Design and synthesis of mesoionic compounds containing benzoxacycle for the control of piercing-sucking pests.

Piercing-sucking pests cause significant agricultural losses, and widespread neonicotinoid use has led to resistance and ecological concerns. Mesoionic compounds show broad-spectrum insecticidal activity with low cross-resistance, yet the mechanism and potential of tetrahydrothiazolo[3,2-a]pyrimidine mesoionic scaffolds against these pests remain largely unexplored. Here, a series of novel tetrahydrothiazolo[3,2-a]pyrimidine mesoionics containing a benzoxacycle moiety were designed, synthesized, and evaluated for insecticidal activity against Megoura crassicauda (M. crassicauda) and Sogatella furcifera (S. furcifera). All compounds showed notable bioactivity, with H1 displaying the highest aphicidal potency (LC50 = 1.08 mg/L) and its enantiomer (R)-H1 exhibiting markedly enhanced activity (LC50 = 0.31 mg/L), superior to triflumezopyrim (TFM, LC50 = 2.13 mg/L) and comparable to fenmezoditiaz (LC50 = 0.16 mg/L). Acute contact toxicity assays demonstrated that (R)-H1 was substantially less toxic to honeybees (LD50 = 4.58 μg/bee) than TFM (LD50 = 0.55 μg/bee) and fenmezoditiaz (LD50 = 1.28 μg/bee). Mode of action studies, including enzyme activity assays and ELISA, suggest that (R)-H1 interferes with the neural function of aphids. DFT calculations and molecular docking further support the stable, stereoselective binding of (R)-H1 to AChBP, providing a molecular basis for the observed enantioselective activity. Collectively, these findings highlight (R)-H1 as a promising lead for developing environmentally benign insecticides targeting piercing-sucking pests.