5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究
收稿日期: 2020-10-30
修回日期: 2020-11-25
网络出版日期: 2021-02-22
基金资助
国家自然科学基金(31701827); 中国博士后科学基金(2020M671984); 聊城大学博士科研启动基金(318051647); 聊城大学大学生创新创业训练(CXCY2020Y179); 山东省自然科学基金(ZR2019PC041)
Synthesis and Herbicidal Activity of 5-(1-Amino-2-phenoxyethylidene)barbituric Acid Derivatives
Received date: 2020-10-30
Revised date: 2020-11-25
Online published: 2021-02-22
Supported by
National Natural Science Foundation of China(31701827); China Postdoctoral Science Foundation(2020M671984); Doctoral Research Startup Foundation of Liaocheng University(318051647); Innovation and Entrepreneurship Training Program for College Students of Liaocheng University(CXCY2020Y179); Natural Science Foundation of Shandong Province(ZR2019PC041); National Natural Science Foundation of China(21675071)
基于具有生物活性的烯胺二酮骨架及前期报道的先导化合物5-酰基巴比妥酸I的结构, 设计、合成了26个结构新颖的5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物. 生物活性测试结果表明, 化合物5-(2-(2-氯-4-氟苯氧基)-1-(戊基氨基)亚乙基)-1,3-二甲基嘧啶-2,4,6(1H,3H,5H)-三酮(APB-5)在苗后处理, 187.5 g?ha–1剂量时, 对双子叶植物(油菜、苋菜)具有100%的抑制活性. 更重要的是, 化合物APB-5在375 g?ha–1的剂量时具有宽的除草谱且对玉米、小麦和谷子安全, 这说明该化合物具有成为除草剂的潜力. 此外, 通过研究拟南芥的表型及化合物对激素响应基因的影响发现, 化合物APB-5具有与激素类除草剂2,4-二氯苯氧乙酸(2,4-D)相似的作用机制. 目前的研究表明, 化合物APB-5可以作为进一步开发新型生长素类除草剂的先导结构.
王超超 , 刘会 , 赵微 , 李攀 , 冀庐莎 , 柳仁民 , 雷康 , 徐效华 . 5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究[J]. 有机化学, 2021 , 41(5) : 2063 -2073 . DOI: 10.6023/cjoc202010042
Based on the bioactive enamino diketone skeleton and the structure of our previously reported lead compound 5-acylbarbituric acid I, twenty-six novel 5-(1-amino-2-phenoxyethylidene)barbituric acid derivatives were designed and synthesized. The bioassay results showed that the analog 5-(2-(2-chloro-4-fluorophenoxy)-1-(pentylamino)-ethyli- dene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (APB-5) displayed excellent post-emergent herbicidal activity, with inhibition 100% against dicotyledonous plants (Brassica campestris, Amaranthus retroflexus), even at a dosage of 187.5 g? ha–1. More importantly, compound APB-5 showed a broad spectrum of weed control and displayed good crop safety toward wheat, maize and millet, when applied at 375 g?ha–1, indicating its remarkable potential as a herbicide. Furthermore, by investigating the phenotypes of Arabidopsis thaliana and analyzing the effect of compound APB-5 on auxin response genes in plants, it was found that compound APB-5 had a herbicidal mechanism similar to auxin-type herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D). Taken together, the present work demonstrated that compound APB-5 could serve as a lead structure for further developing novel auxin-type herbicides.
Key words： barbituric acid; enamino diketone; synthesis; herbicidal activity; auxin
| [1] | Gross, E. M.; Wolk, C. P.; Jüttner, F. J. Phycol. 1991, 27, 686. |
| [2] | Ding, L.; Dahse, H.-M.; Hertweck, C. J. Nat. Prod. 2012, 75, 617. |
| [3] | Avdovi?, E. H.; Stojkovi?, D. L.; Jevti?, V. V.; Milenkovi?, D.; Markovi?, Z. S.; Vukovi?, N.; Poto?ňák, I.; Radojevi?, I. D.; ?omi?, L. R.; Trifunovi?, S. R. Inorg. Chim. Acta 2019, 484, 52. |
| [4] | Mladenovi?, M.; Vukovi?, N.; Ni?iforovi?, N.; Sukdolak, S.; Soluji?, S. Molecules 2009, 14, 1495. |
| [5] | Baldwin, A. G.; Bevan, J.; Brough, D.; Ledder, R.; Freeman, S. Med. Chem. Res. 2018, 27, 884. |
| [6] | Garmaise, D. L.; Chu, D. T. W.; Bernstein, E.; Inaba, M. J. Med. Chem. 1979, 22, 559. |
| [7] | Canela, M. D.; Pe?rez-Pe?rez, M. J.; Noppen, S.; Sa?ez-Calvo, G.; Díaz, J. F.; Camarasa, M. J.; Liekens, S.; Priego, E. M. J. Med. Chem. 2014, 57, 3924. |
| [8] | Ili?, D. R.; Jevti?, V. V.; Radi?, G. P.; Arsikin, K.; Risti?, B.; Harhaji-Trajkovi?, L.; Vukovi?, N.; Sukdolak, S.; Klisuri?, O.; Trajkovi?, V.; Trifunovi?, S. R. Eur. J. Med. Chem. 2014, 74, 502. |
| [9] | Budzisz, E.; Keppler, B. K.; Giester, G.; Wozniczka, M.; Kufelnicki, A.; Nawrot, B. Eur. J. Inorg. Chem. 2004, 2004, 4412. |
| [10] | Budzisz, E.; Ma?ecka, M.; Lorenz, I. P.; Mayer, P.; Kwiecien, R. A.; Paneth, P.; Krajewska, U.; Rozalski, M. Inorg. Chem. 2006, 45, 9688. |
| [11] | Budzisz, E.; Brzezinska, E.; Krajewska, U.; Rozalski, M. Eur. J. Med. Chem. 2003, 38, 597. |
| [12] | Dias, L. C.; Demuner, A. J.; Valente, V. V. M.; Barbosa, L. C. A.; Martins, F. T.; Doriguetto, A. C.; Ellena, J. J. Agric. Food Chem. 2009, 57, 1399. |
| [13] | Serban, A.; Watson, K. G.; Bird, G. J.; Farquharson, G. J.; Cross, L. E. US 4952722, 1990. |
| [14] | Liu, Y. X.; Zhao, H. P.; Wang, Z. W.; Li, Y. H.; Song, H, B.; Riches, H.; Beattie, D.; Gu, Y. C.; Wang, Q. M. Mol. Diversity 2013, 17, 701. |
| [15] | Batran, R. Z.; Khedr, M. A.; Abdel Latif, N. A.; Abd El Aty, A. A.; Shehata, A. N. J. Mol. Struct. 2019, 1180, 260. |
| [16] | Lv, P.; Chen, Y. L.; Zhao, Z.; Shi, T. Z.; Wu, X. W.; Xue, J. Y.; Li, Q. X.; Hua, R. M. J. Agric. Food Chem. 2018, 66, 1023. |
| [17] | Neumann, D. M.; Cammarata, A.; Backes, G.; Palmer, G. E.; Jursic, B. S. Bioorg. Med. Chem. 2014, 22, 813. |
| [18] | Guo, H. Y.; Jin, C. M.; Zhang, H. M.; Jin, C.-M.; Shen, Q. K.; Quan, Z. S. J. Agric. Food Chem. 2019, 67, 9630. |
| [19] | Palwinder Singh, S. Eur. J. Med. Chem. 2014, 74, 440. |
| [20] | Singh, P.; Kaur, M.; Verma, P. Bioorg. Med. Chem. Lett. 2009, 19, 3054. |
| [21] | Siddiqui, Z. N.; Musthafa, T. N. M.; Ahmad, A.; Khan, A. U. Bioorg. Med. Chem. Lett. 2011, 21, 2860. |
| [22] | Yan, Q.; Cao, R. H.; Yi, W.; Chen, Z. Y.; Wen, H.; Ma, L.; Song, H. C. Eur. J. Med. Chem. 2009, 44, 4235. |
| [23] | Neumann, D. M.; Cammarata, A.; Backes, G.; Palmer, G. E.; Jursic, B. S. Bioorg. Med. Chem. 2014, 22, 813. |
| [24] | Gao, Y.; Xie, J. S.; Tang, R. T.; Yang, K. Y.; Zhang, Y. H.; Chen, L. X.; Li, H. Bioorg. Chem. 2019, 85, 168. |
| [25] | Laxmi, S. V.; Reddy, Y. T.; Kuarm, B. S.; Reddy, P. N.; Crooks, P. A.; Rajitha, B. Bioorg. Med. Chem. Lett. 2011, 21, 4329. |
| [26] | Freeman-Cook, K. D.; Reiter, L. A.; Noe, M. C.; Antipas, A. S.; Danley, D. E.; Datta, K.; Downs, J. T.; Eisenbeis, S.; Eskra, J. D.; Garmene, D. J.; Greer, E. M.; Griffiths, R. J.; Guzman, R.; Hardink, J. R.; Janat, F.; Jones, C. S.; Martinelli, G. J.; Mitchell, P. G.; Laird, E. R.; Liras, J. L.; Lopresti-Morrow, L. L.; Pandit, J.; Reilly, U. D.; Robertson, D.; Vaughn-Bowser, M. L.; Wolf-Gouviea, L. A.; Yocum, S. A. Bioorg. Med. Chem. Lett. 2007, 17, 6529. |
| [27] | Kim, S. H.; Pudzianowski, A. T.; Leavitt, K. J.; Barbosa, J.; McDonnell, P. A.; Metzler, W. J.; Rankin, B. M.; Liu, R.; Vaccaro, W.; Pitts, W. Bioorg. Med. Chem. Lett. 2005, 15, 1101. |
| [28] | Guerin, D. J.; Mazeas, D.; Musale, M. S.; Naguib, F. N. M.; Safarjalani, O. N. A.; Kouni, M. H.; Panzica, R. P. Bioorg. Med. Chem. Lett. 1999, 9, 1477. |
| [29] | Cordato, D. J.; Herkes, G. K.; Mather, L. E.; Morgan, M. K. J. Clin. Neurosci. 2003, 10, 283. |
| [30] | Willow, M.; Johnston, G. A. R. Int. Rev. Neurobiol. 1983, 24, 15. |
| [31] | Lee, D. L.; Carter, C. G. US 4797147A, 1989. |
| [32] | Lei, K.; Li, P.; Zhou, X. Y.; Wang, S. B.; Wang, X. K.; Ji, L. S.; Liu, R. M.; Xu, X. H. Chin. J. Org. Chem. 2020, 40, 2788. (in Chinese). |
| [32] | (雷康, 李攀, 周晓芸, 王世本, 王学堃, 冀卢莎, 柳仁民, 徐效华, 有机化学, 2020, 40, 2788.) |
| [33] | Lei, K.; Li, P.; Yang, X. F.; Wang, S. B.; Wang, X. K.; Hua, X.W. Sun, B.; Ji, L. S.; Xu, X. H. J. Agric. Food Chem. 2019, 67, 10489. |
| [34] | Lei, K.; Liu, Y.; Wang, S. B.; Sun, B.; Hua, X. W.; Xu, X. H. ; Chem. Res. Chin. Univ. 2019, 35, 609. |
| [35] | Li, N.; Fu, L. L.; Wang, S. B.; Liu, Y.; Lei, K.; Xu, X. H. J. Liaocheng Univ. (Nat. Sci. Ed.) 2018, 31, 53. (in Chinese). |
| [35] | (李娜, 付琳琳, 王世本, 刘洋, 雷康, 徐效华, 聊城大学学报(自然科学版), 2018, 31, 53.) |
| [36] | Lei, K.; Hua, X. W.; Tao, Y.-Y.; Liu, Y.; Liu, N.; Ma, Y.; Li, Y. H.; Xu, X. H.; Kong, C. H. Bioorg. Med. Chem. 2016, 24, 92. |
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