Citation: Qu Renyu, Yan Yaochao, Yang Jingfang, Chen Qiong, Yang Guangfu. Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2019, 39(8): 2303-2310. doi: 10.6023/cjoc201901043 shu

Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors

Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan 430079

Corresponding author: Chen Qiong, qchen@mail.ccnu.edu.cn Yang Guangfu, gfyang@mail.ccnu.edu.cn
Received Date: 26 January 2019
Revised Date: 4 March 2019
Available Online: 21 August 2019
Fund Project: the National Key Research and Development Program of China 2018YFD0200102the National Natural Science Foundation of China 21837001Project supported by the National Key Research and Development Program of China (No. 2018YFD0200102) and the National Natural Science Foundation of China (Nos. 21837001. 21772058)the National Natural Science Foundation of China 21772058

Figures(3)

Acetohydroxyacid synthase (AHAS) was one of important herbicidal targets. However, the issue of weed resistance to commercial AHAS inhibitors has become one of the largest obstacles for their application. Therefore, there is a high demand to design new anti-resistance AHAS inhibitors. Herein, based on the reported low resistance AHAS inhibitors, a series of pyrimidyl-salicylates with "double oxygen bridge" utilized the "conformation flexibility analysis" strategy were designed. All the synthesized compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. The bioactivity results showed that most of the derivatives displayed good inhibitory activities against P197L mutant. Especially, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluoro-4-nitrophenoxy)-4-methylbenzoic acid (6l) was identified as the most potent anti-resistance AHAS inhibitor. In addition, some compounds showed good weed control for resistant Descurainia sophia (P197L AHAS). Most importantly, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluorophenoxy)-4-methylbenzoic acid (6b) showed 80% herbicidal activities against sensitive and resistant Descurainia sophia at the dosage of 150 g ai/ha. These results indicated that this type of compounds worth of the further investigation.
- acetohydroxyacid synthase,
- anti-resistance,
- P197L mutant,
- conformation flexibility,
- resistant weed
1. [1]
  (a) Bar-Ilan, A.; Balan, V.; Tittmann, K.; Golbik, R.; Vyazmensky, M.; Huebner, G.; Barak, Z.; Chipman, D. M. Biochemistry 2001, 40, 11946.
  (b) Dug gleby, R. G.; Pang, S. S. J. Biochem. Mol. Biol. 2000, 33, 1.
2. [2]
  McCourt, J. A.; Pang, S. S.; King-Scott, J.; Guddat, L. W.; Duggleby, R. G.. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 569. doi: 10.1073/pnas.0508701103
3. [3]
  (a) Yu, Q.; Powles, S. B. Pest Manage. Sci. 2014, 70, 1340.
  (b) Tranel, P. J.; Wright, T. R. Weed Sci. 2002, 50, 700.
4. [4]
  Heap, I. The International Survey of Herbicide-Resistant Weeds, www.weedscience.org (accessed December 29, 2018).
5. [5]
  (a) Duggleby, R. G.; Pang, S. S.; Yu, H.; Guddat, L. W. Eur. J. Biochem. 2003, 270, 2895.
  (b) Hamouzova, K.; Kosnarova, P.; Salava, J.; Soukup, J.; Hamouz, P. Pest Manage. Sci. 2014, 70, 541.
  (c) Beckie, H. J.; Warwick, S. I.; Sauder, C. A.; Lozinski, C.; Shirriff, S. Weed Technol. 2011, 25, 170.
6. [6]
  (a) Legere, A.; Stevenson, F. C.; Beckie, H. J.; Warwick, S. I.; Johnson, E. N.; Hrynewich, B.; Lozinski, C. Weed Sci. 2013, 61, 267.
  (b) Intanon, S.; Perez-Jones, A.; Hulting, A. G.; Mallory-Smith, C. A. Weed Sci. 2011, 59, 431.
7. [7]
  Sibony, M.; Michel, A.; Haas, H. U.; Rubin, B.; Hurle, K. Weed Res. 2001, 41, 509. doi: 10.1046/j.1365-3180.2001.00254.x
8. [8]
  (a) Ji, F. Q.; Niu, C. W.; Chen, C. N.; Chen, Q.; Yang, G. F.; Xi, Z.; Zhan, C. G. ChemMedChem 2008, 3, 1203.
  (b) Liu, Y. C.; Qu, R. Y.; Chen, Q.; Yang, J. F.; Niu, C. W.; Zhen, X.; Yang, G. F. J. Agric. Food Chem. 2016, 64, 4845.
  (c) Qu, R. Y.; Yang, J. F.; Liu, Y. C.; Chen, Q.; Hao, G. F.; Niu, C. W.; Xi, Z.; Yang, G. F. Pest Manage. Sci. 2017, 73, 1373.
  (d) Qu, R. Y.; Yang, J. F.; Ponnam D.; Kang, W. M.; Liu, Y. C.; Chen, Q.; Niu, C. W.; Zhen, X.; Yang, G. F. J. Agric. Food Chem. 2017, 65, 11170.
9. [9]
  Li, K. J.; Qu, R. Y.; Liu, Y. C.; Yang, J. F.; Ponnam D.; Chen, Q.; Niu, C. W.; Zhen, X.; Yang, G. F. J. Agric. Food Chem. 2018, 66, 3773. doi: 10.1021/acs.jafc.8b00665
10. [10]
  Qu, R. Y.; Liu, Y. C.; Wu, Q. Y.; Chen, Q.; Yang, G. F. Tetrahedron 2015, 71, 8123. doi: 10.1016/j.tet.2015.08.040
11. [11]
  Chan, L.; McNally, A.; Toh, Q. Y.; Mendoza, A.; Gaunt, M. J. Chem. Sci. 2015, 6, 1277. doi: 10.1039/C4SC02856B
12. [12]
  Bolli, M. H.; Marfurt, J.; Grisostomi, C.; Boss, C.; Binkert, C.; Hess, P.; Treiber, A.; Thorin, E.; Morrison, K.; Buchmann, S.; Bur, D.; Ramuz, H.; Clozel, M.; Fischli, W.; Weller, T. J. Med. Chem. 2004, 47, 2776. doi: 10.1021/jm031115r
13. [13]
  Singh, B. K.; Stidham, M. A.; Shaner, D. L. Anal. Biochem. 1988, 171, 173. doi: 10.1016/0003-2697(88)90139-X
14. [14]
  Garcia, M. D.; Nouwens, A.; Lonhienne, T. G.; Guddat, L. W. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 1091. doi: 10.1073/pnas.1616142114
15. [15]
  Powell, M. J. D. Math. Program. 1977, 12, 241. doi: 10.1007/BF01593790
16. [16]
  Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Comput. Chem. 1998, 19, 1639. doi: 10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
17. [17]
  Cui, H. L.; Zhang, C. X.; Wei, S. H.; Zhang, H. J.; Li, X. J.; Zhang, Y. Q.; Wang, G. Q. Weed Sci. 2011, 59, 376. doi: 10.1614/WS-D-10-00099.1
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