含环丙基的新型取代嘧啶-5-甲酰胺的合成及杀菌活性研究
收稿日期: 2023-07-31
修回日期: 2022-09-17
网络出版日期: 2023-10-12
基金资助
山东省自然科学基金(ZR2020MB110)
Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety
Received date: 2023-07-31
Revised date: 2022-09-17
Online published: 2023-10-12
Supported by
Natural Science Foundation of Shandong Province(ZR2020MB110)
为发现具有优异杀菌活性的新型嘧啶类化合物, 采用活性亚结构拼接法设计合成了13种N-(取代苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺及3种不含环丙基的类似物, 其结构经核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)、红外光谱(IR)和高分辨质谱(HRMS)鉴定. 利用菌丝生长速率法测定了化合物对植物病原菌的杀菌活性, 在浓度为100 mg/L时, 部分化合物显示出较高的杀菌活性, 其中N-(4-氯苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4e)、N-(4-溴苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4h)和N-(3,4-二氯苯基)-2-环丙基-4-甲基嘧啶-5-甲酰胺(4k)对灰霉菌的抑制率分别为87.9%、84.4%和85.2%, 4k对菌核菌的抑制率为84.6%. 进一步试验显示4k对灰霉菌的抑制中浓度为4.67 mg/L, 其活性与对照药剂嘧菌环胺相当且高于啶酰菌胺. 与不含环丙基的4-甲基嘧啶-5-甲酰胺的比较揭示了嘧啶环上引入环丙基有利于提高化合物的杀菌活性.
李鹏辉 , 谢青洋 , 万福贤 , 张元红 , 姜林 . 含环丙基的新型取代嘧啶-5-甲酰胺的合成及杀菌活性研究[J]. 有机化学, 2024 , 44(2) : 650 -656 . DOI: 10.6023/cjoc202307029
In order to develop novel pyrimidine compounds with excellent fungicidal activity, thirteen N-substituted phenyl-2- cyclopropyl-4-methylpyrimidine-5-carboxamides and three analogues without cyclopropyl moiety were designed and synthesized by means of the active substructure splicing method. The structures of target compounds were characterized by1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), infrared spectrometry (IR) and high-resolution mass spectra (HRMS). The preliminary fungicidal activities against plant fungi were evaluated, and the result revealed that some compounds exhibited high activity at a concentration of 100 mg/L. For example, N-(4-chlorophenyl)- 2-cyclopropyl-4-methylpyrimidine-5-carboxamide(4e), N-(4-brorophenyl)-2-cyclopropyl-4-methylpyrimidine-5-carboxamide (4h) and N-(3,4-dichlorophenyl)-2-cyclopropyl-4-methylpyrimidine-5-carboxamide(4k) showed inhibitory rates of 87.9%, 84.4% and 85.2% against Botrytis cinerea, respectively, and 4k showed inhibitory rate of 84.6% against Sclerotinia sclerotiorum. Further bioassay indicated that 4k possessed a lower effective concentration value of 4.67 mg/L, which meant that its activity was comparable to that of cyprodimol and was higher than that of boscalid. A bioactivity comparison between target compounds and the analogues without cyclopropyl moiety, demonstrated that the intrduction of cyclopropyl to the pyrimidine ring is beneficial for improving the fungicidal activity.
Key words： pyrimidine; cyclopropyl; amide; synthesis; fungicidal activity
| [1] | Xiao, Z.; Zhou, Z. H.; Chu, C. L.; Zhang, Q.; Zhu, W. F. Eur. J. Med. Chem. 2020, 203, 112511. |
| [2] | Tanase, C. I.; Draghici, C.; Cojocaru, A.; Galochkina, A. V.; Maganu, M. Bioorg. Med. Chem. 2015, 23, 6346. |
| [3] | Castano, L. F.; Cuartas, V.; Bernal, A.; Insuasty, A.; Insuasty, B. Eur. J. Med. Chem. 2019, 176, 50. |
| [4] | Zhang, J.; Song, R. J.; Wu, S.; Cai, D.; Wu, Z. X.; Liu, Z. J.; Hu, D. Y.; Song, B, A. J. Agric. Food Chem. 2021, 69, 15136 |
| [5] | Sun, C. X.; Zhang, S.; Qian, P.; Li, Y.; Deng, H.; Ren, W. S.; Jiang, L. Bioorg. Med. Chem. Lett. 2021, 47, 128210. |
| [6] | Wang, W.; Wang, J. H.; Wu, F. R.; Zhou, H.; Xu, D.; Xu, G. J. Agric. Food Chem. 2021, 69, 5746. |
| [7] | Liu, C. L.; Liu, P. F.; Li, M. A Complete Collection of World Agrochemicals Fungicide. 2nd ed., Chemical Industry Press, Beijing, 2021 (in Chinese). |
| [7] | (刘长令, 刘鹏飞, 李淼, 世界农药大全?杀菌剂卷, 第二版, 化学工业出版社, 北京, 2021.) |
| [8] | Wei, B.-B.; Han, C.; Shang, P.-P.; Guo, X.-Y.; Bai, L.-G.; Ma, Z.-Y. Med. Chem. Res. 2022, 31, 1901. |
| [9] | Vara, B. A.; Levi, S. M.; Achab, A.; Candito, D. A.; Fradera X, Pasternak A. ACS Med. Chem. Lett. 2021, 12, 653. |
| [10] | Iraji, A.; Nouri, A.; Edraki, N.; Pirhadi, S.; Khoshneviszadeh, M.; Khoshneviszadeh, M. Bioorg. Med. Chem. 2020, 28, 115359. |
| [11] | Wang, S. C.; Wan, F. X.; Liu, S.; Zhang, S.; Jiang, L. J. Chin. Chem. Soc. 2018, 65, 445. |
| [12] | Shi, Y. H.; Zhang, S.; Wan, F. X.; Sun, C. X.; Jiang, L. Chin. J. Org. Chem. 2020, 40, 1948 (in Chinese). |
| [12] | (时艳华, 张帅, 万福贤, 孙昌兴, 姜林, 有机化学. 2020, 40, 1948.) |
| [13] | Chen, R. J.; Zhou, C.; Pang, X. W.; Liu, J. J.; Gu, Y. C.; Liu, J. W.; Li, Z. Chin. J. Org. Chem. 2022, 42, 277 (in Chinese). |
| [13] | (陈睿嘉, 周聪, 逄锡文, 刘佳君, 顾玉诚, 刘建文, 李忠, 有机化学. 2022, 42, 277.) |
| [14] | Talele T. T. J. Med. Chem. 2016, 59, 8712. |
| [15] | Chen, L. P.; Wu, C. X.; Chang, T.; Xu, M. F.; Liu, C. X.; Wu, S. G.; Zhao, X. P. J. Zhejiang Agric. Sci. 2018, 59, 1535 (in Chinese). |
| [15] | (陈丽萍, 吴长兴, 苍涛, 徐明飞, 柳采秀, 吴声敢, 赵学平, 浙江农业科学. 2018, 59, 1535.) |
| [16] | Li, X.-L.; Shan, Y.-Q.; Ye, D.-B.; Zhang, Q.-Z.; Zheng, X.-H. Chin. J. Synth. Chem. 2008, 16, 239 (in Chinese). |
| [16] | (李小玲, 单玉庆, 叶大炳, 张群正, 郑晓晖, 合成化学. 2008, 16, 239.) |
| [17] | Sun, J. L.; Mu, W. Pesticide Science Experimental Techniques and Guidance. Chemical Industry Press, Beijing, 2009 (in Chinese). |
| [17] | (孙家隆, 慕卫, 农药实验技术与指导, 化学工业出版社, 北京, 2009.) |
| [18] | Shen, J. S.; Wang, B.; Li, J. F.; Lei, L. J.; Gi, R. Y. Chin. J. Pharm. 2001, 32, 49 (in Chinese). |
| [18] | (沈敬山, 王斌, 李剑峰, 雷厉军, 嵇汝运, 中国医药工业杂志. 2001, 32, 49.) |
/
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