Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry , Central China Normal University (CCNU) , Wuhan 430079 , P.R. China.
State Key Laboratory of Elemento-Organic Chemistry , Nankai University (NKU) , Tianjin 300071 , P.R. China.
J Agric Food Chem. 2018 Apr 18;66(15):3773-3782. doi: 10.1021/acs.jafc.8b00665. Epub 2018 Apr 10.
The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine-biphenyl hybrids (4aa-bb and 5aa-ah) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds 4aa ( K = 0.09 μM) and 4bb ( K = 0.02 μM) displayed higher inhibitory activities against Arabidopsis thaliana AHAS than those of the controls bispyribac ( K = 0.54 μM) and flumetsulam ( K = 0.38 μM). Remarkably, compounds 4aa, 4bb, 5ah, and 5ag exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5-150 g of active ingredient (ai)/ha. Furthermore, 4aa and 4bb showed higher herbicidal activity against AHAS inhibitor-resistant Descurainia sophia, Ammannia arenaria, and the corresponding sensitive weeds than that of bispyribac at 0.94-0.235 g ai/ha. Therefore, the pyrimidine-biphenyl motif and lead compounds 4aa and 4bb have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds.
杂草对乙酰羟酸合酶（EC 2.2.1.6，AHAS）抑制剂的抗药性问题已成为此类除草剂应用的最大障碍之一。为了继续发现克服杂草抗性的新型 AHAS 抑制剂，我们通过支架跳跃策略设计并合成了一系列嘧啶-联苯类化合物（4aa-bb 和 5aa-ah）。在这些衍生物中，化合物 4aa（K = 0.09 μM）和 4bb（K = 0.02 μM）对拟南芥 AHAS 的抑制活性高于对照药剂双吡氟（K = 0.54 μM）和氟噻草胺（K = 0.38 μM）。值得注意的是，化合物 4aa、4bb、5ah 和 5ag 在 37.5-150 g ai/ha 的施用量下表现出优异的苗后除草活性和广谱除草活性。此外，化合物 4aa 和 4bb 在 0.94-0.235 g ai/ha 的用量下对 AHAS 抑制剂抗性播娘蒿、猪毛菜和相应的敏感杂草的除草活性均高于双吡氟。因此，嘧啶-联苯基序和先导化合物 4aa 和 4bb 具有发现新型 AHAS 抑制剂以对抗 AHAS 抑制性除草剂抗性杂草的巨大潜力。
