双取代嘧啶-联苯化合物的合成及除草活性和分子作用机制研究
收稿日期: 2024-05-25
修回日期: 2024-06-25
网络出版日期: 2024-07-25
基金资助
国家自然科学基金(31471807)
Synthesis and Herbicidal Activity of Di-substituted Pyrimidine-Biphenyls and Study of Molecular Mode of Action
Received date: 2024-05-25
Revised date: 2024-06-25
Online published: 2024-07-25
Supported by
National Natural Science Foundation of China(31471807)
以嘧啶-联苯化合物1为先导结构, 向其δ-环引入双取代基, 设计并合成了一系列双取代嘧啶-联苯化合物. 目标化合物均经过核磁共振氢谱(1H NMR)、碳谱(13C NMR)、氟谱(19F NMR)和高分辨质谱(HRMS)确证. 温室盆栽除草活性结果表明, 在750 g a.i./ha剂量下大部分化合物对稗草、马唐和反枝苋具有较高的芽后除草活性, 特别是N-(2-((4,6-二甲氧基嘧啶-2-基)氧基)苄基)-3'-甲氧基-5'-甲基-[1,1'-联苯基]-2-胺(4f), 对所测试的四种杂草的芽前和芽后平均除草防效达到81%, 表现出广谱的芽前和芽后除草活性. 分子作用机制研究发现, 4f的作用靶标为乙酰羟酸合成酶(AHAS), 4f与AHAS疏水空腔中的残基形成广泛的疏水相互作用, 增强了与残基M352、V485以及辅因子黄素腺嘌呤二核苷酸(FAD)的相互作用, 从而使4f (IC50=98.1 μmol/L)具有相较于先导结构1 (IC50=157 μmol/L)更强的AHAS抑制活性. 结果表明4f具有进一步深入研究的价值.
关键词： 乙酰羟酸合成酶抑制剂; 联苯; Suzuki偶联; 除草活性; 分子对接
颜逸韬 , 陈颖露 , 胡涵显 , 吴军 . 双取代嘧啶-联苯化合物的合成及除草活性和分子作用机制研究[J]. 有机化学, 2025 , 45(1) : 358 -366 . DOI: 10.6023/cjoc202405035
Starting from the pyrimidine-biphenyl compound 1 as a lead structure, a series of di-substituted pyrimidine-biphenyl compounds were designed and synthesized by introducing disubstituents to its δ-ring. All the target compounds were characterized by 1H NMR, 13C NMR, 19F NMR, and HRMS. The results of herbicidal activity evaluation in the greenhouse assay showed that most of the compounds exhibited excellent herbicidal activity against Echinochloa crusgalli, Digitaria san- guinalis, and Amaranthus retroflexus in post-emergence treatments. Notably, N-(2-((4,6-dimethoxypyrimidin-2-yl)oxy)-benzyl)-3'-methoxy-5'-methyl-[1,1'-biphenyl]-2-amine (4f) demonstrated an average pre- and post-emergence weed control of 81% against four tested weeds, exhibiting broad-spectrum herbicidal activities. The study of molecular mode of action revealed that the target compound 4f was acetohydroxyacid synthase (AHAS). 4f established extensive hydrophobic interactions with the residues within the hydrophobic cavity of AHAS, particularly enhancing the interactions with residues M352, V485, and the cofactor flavin adenine dinucleotide (FAD). Consequently, 4f (IC50=98.1 μmol/L) exhibited higher AHAS inhibitory activity compared to the lead structure 1 (IC50=157μmol/L). These findings suggested that 4f was worthy of further investigation.
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