Design and Synthesis of Indole-Containing Tetrahydrothiazolo[3,2- a ]pyrimidine Mesoionics against Hemipteran Pests

作者：Yuqin Luo, Shang Wu, Zhongjie Shen, Jiao Li, Yanju Wang, Deyu Hu, Baoan Song · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c02233 · 被引用次数：3 · 研究领域：Insect and Pesticide Research、Synthesis and Biological Evaluation、Insect-Plant Interactions and Control

Mesoionic insecticides have emerged as promising pest nAChR modulators devoid of cross-resistance with neonicotinoids, demonstrating exceptional efficacy against sap-feeding insects. Nevertheless, the tetrahydrothiazolo[3,2- a ]pyrimidine structure remains underexplored within this chemotype. Here, we report an indole-based scaffold hopping of tetrahydrothiazolo[3,2- a ]pyrimidine, which leads to the development of a series of novel mesoionics. Their insecticidal potency is evaluated against the hemipteran pest Acyrthosiphon pisum ( A. pisum ) and Sogatella furcifera ( S. furcifera ). Derivative G 1 exhibits excellent aphicidal activity (LC 50 = 5.11 mg/L), comparable to triflumezopyrim (TFM) (3.71 mg/L) though less than fenmezoditiaz (1.03 mg/L). Chirally resolved ( R ) -G 1 displays enhanced efficacy against A. pisum (LC 50 = 2.12 mg/L). Notably, G 1 demonstrates significantly lower acute contact toxicity to honeybees (LD 50 = 27.66 μg/bee) versus TFM (highly toxic, 0.66 μg/bee) and fenmezoditiaz (moderately toxic, 5.12 μg/bee). Enzymatic assays, ELISA, and proteomics suggest G 1 ’s disruptive impacts on neuronal pathways. Molecular docking shows strong binding of ( R ) -G 1 to Aplysia californica AChBP via hydrogen bonds with residues IleC106, TrpD147, and TyrD195. This study identifies G 1 as a potent insecticide lead with favorable pollinator safety.