Design, Synthesis, and Synergistic Activity of Eight-Membered Oxabridge Neonicotinoid Analogues

Abstract

Insecticide synergists are sought-after due to their potential in improving the pesticide control efficacy with a reduced dose of an active ingredient. We previously reported that a cis-configuration neonicotinoid (IPPA08) exhibited specific synergistic activity toward neonicotinoid insecticides. In this study, we synthesized a series of structural analogues of IPPA08 by converting the pyridyl moiety of IPPA08 into phenyl groups, via facile double-Mannich condensation reactions between nitromethylene compounds and glutaraldehyde. All of the oxabridged neonicotinoid compounds were found to increase the toxicity of imidacloprid against <i>Aphis craccivora</i>. Notably, compound <b>25</b> at 0.75 mg/L lowered the LC₅₀ value of imidacloprid against <i>A. craccivora</i> by 6.54-fold, while a 3.50-fold reduction of the LC₅₀ value was observed for IPPA08. The results of bee toxicity test showed that compound <b>25</b> display selectivity in its effects on imidacloprid toxicity against the honey bee (<i>Apis mellifera</i> L.). In summary, replacing the pyridyl ring with a phenyl ring was a viable approach to obtain a novel synergist with oxabridged moiety for neonicotinoid insecticides.