide moiety as well as2,3-dihydroquinazolinone, quinazolinone, oxadiazole, diacylhydrazine, sulfonyl hydrazide, methylene amide bond, triazole ring and urea bridge. The insecticidal activity against oriental armyworm(Mythimna separata) and diamondback moth (Plutella xylostella) indicated that:the compounds containing the2,3-dihydro-1,3,4-oxadiazole group (Ⅲ) showed excellent insecticidal activity, which showed40%larvicidal activities against oriental armyworm at1mg/L. A novel method of forming oxadiazole ring was found during the synthesis of this series.In the transformation of the amido bridge, a series new bridge structures were introduced, but failed to obtained the structures with excellent insecticidal activity, within which only series IV, the diacylhydrazine series showed60%insecticidal activity at5ppm against oriental armyworm. The calcium imaging technique demonstrated that some compounds were possible ryanodine receptor activators. Fungicidal activities in vitro showed that:some compounds have good fungicidal activities, especially compound (VII), which deserves our further study.