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]
  Jianqiang Zheng , Yongbin Huang , Wencan Ming , Yingju Liu . Intelligent Reaction Optimization: Synthesis of Acetylsalicylic Acid Driven by Deep Learning and Optimization Algorithms. University Chemistry, 2025, 40(9): 87-98. doi: 10.12461/PKU.DXHX202411062
2. [2]
  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
3. [3]
  Jiaxi Xu , Yuan Ma . Stable Conformation of Several Common Aromatic Compounds. University Chemistry, 2025, 40(12): 183-186. doi: 10.12461/PKU.DXHX202508007
4. [4]
  Kexin Feng , Jie Zhang , Yujia Sun , Qiong Ai , Longchun Li . 乙酰二茂铁和二茂铁甲酰丙酮的合成、纯化及表征. University Chemistry, 2025, 40(8): 307-314. doi: 10.12461/PKU.DXHX202409045
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]
  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
7. [7]
  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
8. [8]
  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
9. [9]
  Shengdi Mao , Ruifeng Miao , Di Lan , Shijie Zhang , Jiguang Zhou , Xun Liu , Suxuan Du , Zhiwei Zhao , Guanglei Wu . Advances and challenges in flexible electromagnetic protection materials for electromagnetic interference shielding and wave absorption. Acta Physico-Chimica Sinica, 2026, 42(6): 100279-0. doi: 10.1016/j.actphy.2026.100279
10. [10]
  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
11. [11]
  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
12. [12]
  Yingtong FAN , Yujin YAO , Shouhao WAN , Yihang SHEN , Xiang GAO , Cuie ZHAO . Construction of copper tetrakis(4-carboxyphenyl)porphyrin/silver nanowire composite electrode for flexible and transparent supercapacitors. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1309-1317. doi: 10.11862/CJIC.20250043
13. [13]
  Qingtao CHEN , Xiangdong SHI , Xianghai RAO , Jiong LI , Xiaoyun QIN , Yiwen GUAN , Binyan ZOU , Guixia LIU , Fenghua CHEN . Employing polydopamine as an electron bridge to construct an S-scheme heterojunction and flexible film for highly efficient photocatalytic degradation of water pollutants. Chinese Journal of Inorganic Chemistry, 2026, 42(4): 747-759. doi: 10.11862/CJIC.20250286
14. [14]
  Xiaorong Ding , Aohan Hu , Siyu Zhang , Chongjiong Zheng , Long Su , Fei Lu . 聚丙烯酰胺凝胶电解质的制备及其在柔性水系锌离子电池中的应用. University Chemistry, 2026, 41(5): 391-397. doi: 10.12461/PKU.DXHX202511037
15. [15]
  Junlin Ma , Enze Wang , Haixia Wu . 柔性电化学传感器的制备及其在重金属离子现场便携检测中的应用. University Chemistry, 2026, 41(5): 455-468. doi: 10.12461/PKU.DXHX202509102
16. [16]
  Yu Shen , Ting Pan , Wenyong Lai . Construction and practice of an interdisciplinary innovative closed-loop talent cultivation model under the chemistry “101 plan”: a case study of integrating material chemistry with flexible electronics. University Chemistry, 2026, 41(6): 108-117. doi: 10.12461/PKU.DXHX202511208
17. [17]
  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
18. [18]
  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
19. [19]
  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
20. [20]
  Mengyang LI , Hao XU , Zhonghao NIU , Chunhua GONG , Weihui ZHONG , Jingli XIE . Highly effective catalytic synthesis of β-amino alcohols by using viologen-polyoxometalate hybrid materials. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1294-1300. doi: 10.11862/CJIC.20250080

Get Citation

PDF

XML

Metrics

PDF Downloads(12)
Abstract views(2210)
HTML views(340)

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