Deuteration-Based Design, Green Synthesis, and Insecticidal Activity of Hexacyclic Pyrazol-3-amide Derivatives as Insect Growth Regulators

文献类型： 外文期刊

第一作者： Luo, Shihui

作者： Luo, Shihui;Guo, Bingbo;Liu, Yan;Feng, Yanjiao;Cao, Congwang;Zhang, Li;Yang, Xinling;An, Jie;Chen, Lei;Yang, Qing;Chen, Lei;Yang, Qing

作者机构：

关键词： deuteration strategy; reductive deuteration; 2-methyltetrahydrofuran; insect growth regulators; insecticidal activity; mechanism

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.2； 五年影响因子：6.4 ）

ISSN： 0021-8561

年卷期： 2025 年 73 卷 16 期

页码：

收录情况： SCI

摘要： The deuterium kinetic isotope effect (DKIE) underscores the stability of C-D bond, which can improve pharmacokinetic properties and reduce toxicity in compounds. Herein, the application of the deuteration strategy to improve the activity of insect growth regulators (IGRs) by replacing the C-H bond with a C-D bond at the benzylic position, known as the "soft spot", is first investigated. The corresponding deuterated intermediates were obtained through a novel green and efficient method utilizing samarium diiodide (SmI2) as a reductive deuterating agent and 2-methyltetrahydrofuran (2-MTHF) as a solvent to address environmental concerns. Subsequently, six deuterated compounds (D-1 to D-6) of hexacyclic pyrazol-3-amide derivatives are synthesized and compared in terms of insecticidal activity against Plutella xylostella, revealing lower LC50 values than nondeuterated compounds (H-1 to H-6). Particularly, compound D-3 exhibited significantly better activity (LC50: 11 mg/L) than H-3 (LC50: 197 mg/L), even higher than commercial tebufenozide. Additionally, the inhibitory activities against ecdysone receptor/ultraspiracle protein (EcR/USP) and three chitinases-OfChtI, OfChtII, and OfChi-h-demonstrate that deuteration enhances binding affinity specifically to the Chitinase OfChtI. After deuteration, the compounds exhibited a lower ClogP value and reduced energy gap, along with a slight reduction in lipophilicity and electrostatic potential, which together may contribute to improved activity. This work suggests that deuteration strategy is a promising approach to improve the compounds' efficacy for pest control.

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