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
1. [1]
  Tengjiao Wang , Tian Cheng , Rongjun Liu , Zeyi Wang , Yuxuan Qiao , An Wang , Peng Li . Conductive Hydrogel-based Flexible Electronic System: Innovative Experimental Design in Flexible Electronics. University Chemistry, 2024, 39(4): 286-295. doi: 10.3866/PKU.DXHX202309094
2. [2]
  Lin Song , Dourong Wang , Biao Zhang . Innovative Experimental Design and Research on Preparing Flexible Perovskite Fluorescent Gels Using 3D Printing. University Chemistry, 2024, 39(7): 337-344. doi: 10.3866/PKU.DXHX202310107
3. [3]
  Qiaoqiao BAI , Anqi ZHOU , Xiaowei LI , Tang LIU , Song LIU . Construction of pressure-temperature dual-functional flexible sensors and applications in biomedicine. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2259-2274. doi: 10.11862/CJIC.20240128
4. [4]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
5. [5]
  Jiaxi Xu , Yuan Ma . Influence of Hyperconjugation on the Stability and Stable Conformation of Ethane, Hydrazine, and Hydrogen Peroxide. University Chemistry, 2024, 39(11): 374-377. doi: 10.3866/PKU.DXHX202402049
6. [6]
  Qingying Gao , Tao Luo , Jianyuan Su , Chaofan Yu , Jiazhu Li , Bingfei Yan , Wenzuo Li , Zhen Zhang , Yi Liu . Refinement and Expansion of the Classic Cinnamic Acid Synthesis Experiment. University Chemistry, 2024, 39(5): 243-250. doi: 10.3866/PKU.DXHX202311074
7. [7]
  Pingping Zhu , Yongjun Xie , Yuanping Yi , Yu Huang , Qiang Zhou , Shiyan Xiao , Haiyang Yang , Pingsheng He . Excavation and Extraction of Ideological and Political Elements for the Virtual Simulation Experiments at Molecular Level: Taking the Project “the Simulation and Computation of Conformation, Morphology and Dimensions of Polymer Chains” as an Example. University Chemistry, 2024, 39(2): 83-88. doi: 10.3866/PKU.DXHX202309063
8. [8]
  Li'na ZHONG , Jingling CHEN , Qinghua ZHAO . Synthesis of multi-responsive carbon quantum dots from green carbon sources for detection of iron ions and L-ascorbic acid. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 709-718. doi: 10.11862/CJIC.20240280
9. [9]
  Zhuoya WANG , Le HE , Zhiquan LIN , Yingxi WANG , Ling LI . Multifunctional nanozyme Prussian blue modified copper peroxide: Synthesis and photothermal enhanced catalytic therapy of self-provided hydrogen peroxide. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2445-2454. doi: 10.11862/CJIC.20240194
10. [10]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
11. [11]
  Yuan Zheng , Quan Lan , Zhenggen Zha , Lingling Li , Jun Jiang , Pingping Zhu . Teaching Reform of Organic Synthesis Experiments by Introducing Reverse Thinking and Design Concepts: Taking the Synthesis of Cinnamic Acid Based on Retrosynthetic Analysis as an Example. University Chemistry, 2024, 39(6): 207-213. doi: 10.3866/PKU.DXHX202310065
12. [12]
  Yukun Chang , Haoqin Huang , Baolei Wang . Preparation of Trans-Cinnamic Acid via “One-Pot” Protocol of Aldol Condensation-Hydrolysis Reaction: Recommending an Improved Organic Synthesis Experiment. University Chemistry, 2024, 39(4): 322-328. doi: 10.3866/PKU.DXHX202309095
13. [13]
  Lirui Shen , Kun Liu , Ying Yang , Dongwan Li , Wengui Chang . Synthesis and Application of Decanedioic Acid-N-Hydroxysuccinimide Ester: Exploration of Teaching Reform in Comprehensive Applied Chemistry Experiment. University Chemistry, 2024, 39(8): 212-220. doi: 10.3866/PKU.DXHX202312035
14. [14]
  Jinghua Wang , Yanxin Yu , Yanbiao Ren , Yesheng Wang . Integration of Science and Education: Investigation of Tributyl Citrate Synthesis under the Promotion of Hydrate Molten Salts for Research and Innovation Training. University Chemistry, 2024, 39(11): 232-240. doi: 10.3866/PKU.DXHX202402057
15. [15]
  Hong CAI , Jiewen WU , Jingyun LI , Lixian CHEN , Siqi XIAO , Dan LI . Synthesis of a zinc-cobalt bimetallic adenine metal-organic framework for the recognition of sulfur-containing amino acids. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 114-122. doi: 10.11862/CJIC.20240382
16. [16]
  Quanliang Chen , Zhaohui Zhou . Research on the Active Site of Nitrogenase over Fifty Years. University Chemistry, 2024, 39(7): 287-293. doi: 10.3866/PKU.DXHX202310133
17. [17]
  Ying Zhang , Fang Ge , Zhimin Luo . AI-Driven Biochemical Teaching Research: Predicting the Functional Effects of Gene Mutations. University Chemistry, 2025, 40(3): 277-284. doi: 10.12461/PKU.DXHX202412104
18. [18]
  Heng Zhang . Determination of All Rate Constants in the Enzyme Catalyzed Reactions Based on Michaelis-Menten Mechanism. University Chemistry, 2024, 39(4): 395-400. doi: 10.3866/PKU.DXHX202310047
19. [19]
  Lu XU , Chengyu ZHANG , Wenjuan JI , Haiying YANG , Yunlong FU . Zinc metal-organic framework with high-density free carboxyl oxygen functionalized pore walls for targeted electrochemical sensing of paracetamol. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 907-918. doi: 10.11862/CJIC.20230431
20. [20]
  Chunmei GUO , Weihan YIN , Jingyi SHI , Jianhang ZHAO , Ying CHEN , Quli FAN . Facile construction and peroxidase-like activity of single-atom platinum nanozyme. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1633-1639. doi: 10.11862/CJIC.20240162

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(1036)
HTML views(129)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142