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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 9: 2788 - 2797

DOI: https://doi.org/10.6023/cjoc202005031

Design, Synthesis and Herbicidal Activity of 5-Acylbarbituric Acid Derivatives and Study of Molecular Mode of Action

  • Lei Kang ,
  • Li Pan ,
  • Zhou Xiaoyun ,
  • Wang Shiben ,
  • Wang Xuekun ,
  • Ji Lusha ,
  • Liu Renmin ,
  • Xu Xiaohua
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  • a School of Pharmacy, Liaocheng University, Liaocheng, Shandong 252000;
    b State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071

Received date: 2020-05-13

  Revised date: 2020-06-15

  Online published: 2020-07-09

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 31701827, 81803360), the China Postdoctoral Science Foundation (No. 2020M671984), the Doctoral Research Startup Foundation of Liaocheng University (No. 318051647), the Innovation and Entrepreneurship Training Program for College Students of Liaocheng University (No. CXCY2020Y179) and the Natural Science Foundation of Shandong Province (Nos. ZR2019PC041, ZR2017BH037).

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Abstract

In an effort to develop novel β-triketone herbicides containing a barbituric acid moiety, a series of 5-acylbarbituric acid derivatives were designed, synthesized, and tested for herbicidal activity. The bioassay results showed that some of the target compounds, such as 5-(2-(2-chloro-4-fluorophenoxy)-1-hydroxyethylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (BBA-22) and 5-(2-(2-bromo-4-fluorophenoxy)-1-hydroxyethylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (BBA-27), exhibited excellent herbicidal activity against all tested weeds at a dosage of 1500 g·ha-1. In particular, compound BBA-22 displayed good pre-emergent herbicidal activity against Brassica campestris, Amaranthus retroflexus and Digitaria sanguinalis even at a dosage of 187.5 g·ha-1,surpassing that of a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Investigation of the molecular mode of action of compound BBA-22 upon treatment of Arabidopsis thaliana as a model plant revealed that BBA-22 was degraded to the corresponding phenoxyacetic acid, which explains why the herbicidal mechanism is similar to that of auxin-type herbicides. The present study demonstrates that compound BBA-22 is a proherbicide of the corresponding phenoxyacetic acid auxin herbicide and a potential lead compound for further development of novel auxin herbicides.

Key words： β-triketone; 5-acylbarbituric acid; synthesis; herbicide; phenoxyacetic

Cite this article

Lei Kang , Li Pan , Zhou Xiaoyun , Wang Shiben , Wang Xuekun , Ji Lusha , Liu Renmin , Xu Xiaohua . Design, Synthesis and Herbicidal Activity of 5-Acylbarbituric Acid Derivatives and Study of Molecular Mode of Action[J]. Chinese Journal of Organic Chemistry, 2020 , 40(9) : 2788 -2797 . DOI: 10.6023/cjoc202005031

References

[1] Dumas, E.; Giraudo, M.; Goujon, E.; Halma, M.; Knhili, E.; Stauffert, M.; Batisson, I.; Besse-Hoggan, P.; Bohatier, J.; Bouchard, P.; Celle-Jeanton, H.; Costa Gomes, M.; Delbac, F.; Forano, C.; Goupil, P.; Guix, N.; Husson, P.; Ledoigt, G.; Sarraute, S. J. Hazrd. Mater. 2017, 325, 136.
[2] Park, C. G.; Jang, M.; Shin, E.; Kim, J. Molecules 2017, 22, 1050.
[3] Li, X. C.; Ferreira, D.; Jacob, M. R.; Zhang, Q. F.; Khan, S. I.; ElSohly, H. N.; Nagle, D. G.; Smillie, T. J.; Khan, I. A.; Walker, L. A.; Clark, A. M. J. Am. Chem. Soc. 2004, 126, 6872.
[4] Wu, J. W.; Li, B. L.; Tang, C.; Ke, C. Q.; Zhu, N. L.; Qiu, S. X.; Ye, Y. J. Nat. Prod. 2019, 82, 1917.
[5] Song, J. G.; Su, J. C.; Song, Q. Y.; Huang, R. L.; Tang, W.; Hu, L. J.; Huang, X. J.; Jiang, R. W.; Li, Y. L.; Ye, W. C.; Wang, Y. Org. Lett. 2019, 21, 9579.
[6] Qin, X. J.; Liu, H.; Yu, Q.; Yan, H.; Tang, J. F.; An, L. K.; Khan, A.; Chen, Q. R.; Hao, X. J.; Liu, H. Y. Tetrahedron 2017, 73, 1803.
[7] Carroll, A. R.; Avery, V. M.; Duffy, S.; Forsterd, P. I.; Guymerd, G. P. Org. Biomol. Chem. 2013, 11, 453.
[8] Hellyer, R. O. Aust. J. Chem. 1968, 21, 2825.
[9] Killeen, D. P.; Larsen, L.; Dayan, F. E.; Gordon, K. C.; Perry, N. B.; van Klink, J. W. J. Nat. Prod. 2016, 79, 564.
[10] Igarashi, M.; Tetsuka, Y.; Mimura, Y.; Takahashi, A.; Tamamura, T.; Sato, K. J. Antibiot. 1993, 46, 1843.
[11] Kong, L. Y.; Cui, Q.; Jin, Z.; Xu, X. H. Tetrahedron Lett. 2018, 59, 1705.
[12] Tagasgira, M.; Watanabe, M.; Uemitsu, N. Biosci., Biotechnol.. Biochem. 1995, 59, 740.
[13] Senadeera, S. P. D.; Lucantoni, L.; Duffy, S.; Avery, V. M.; Carroll, A. R. J. Nat. Prod. 2018, 81, 1588.
[14] Wang, S. Y.; Lan, X. Y.; Xiao, J. H.; Yang, J. C.; Kao, Y. T.; Chang, S. T. Phytother. Res. 2008, 22, 213.
[15] Christoph, F.; Kaulfers, P. M.; Stahl-Biskup, E. Planta Med. 2001, 67, 768.
[16] van Klink, J. W.; Larsen, L.; Perry, N. B.; Weavers, R. T.; Cook, G. M. Bremer, P. J. Bioorg. Med. Chem. 2005, 13, 6651.
[17] Cacic, M.; Trkovnik, M.; Cacic, F.; Has-Schon, E. Molecules 2006, 11, 134.
[18] Beaudegnies, R.; Edmunds, A. J. F.; Fraser, T. E. M.; Hall, R. G.; Hawkes, T. R.; Mitchell, G.; Schaetzer, J.; Wendeborn, S.; Wibley, J. Bioorg. Med. Chem. 2009, 17, 4134.
[19] Lv, P.; Chen, Y.; Zhao, Z.; Shi, T.; Wu, X.; Xue, J.; Li, Q. X.; Hua, R. J. Agric. Food Chem. 2018, 66, 1023.
[20] Lei, K.; Sun, D.W.; Hua, X. W.; Tao, Y. Y.; Xu, X. H.; Kong, C. H. Pest Manage. Sci. 2016, 72, 1381.
[21] Shestak, O. P.; Novikov, V. L.; Martyyas, E. A.; Anisimov, M. M. Pharm. Chem. J. 2009, 43, 498.
[22] Gilardoni, G.; Clericuzio, M.; Tosi, S.; Zanoni, G.; Vidari, G. J. Nat. Prod. 2007, 70, 137.
[23] Christoph, F.; Kaulfers, P. M.; Stahl-Biskup, E. Planta Med. 2000, 66, 556.
[24] Khambay, B. P. S.; Beddie, D. G.; Hooper, A. M.; Simmonds, M. S. J. Tetrahedron 2003, 59, 7131.
[25] Li, H. B.; Li, L.; Li, J. X.; Han, T. F.; He, J. L.; Zhu, Y. Q. Pest Manage. Sci. 2018, 74, 579.
[26] Wang, D. W.; Lin, H. Y.; He, B.; Wu, F. X.; Chen, T.; Chen, Q.; Yang, W. C.; Yang, G. F. J. Agric. Food Chem. 2016, 64, 8986.
[27] Wang, D. W.; Lin, H. Y.; Cao, R. J.; Ming, Z. Z.; Chen, T.; Hao, G. F.; Yang, W. C.; Yang, G. F. Pest Manage. Sci. 2015, 71, 1122.
[28] Wang, D. W.; Lin, H. Y.; Cao, R. J.; Chen, T.; Wu, F. X.; Hao, G. F.; Chen, Q.; Yang, W. C.; Yang, G. F. J. Agric. Food Chem. 2015, 63, 5587.
[29] Wang, D. W.; Lin, H. Y.; Cao, R. J.; Yang, S. G.; Chen, Q.; Hao, G. F.; Yang, W. C.; Yang, G. F. J. Agric. Food Chem. 2014, 62, 11786.
[30] Palwinder Singh, S. Eur. J. Med. Chem. 2014, 74, 440.
[31] Singh, P.; Kaur, M.; Verma, P. Bioorg. Med. Chem. Lett. 2009, 19, 3054.
[32] Siddiqui, Z. N.; Musthafa, T. N. M.; Ahmad, A.; Khan, A. U. Bioorg. Med. Chem. Lett. 2011, 21, 2860.
[33] Yan, Q.; Cao, R. H.; Yi, W.; Chen, Z. Y.; Wen, H.; Ma, L.; Song, H. C. Eur. J. Med. Chem. 2009, 44, 4235.
[34] Neumann, D. M.; Cammarata, A.; Backes, G.; Palmer, G. E.; Jursic, B. S. Bioorg. Med. Chem. 2014, 22, 813.
[35] Gao, Y.; Xie, J. S.; Tang, R. T.; Yang, K. Y.; Zhang, Y. H.; Chen, L. X.; Li, H. Bioorg. Chem. 2019, 85, 168.
[36] Laxmi, S. V.; Reddy, Y. T.; Kuarm, B. S.; Reddy, P. N.; Crooks, P. A.; Rajitha, B. Bioorg. Med. Chem. Lett. 2011, 21, 4329.
[37] 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.; Mitchella, P. G.; Yocuma, S. A. Bioorg. Med. Chem. Lett. 2007, 17, 6529.
[38] 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.
[39] Cordato, D. J.; Herkes, G. K.; Mather, L. E.; Morgan, M. K. J. Clin. Neurosci. 2003, 10, 283.
[40] Willow, M.; Johnston, G. A. R. Int. Rev. Neurobiol. 1983, 24, 15.
[41] Reddy, Y. T.; Sekhar, K. R.; Sasi, N.; Reddy, P. N.; Freeman, M. L.; Crooks, P. A. Bioorg. Med. Chem. Lett. 2010, 20, 600.
[42] Altowyan, M. S.; Barakat, A.; Soliman, S. M.; Al-Majid, A. M.; Ali, M.; Elshaier, Y. A. M. M.; Ghabbour, H. A. J. Mol. Struct. 2019, 1175, 524.
[43] Haldar, M. K.; Scott, M. D.; Sule, N.; Srivastavab, D. K.; Mallik, S. Bioorg. Med. Chem. Lett. 2008, 18, 2373.
[44] 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.
[45] Lee, D. L.; Carter, C. G. US4797147, 1989.
[46] 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.
[47] Lei, K.; Liu, Y.; Wang, S. B.; Sun, B.; Hua, X. W.; Xu, X. H. Chem. Res. Chin. Univ. 2019, 35, 609.
[48] 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). (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.)
[49] Xu, C.; Zhang, Y.; Yu, Y.; Li, Y.; Wei, S. Bioelectromagnetics 2018, 39, 15.
[50] Song, Y. J. Integr. Plant Biol. 2014, 56, 106.
[51] Scherer, G. F. E.; Zahn, M.; Callis, J.; Jones, A. M. FEBS Lett. 2007, 581, 4205.
[52] Raghavan, C.; Ong, E. K.; Dalling, M. J.; Stevenson, T. W. Funct. Integr. Genomics 2006, 6, 60.
[53] Bayramoğlu, D.; Kurtay, G.; Güllü, M. Synth. Commun. 2020, 50, 649.
[54] Thinnes, C. C.; Lohans, C. T.; Abboud, M. I.; Yeh, T. L.; Tumber, A.; Nowak, R. P.; Attwood, M.; Cockman, M. E.; Oppermann, U.; Loenarz, C.; Schofield, C. J. Chem. Eur. J. 2019, 25, 2019.
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