1,2,4-三唑酰胺类转酮醇酶抑制剂的合成及除草活性研究

Synthesis of 1,2,4-triazole amides as transketolase inhibitors with improved herbicidal activity

本研究基于除草剂新靶标转酮醇酶,采用骨架跃迁的方法对化合物5aw进行了先导优化,通过酰胺键和硫醚键将噻吩、嘧啶、1,2,4-三唑等活性亚结构拼接,设计合成了5个1,2,4-三唑酰胺类化合物8(a-e),所有目标化合物均经IR、MS和;H NMR验证。除草活性测试结果表明,8b和8d具有比阳性对照丙炔氟草胺更优异的除草活性;构效关系研究表明,氯原子取代基有利于提高化合物的除草活性。荧光结合实验表明,化合物8b,8d与转酮醇酶之间亲和力更高,这是由于形成了更稳定的络合物,从而导致它们对此酶产生更强的抑制活性,因此,化合物8b和8d有潜力作为转酮醇酶抑制剂类除草先导化合物,值得进一步结构优化。

Transketolase(TK) has been identified as a new herbicide target. In this study, five 1,2,4-triazole amide compounds 8(a-e) were synthesis with compound 5aw by optimization using the method of scaffold hopping and splicing with active substructure thiophene, pyrimidine and 1,2,4-triazole via amide and thioether bonds, followed by verification with IR, MS and ~1H NMR. Then the herbicidal activity examination showed that 8b and 8d displayed better herbicidal activity than flumioxazin that was set as the positive control. Structure-activity relationship analysis show that the substituent Cl was beneficial for improving the herbicidal of compounds. Fluorescence binding experiments showed that compounds 8b and 8d had higher affinity with TK caused by forming more stable complexes with TK. Our study provided two potential herbicidal lead compounds targeting TK, which deserved further structural optimization.