摘要/Abstract

乙酰羟酸合成酶（Acetohydroxyacid synthase，AHAS）是一类重要的除草剂靶标，但是靶向AHAS的抑制剂是所有除草剂类型中抗性最为严重的一类，因此设计具有反抗性的AHAS抑制剂显得尤为必要.本工作基于前期低抗性AHAS抑制剂结构，利用“构象柔性度分析”的设计策略合理增加分子柔性，设计并合成了13个含“双氧桥”结构的嘧啶水杨酸类抑制剂.目标分子均经过氢谱（¹H NMR）、碳谱（¹³C NMR）和高分辨质谱（HRMS）确证.酶水平活性结果显示，部分化合物对P197L突变体表现出了微摩尔水平的抑制作用，特别是2-（（4，6-二甲氧基嘧啶-2-基）氧基）-6-（2-氟-4-硝基苯氧基）-4-甲基苯甲酸（6l）对P197L突变体表现出了良好的反抗性.盆栽除草活性结果表明，个别化合物对抗性杂草播娘蒿具有一定的除草活性，其中2-（（4，6-二甲氧基嘧啶-2-基）氧基）-6-（2-氟苯氧基）-4-甲基苯甲酸（6b）在150 g ai/ha浓度下，对敏感生物型播娘蒿和抗性播娘蒿均达到80%的除草防效，具有进一步深入研究的价值.
关键词: 乙酰羟酸合成酶, 反抗性, P197L突变体, 构象柔性, 抗性杂草
Acetohydroxyacid synthase (AHAS) was one of important herbicidal targets. However, the issue of weed resistance to commercial AHAS inhibitors has become one of the largest obstacles for their application. Therefore, there is a high demand to design new anti-resistance AHAS inhibitors. Herein, based on the reported low resistance AHAS inhibitors, a series of pyrimidyl-salicylates with "double oxygen bridge" utilized the "conformation flexibility analysis" strategy were designed. All the synthesized compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. The bioactivity results showed that most of the derivatives displayed good inhibitory activities against P197L mutant. Especially, 2-((4,6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluoro-4-nitrophenoxy)-4-methylbenzoic acid (6l) was identified as the most potent anti-resistance AHAS inhibitor. In addition, some compounds showed good weed control for resistant Descurainia sophia (P197L AHAS). Most importantly, 2-((4,6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluorophenoxy)-4-methylbenzoic acid (6b) showed 80% herbicidal activities against sensitive and resistant Descurainia sophia at the dosage of 150 g ai/ha. These results indicated that this type of compounds worth of the further investigation.
Key words: acetohydroxyacid synthase, anti-resistance, P197L mutant, conformation flexibility, resistant weed


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