Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors

doi:10.6023/cjoc201901043

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (8): 2303-2310.DOI: 10.6023/cjoc201901043 Previous Articles Next Articles

Articles

新型嘧啶-水杨酸类抑制剂的设计、合成及其生物活性研究

曲仁渝, 严耀超, 杨景芳, 陈琼, 杨光富

华中师范大学化学学院农药与化学生物学教育部重点实验室武汉 430079

收稿日期:2019-01-26 修回日期:2019-03-04 发布日期:2019-03-21
通讯作者: 陈琼, 杨光富 E-mail:gfyang@mail.ccnu.edu.cn;qchen@mail.ccnu.edu.cn
基金资助:
国家重点研发计划（No.2018YFD0200102）、国家自然科学基金（Nos.21837001.21772058）资助项目.

Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors

Qu Renyu, Yan Yaochao, Yang Jingfang, Chen Qiong, Yang Guangfu

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

Received:2019-01-26 Revised:2019-03-04 Published:2019-03-21
Contact: 10.6023/cjoc201901043 E-mail:gfyang@mail.ccnu.edu.cn;qchen@mail.ccnu.edu.cn
Supported by:
Project supported by the National Key Research and Development Program of China (No. 2018YFD0200102) and the National Natural Science Foundation of China (Nos. 21837001. 21772058).

1. Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors.PDF(835KB)

Abstract

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.

Key words: acetohydroxyacid synthase, anti-resistance, P197L mutant, conformation flexibility, resistant weed

Cite this article

Qu Renyu, Yan Yaochao, Yang Jingfang, Chen Qiong, Yang Guangfu. Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors[J]. Chin. J. Org. Chem., 2019, 39(8): 2303-2310.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[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] 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.
[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] Heap, I. The International Survey of Herbicide-Resistant Weeds, www. weedscience. org (accessed December 29, 2018).
[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] (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] Sibony, M.; Michel, A.; Haas, H. U.; Rubin, B.; Hurle, K. Weed Res. 2001, 41, 509.
[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] 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.
[10] Qu, R. Y.; Liu, Y. C.; Wu, Q. Y.; Chen, Q.; Yang, G. F. Tetrahedron 2015, 71, 8123.
[11] Chan, L.; McNally, A.; Toh, Q. Y.; Mendoza, A.; Gaunt, M. J. Chem. Sci. 2015, 6, 1277.
[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.
[13] Singh, B. K.; Stidham, M. A.; Shaner, D. L. Anal. Biochem. 1988, 171, 173.
[14] Garcia, M. D.; Nouwens, A.; Lonhienne, T. G.; Guddat, L. W. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 1091.
[15] Powell, M. J. D. Math. Program. 1977, 12, 241.
[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.
[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.

新型嘧啶-水杨酸类抑制剂的设计、合成及其生物活性研究

Design, Synthesis and Bioactivity of New Pyrimidyl-salicylate Inhibitors

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 1

Recommended Articles

Metrics

Comments