The structure modification of seven-membered aza-brigded neonicotinoids in order to investigate their impact on honey bees

Abstract

In order to explore the relationship between the structure and the toxicity to honey bees of seven-membered aza-bridged neonicotinoids, 16 novel seven-membered aza-bridged neonicotinoid analogues are synthesized by replacing the pyridine ring, and changing the substituents on the pyridine ring, the electron-withdrawing group NO2 and the imidazole ring of our previously developed aza-bridged neonicotinoid 1-[(6-chloropyridin-3-yl)methyl)]-10-(2,5-dimethylphenyl)-9-nitro-2,3,5,6,7,8-hexahydro-1 H-5,8-epiminoimidazo azepine (C-29). The insecticidal bioactivities against cowpea aphid ( Aphis craccivora) and the bee toxicities of these compounds are tested. Some of the title compounds present good insecticidal activities against cowpea aphid. The results also show that some of the title compounds exhibit lower bee toxicity than that of C-29 and imidacloprid. This suggests that changing the substituents on the neonicotinoids can influence the toxicity toward honey bees of these analogues.

Controllable Synthesis of Trifluoromethyl- or gem-Difluorovinyl-containing Analogues of Neonicotinoids by the Reaction of α-(Trifluoromethyl)styrenes with 2-Nitroimino-imidazolidine

“…All solvents were of analytical grade, unless otherwise mentioned, and solvents and reagents were received from commercial suppliers and used without further purification. α-(Trifluoromethyl)styrenes 1 [41,42], 2-(nitromethylene)imidazolidine 2b, and 2-(nitromethylene)hexahydropyrimidine 2e were synthesized by previously reported methods [43]. 2-Nitroimino-imidazolidine 2a, 2-cyanoimino-thiazolidine 2c, (E)-1-methyl-2-nitroguanidine 2d, 3-methyl-4-nitroimino-tetrahydro-1,3,5-oxadiazine 2f, and 2-cyanoguanidine 2g were purchased from commercial sources.…”

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids

“…In addition to being a neonicotinoid moiety, thiazolidine is also the fragment of the low bee toxic ci s-phenylthio-thiazolidinylidene-acetonitrile fungicide flutianil . Meanwhile, the cis -conformation draw our attention to the rational design of cis -neonicotinoids, which stimulated the process of identifying new neonicotinoids with low bee toxicity. − Inspired by the above considerations, a series of novel cis -thiazolidinylidene-acetonitrile compounds, which bear the neonicotinoid insecticidal cyanide polar group and 6-Cl-pyridin-3-yl, 6-CF 3 -pyridin-3-yl, or 5-Cl-thiazo-2-yl fragments, were rationally designed and synthesized by active substructure splicing strategy (Figure ), and the insecticidal activities against A. craccivora were then evaluated. Molecular docking, quantum chemical computational analysis as well as bee toxicity prediction were performed to verify the binding mode with the target and potential low bee toxicity mechanism of the target compounds.…”