新型苯并噻唑-嘧啶二酮类化合物的设计、合成与除草活性研究

doi:10.6023/cjoc202311025

摘要/Abstract

基于课题组前期研究发现的苯并噻唑-嘧啶二酮衍生物, 以氧桥替换硫桥的策略, 设计并合成了一系列未见文献报道的以苯并噻唑为骨架的新型嘧啶二酮类衍生物. 测试了所有化合物在150 g a.i./ha剂量下的温室盆栽除草活性, 结果表明部分化合物对所测试的6种杂草具有较好的除草活性, 特别是2-((6-氟-5-(3-甲基-2,6-二氧亚基-4-(三氟甲基)-3,6-二氢嘧啶-1(2H)-基)苯并[d]噻唑-2-基)氧)乙酸乙酯(9ac), 对供试杂草均具有85%以上的防效, 表现出广谱的除草活性.

关键词: 原卟啉原氧化酶(PPO)抑制剂, 苯并噻唑, 嘧啶二酮, 除草活性, 分子对接

Based on the benzothiazole-pyrimidinedione derivatives discovered in the our previous report, a series of novel pyrimidinedione derivatives with benzothiazole as the scaffold, which have not been reported in the literature, were designed and synthesized by the strategy of replacing sulfur bridge with oxygen bridge. All of the target compounds were evaluated for their herbicidal activity in the greenhouse assay at a dose of 150 g a.i./ha, and the results showed that some compounds exhibited good herbicidal activity against the tested six weeds. In particular, ethyl 2-((6-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro- methyl)-3,6-dihydropyrimidin-1(2H)-yl)benzo[d]thiazol-2-yl)oxy)acetate (9ac) showed a broad-spectrum herbicidal activity with more than 85% efficacy against the weeds tested.

Key words: protoporphyrinogen oxidase (PPO) inhibitors, benzothiazole, pyrimidinedione, herbicidal activity, molecular docking

引用此文

郑佰峰, 左炀, 陈琼, 吴琼友. 新型苯并噻唑-嘧啶二酮类化合物的设计、合成与除草活性研究[J]. 有机化学, 2024, 44(7): 2371-2376.

Baifeng Zheng, Yang Zuo, Qiong Chen, Qiongyou Wu. Design, Synthesis and Herbicidal Activity of Novel Benzothiazole-Pyrimidinediones Compounds[J]. Chinese Journal of Organic Chemistry, 2024, 44(7): 2371-2376.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 5

图1. 代表性的商品化PPO抑制剂类除草剂

Figure 1. Representative commercial PPO-inhibiting herbicides

图2. 目标化合物的设计

Figure 2. Molecular design of target compounds

图式1. 苯并噻唑-嘧啶二酮类化合物的合成路线

Scheme 1. Synthetic routes of benzothiazole-pyrimidinedione compounds

Compd.	X	R	苗后除草活性(150 g a.i./ha)
Compd.	X	R	棒头草	菵草	早熟禾	芥菜	小藜	繁缕
9aa	F	CH₃	100	80	80	100	100	100
9ab	F	CH₂CH₃	100	85	80	100	100	100
9ac	F	CH₂COOCH₂CH₃	100	85	90	100	100	100
9ad	F	CH₂COO(CH₂)₃CH₃	60	70	80	100	100	100
9ba	Cl	CH₃	60	60	60	95	95	70
9bb	Cl	CH₂CH₃	40	0	0	50	90	0
9bc	Cl	CH₂COOCH₂CH₃	60	0	0	70	100	0
9bd	Cl	CH(CH₃)COOCH₃	60	0	50	85	85	0
9be	Cl	CH(CH₃)COOCH₂CH₃	60	0	0	75	95	0
9bf	Cl	CH₂COO(CH₂)₃CH₃	30	0	50	75	95	50
9ca	Br	CH₂COOCH₂CH₃	0	0	0	0	85	0
9cb	Br	CH(CH₃)COOCH₃	60	0	0	70	90	0
9cc	Br	CH(CH₃)COOCH₂CH₃	0	0	0	0	85	0
9cd	Br	CH₂COO(CH₂)₃CH₃	0	0	0	0	85	0
噁草酮			90	80	90	90	100	100

表1. 目标化合物的温室除草活性(抑制剂/%)

Table 1. Herbicidal activity of title compounds in greenhouse (inhibition rate/%)

图3. 化合物1 (品红色)和9ac (浅蓝色)在NtPPO空腔中的结合模式叠加图

Figure 3. Superposition of binding modes of compound 1 (pink sticks) and 9ac (light blue sticks) in NtPPO The key residues in the binding pocket are shown in light gray sticks. Hydrogen bond are shown in red dashed line. Tthe hydrogen bond distances of compounds 1-Arg98 and 9ac-Arg98 are 0.41 and 0.39 nm, respectively.

参考文献 21

[1]	Wang, D. W.; Zhang, H.; Yu, S. Y.; Zhang, R. B.; Liang, L.; Wang, X.; Yang, H. Z.; Xi, Z. J. Agric. Food Chem. 2021, 69, 14115.
[2]	Zhang, R. B.; Yu, S. Y.; Liang, L.; Ismail, I.; Wang, D. W.; Li, Y. H.; Xu, H.; Wen, X.; Xi, Z. J. Agric. Food Chem. 2020, 68, 13672.
[3]	Zheng, B. F.; Wang, Z. Z.; Dong, J.; Ma, J. Y.; Zuo, Y.; Wu, Q. Y.; Yang, G. F. J. Agric. Food Chem. 2023, 71, 8746.
[4]	Dayan, F. E.; Barker, A.; Tranel, P. J. Pest Manage. Sci. 2018, 74, 2226.
[5]	Zheng, B. F.; Zuo, Y.; Huang, G. Y.; Wang, Z. Z.; Ma, J. Y.; Wu, Q. Y.; Yang, G. F. J. Agric. Food Chem. 2023, 71, 14221.
[6]	Hao, G. F.; Tan, Y.; Xu, W. F.; Cao, R. J.; Xi, Z.; Yang, G. F. J. Agric. Food Chem. 2014, 62, 7209.
[7]	Brzezowski, P.; Ksas, B.; Havaux, M.; Grimm, B.; Chazaux, M.; Peltier, G.; Johnson, X.; Alric, J. Commun. Biol. 2019, 2, 159. doi: 10.1038/s42003-019-0395-5 pmid: 31924988
[8]	Hao, G. F.; Zhan, C. G.; Yang, G. F. Future Med. Chem. 2014, 6, 597.
[9]	Wu, Q. Y.; Jiang, L. L.; Zuo, Y.; Wang, Z. F.; Xi, Z.; Yang, G. F. Chem. Biol. Drug Des. 2014, 84, 431.
[10]	Zheng, B. F.; Zuo, Y.; Yang, W. Y.; Liu, H.; Wu, Q. Y.; Yang, G. F. J. Agric. Food. Chem. 2024, 72, 10772.
[11]	Zhao, L. X.; Peng, J. F.; Liu, F. Y.; Zou, Y. L.; Gao, S.; Fu, Y.; Ye, F. J. Agric. Food Chem. 2022, 70, 1003.
[12]	Hao, G. F.; Zuo, Y.; Yang, S. G.; Yang, G. F. Chimia (Aarau) 2011, 65, 961.
[13]	Zheng, B. F.; Yan, Y. C.; Fu, C.; Huang, G. Y.; Zhao, L.; Chen, Q.; Qu, R. Y.; Yang, G. F. Front. Agric. Sci. Eng. 2022, 9, 133.
[14]	Duke, S. O.; Dayan, F. E. Pest Manage. Sci. 2022, 78, 1303.
[15]	Wang, D. W.; Liang, L.; Xue, Z. Y.; Yu, S. Y.; Zhang, R. B.; Wang, X.; Xu, H.; Wen, X.; Xi, Z. J. Agric. Food Chem. 2021, 69, 4081.
[16]	Wang, D. W.; Zhang, R. B.; Yu, S. Y.; Liang, L.; Ismail, I.; Li, Y. H.; Xu, H.; Wen, X.; Xi, Z. J. Agric. Food Chem. 2019, 67, 12382.
[17]	Lee, W. H.; Kwon, Y. B.; Kim, J. H.; Lee, K. H.; Maezono, S. M. B.; Choi, J. S.; Seu, Y. B. Bioorg. Med. Chem. 2021, 31, 115959.
[18]	Wang, D. W.; Zhang, R. B.; Ismail, I.; Xue, Z. Y.; Liang, L.; Yu, S. Y.; Wen, X.; Xi, Z. J. Agric. Food Chem. 2019, 67, 9254.
[19]	Zuo, Y.; Wu, Q. Y.; Su, S. W.; Niu, C. W.; Xi, Z.; Yang, G. F. J. Agric. Food Chem. 2016, 64, 552.
[20]	Yang, G. F. Adv. Agrochem, 2022, 1, 85.
[21]	Hao, G. F.; Zuo, Y.; Yang, S. G.; Chen, Q.; Zhang, Y.; Yin, C. Y.; Niu, C. W.; Xi, Z.; Yang, G. F. J. Agric. Food Chem. 2017, 65, 5581.