期刊论文

Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors

Chen Qiong;Yang Guangfu

中文

有机化学

0253-2786

2019

39

8

2303-2310

10.6023/cjoc201901043

National Key Research and Development Program of China [2018YFD0200102]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21837001, 21772058]

本校为第一且通讯机构

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(~(13)C 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(61)对P197L突变体表现出了良好的反...

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...