含天然苯乙烯结构的4-甲基-1,2,4-三唑-硫醚化合物的合成、除草活性及三维定量构效关系(3D-QSAR)研究

doi:10.6023/cjoc202011023

摘要/Abstract

为了寻找以天然可再生资源为基础的除草剂, 设计并合成了26个新型含天然苯乙烯结构的4-甲基-1,2,4-三唑-硫醚类化合物, 并通过FTIR,¹H NMR, ¹³C NMR, ESI-MS和元素分析等方法对其结构进行了确认. 初步的除草活性测试表明, 在质量浓度为100 µg/mL时, 大多数目标化合物对油菜胚根生长表现出良好的抑制活性, 其中8个化合物的抑制率超过81.4%, 远优于阳性对照丙炔氟草胺(抑制率63.0%); 2个化合物对稗草幼苗生长有良好的抑制活性. 比较发现, R为脂肪族取代基或吡啶环对除草活性有利. 此外, 利用CoMFA方法对R为芳族取代基的目标化合物的油菜胚根抑制活性进行了初步的三维定量构效关系(3D-QSAR)研究, 建立了合理有效的3D-QSAR模型( r²=0.996, q²=0.603).

关键词: 苯乙烯, 肉桂醛, 1,2,4-三唑硫醚, 除草活性, 三维定量构效关系(3D-QSAR)

In an attempt to search for natural renewable resource-based herbicidal agents, twenty-six novel 4-methyl-1,2,4- triazole-thioether compounds containing natural styrene structure were designed and synthesized. Their structures were confirmed by FTIR,¹H NMR, ¹³C NMR, ESI-MS and elemental analysis. The preliminary herbicidal activity test showed that, at 100 µg/mL, most of the compounds showed good inhibitory activity against the root-growth of rape ( Brassica campestris), in which 8 compounds had inhibition rate of greater than 81.4%, implying much better herbicidal activity than that of the positive control flumioxazin with inhibition rate of 63.0%. Also, 2 compounds exhibited good inhibitory activity against the seedling-growth of barnyardgrass (Echinochloa crusgalli). It was found by comparison that aliphatic R substituents or pyridine rings were beneficial to herbicidal activity. Furthermore, a preliminary three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out by the CoMFA method for the inhibitory activity of the target compounds with aromatic R substituents against the root-growth of rape, and a reasonable and effective 3D-QSAR model (r²=0.996, q²=0.603) has been established.

Key words: styrene, cinnamaldehyde, 1,2,4-triazole-thioether, herbicidal activity, three-dimensional quantitative structure- activity relationship (3D-QSAR)

引用此文

李成飞, 岑波, 段文贵, 林桂汕, 王秀, 李宝谕. 含天然苯乙烯结构的4-甲基-1,2,4-三唑-硫醚化合物的合成、除草活性及三维定量构效关系(3D-QSAR)研究[J]. 有机化学, 2021, 41(6): 2485-2495.

Chengfei Li, Bo Cen, Wengui Duan, Guishan Lin, Xiu Wang, Baoyu Li. Synthesis, Herbicidal Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of 4-Methyl- 1,2,4-triazole-thioether Compounds Containing Natural Styrene Structure[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2485-2495.

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参考文献 45

[1]	Yang, L.; Zhou, L. Z.; Chen, H. Y.; Gu, Y. Farm. Prod. Process 2019, 2,41(in Chinese).
	( 杨漓, 周丽珠, 陈海燕, 谷瑶, 农产品加工, 2019, 2,41. )
[2]	Wu, C. H.; Shu, M.; Li, Q.; Ding, P. Chin. Med. J. Res. Prac. 2017, 31,14(in Chinese).
	( 伍彩红, 舒眉, 李倩, 丁平, 现代中药研究与实践, 2017, 31,14.)
[3]	Li, Q. Z.; Song, B. A.; Cai, X. J.; Zheng, Y. G.; Guo, Q. Q. Chin. J. Org. Chem. 2010, 30,569(in Chinese).
	( 李黔柱, 宋宝安, 蔡学建, 郑玉国, 郭晴晴, 有机化学, 2010, 30,569.)
[4]	Zhang, X. B.; Ma, H. Y.; Sun, T. D.; Lei, P.; Yang, X. L.; Zhang, X. M.; Ling, Y. Chin. J. Org. Chem. 2019, 39,2965(in Chinese). doi: 10.6023/cjoc201903031
	( 张学博, 马航宇, 孙腾达, 雷鹏, 杨新玲, 张晓鸣, 凌云, 有机化学, 2019, 39,2965.) doi: 10.6023/cjoc201903031
[5]	Marona, H.; Szkaradek, N.; Karczewska, E.; Trojanowska, D.; Budak, A.; Bober, P.; Przepiorka, W.; Marek Cegla, M.; Szneler, E. Arch. Pharm. Chem. Life Sci. 2010, 342,9. doi: 10.1002/ardp.v342:1
[6]	Xu, Y.; Lei, P.; Ling, Y.; Wang, S. W.; Yang, X. L. Chin. J. Org. Chem. 2014, 34,1118(in Chinese). doi: 10.6023/cjoc201401034
	( 徐焱, 雷鹏, 凌云, 王圣文, 杨新玲, 有机化学, 2014, 34,1118.) doi: 10.6023/cjoc201401034
[7]	Friedman, M. J. Agric. Food Chem. 2017, 65,10406. doi: 10.1021/acs.jafc.7b04344
[8]	Li, X.; sheng, J. Z.; Huang, G. H.; Ma, R. X.; Yin, F. X.; Song, D.; Zhao, C.; Ma, S. T. Eur. J. Med. Chem. 2015, 97,32. doi: 10.1016/j.ejmech.2015.04.048
[9]	Kim, H. K.; Kim, J. R.; Ahn, Y. J. J. Stored. Prod. Res. 2004, 40,55. doi: 10.1016/S0022-474X(02)00075-9
[10]	Saad, M. M. G.; Gouda, N. A. A.; Abdelgaleil, S. A. M. J. Environ. Sci. Heal. B 2019, 54,954. doi: 10.1080/03601234.2019.1653121
[11]	Chotsaeng, N.; Laosinwattana, C.; Charoenying, P. Molecules 2018, 23,471. doi: 10.3390/molecules23020471
[12]	Muñoz, M.; Torres‐Pagán, N.; Peiró, R.; Guijarro, R.; Sánchez‐Moreiras, A. M.; Verdeguer, M. Agronomy 2020, 10,791. doi: 10.3390/agronomy10060791
[13]	Zhou, J.; Yuan, X. R.; Li, L.; Zhang, T.; Wang, B. Nat. Prod. Res. 2017, 31,2909. doi: 10.1080/14786419.2017.1299724
[14]	Kwon, B. M.; Lee, S. H.; Choi, S. U.; Park, S. H.; lee, C. O.; Cho, Y. K.; Sung, N. D.; Bok, S. H. Arch. Pharm. Res. 1998, 21,147. pmid: 9875422
[15]	Ka, H.; Park, H. J.; Jung, H. J.; Choi, J. W.; Cho, K. S.; Ha, J.; Lee, K. T. Cancer Lett. 2003, 196,143. doi: 10.1016/S0304-3835(03)00238-6
[16]	Cabello, C. M.; 3rd, W. B. B.; Lamore, S. D.; Ley, S.; Bause, A. S.; Azimian, S.; Wondrak, G.T.. Free Radic. Biol. Med. 2009, 46,220. doi: 10.1016/j.freeradbiomed.2008.10.025
[17]	Wu, W. N.; Jiang, Y. M.; Zhang, B. Y.; Wang, J. Z.; Du, H. T.; Fei, Q. Chemistry 2019, 82,1115(in Chinese).
	( 吴文能, 姜阳明, 张卜艳, 王家忠, 杜海堂, 费强, 化学通报, 2019, 82,1115.)
[18]	He, S. C.; Zhang, H. Z.; Zhang, H. J.; Sun, Q.; Zhou, C. H. Med. Chem. 2020, 16,104. doi: 10.2174/1573406414666181106124852
[19]	Liu, X. H.; Sun, Z. H.; Yang, M. Y.; Tan, C. X.; Weng, J. Q.; Zhang, Y. G.; Ma, Y. Chem. Biol. Drug Des. 2014, 84,342. doi: 10.1111/cbdd.2014.84.issue-3
[20]	Rode, N. D.; Sonawane, A. D.; Nawale, L.; Khedkar, V. M.; Joshi, R. A.; Likhite, A. P.; Sarkar, D.; Joshi, R. R. Chem. Biol. Drug Des. 2017, 90,1206. doi: 10.1111/cbdd.2017.90.issue-6
[21]	Gilandoust, M.; Harsha, K. B.; Mohan, C. D.; Raquib, A. R.; Rangappa, S.; Pandey, V.; Lobie, P. E.; Basappa ; Rangappa, K. S.. Bioorg. Med. Chem. Lett. 2018, 28,2314. doi: S0960-894X(18)30420-7 pmid: 29789259
[22]	Korcz, M.; Saczewski, F.; Bednarski, P. J.; Kornicka, A. Molecules 2018, 23,1497. doi: 10.3390/molecules23061497
[23]	Massari, S.; Nannetti, G.; Desantis, J.; Muratore, G.; Sabatini, S.; Manfroni, G.; Mercorelli, B.; Cecchetti, V.; Palu, G.; Cruciani, G.; Loregian, A.; Goracci, L.; Tabarrini, O. J. Med. Chem. 2015, 58,3830. doi: 10.1021/acs.jmedchem.5b00012 pmid: 25856229
[24]	Liu, X. H.; Xu, X. Y.; Tan, C. X.; Weng, J. Q.; Xin, J. H.; Chen, J. Pest Manage. Sci. 2015, 71,292. doi: 10.1002/ps.3804
[25]	Wang, B. L.; Zhang, L. Y.; Liu, X. H.; Ma, Y.; Zhang, Y.; Li, Z. M.; Zhang, X. Bioorg. Med. Chem. Lett. 2017, 27,5457. doi: 10.1016/j.bmcl.2017.10.065
[26]	Wang, B. L.; Zhang, L. Y.; Zhan, Y. Z.; Zhang, Y.; Zhang, X.; Wang, L. Z.; Li, Z. M. J. Fluorine Chem. 2016, 184,36. doi: 10.1016/j.jfluchem.2016.02.004
[27]	Xu, W. M.; Song, B. A.; Yang, S.; Hu, D. Y.; Zeng, S. Agrochemicals 2010, 49,625(in Chinese).
	( 徐维明, 宋宝安, 杨松, 胡德禹, 曾松, 农药, 2010, 49,625.)
[28]	HRAC Classification on Mode of Action 2020. (accessed September 26, 2020). https://www.hracglobal.com.
[29]	Lu, X. L.; Zhu, X.; Zhang, M.; Wu, Q. L.; Zhou, X. D.; Li, J. K. Nat. Prod. Lett. 2019, 33,2145.
[30]	Cheng, C. R.; Zheng, Z.; Liang, R. M.; Li, F.; X. Jiang, Q. Q.; Yue, L.; Wang, Q.; Ding, J.; Liu, Y.. Chem. Nat. Compd. 2020, 56,264. doi: 10.1007/s10600-020-03003-4
[31]	Chen, Y.; Li, P.; Chen, M.; He, J.; Su, S. J.; He, M.; Wang, H.; Xue, W. J. Heterocycl. Chem. 2020, 57,1. doi: 10.1002/jhet.v57.1
[32]	Ruan, X. H.; Zhang, C.; Jiang, S. C.; Guo, T.; Xia, R. J.; Chen, Y.; Tang, X.; Xue, W. Molecules 2018, 23,3132. doi: 10.3390/molecules23123132
[33]	Barrows, R. D.; Hammill, J. T.; Michael, C. Tran, M. C.; Falade, M. O.; Rice, A. L.; Davis, C. W.; Emge, T. J.; Rablen, P. R.; Guy, R. K.; Knapp, S. Bioorg. Med. Chem. 2020 , 28, 115758..
[34]	Guo, Y.; Wang, X. G.; Fan, J. P.; Zhang, Q.; Wang, Y.; Zhao, Y.; Huang, M. X.; Ding, M.; Zhang, Y. B. Roy. Soc. Open Sci. 2017, 4,171053.
[35]	Yu, Y. P.; Duan, W. G.; Lin, G. S.; Kang, G. Q.; Wang, X. Y.; Lei, F. H. Chin. J. Org. Chem. 2020, 40,1647(in Chinese). doi: 10.6023/cjoc201912042
	( 虞友培, 段文贵, 林桂汕, 康国强, 王晓宇, 雷福厚, 有机化学, 2020, 40,1647.) doi: 10.6023/cjoc201912042
[36]	Li, F. Y.; Huang, L.; Zhou, X. Q.; Li, Q.; Ma, X. L.; Duan, W. G.; Wang, X. Chin. J. Org. Chem. 2020, 40,2845(in Chinese). doi: 10.6023/cjoc202003062
	( 李芳耀, 黄琳, 周小群, 李倩, 马献力, 段文贵, 王秀, 有机化学, 2020, 40,2845.) doi: 10.6023/cjoc202003062
[37]	Lin, G. S.; Chen, Z. C.; Duan, W. G.; Wang, X. Y.; Lei, F. H. Chin. J. Org. Chem. 2018, 38,2085(in Chinese). doi: 10.6023/cjoc201801043
	( 林桂汕, 陈智聪, 段文贵, 王晓宇, 雷福厚, 有机化学, 2018, 38,2085.) doi: 10.6023/cjoc201801043
[38]	He, Y.; Duan, W. G.; Lin, G. S.; Cen, B.; Bu, J. W.; Lei, F. H. Chem. Ind. Forest Prod. 2020, 40,76(in Chinese).
	( 何云, 段文贵, 林桂汕, 岑波, 卜俊文, 雷福厚, 林产化学与工业, 2020, 40,76.)
[39]	Lin, G. S.; Bai, X.; Duan, W. G.; Cen, B.; Huang, M.; Lu, S. Z. ACS Sustainable Chem. Eng. 2019, 7,7862. doi: 10.1021/acssuschemeng.9b00254
[40]	Lin, G. S.; Duan, W. G.; Yang, L. X.; Huang, M.; Lei, F. H. Molecules 2017, 22,193. doi: 10.3390/molecules22020193
[41]	Verma, J.; Khedkar, V. M.; Coutinho, E. C. Curr. Top. Med. Chem. 2010, 10,95. doi: 10.2174/156802610790232260
[42]	Li, L. H.; Li, Z. R.; Liu, M. L.; Shen, W. Y.; Wang, B.; Guo, H. Y.; Lu, Y. Molecules 2015, 21,49. doi: 10.3390/molecules21010049
[43]	Liu, M.X; Li, C. J.. Angew. Chem. Int. Ed. 2016, 55,10806. doi: 10.1002/anie.201604847
[44]	Li, L. H.; Li, Z. R.; Liu, M. L.; Shen, W. Y.; Wang, B.; Guo, H. Y.; Lu, Y. Molecules 2016, 21,49. doi: 10.3390/molecules21010049
[45]	Su, N. N.; Li, Y.; Yu, S. J.; Zhang, X.; Liu, X. H.; Zhao, W. G. Res. Chem. Intermediat. 2012, 39,759. doi: 10.1007/s11164-012-0595-9

Compd.	B. campestris		E. crusgalli
Compd.	10 μg/mL	100 μg/mL	10 μg/mL	100 μg/mL
Flumioxazin	57.8	63.0	95.1	97.5
5a	30.7	74.9	5.0	20.0
5b	68.9	86.9	15.0	40.0
5c	79.3	89.4	25.0	40.0
5d	41.7	90.5	0	0
5e	67.5	83.2	0	0
5f	38.3	76.8	0	0
5g	22.6	75.7	10.0	40.0
5h	25.3	77.4	35.0	70.0
5i	38.9	81.4	15.0	75.0
5j	10.0	47.9	20.0	50.0
5k	0	79.3	20.0	40.0
5l	34.0	73.0	35.0	55.0
5m	13.8	65.1	15.0	30.0
5n	4.6	31.8	10.0	25.0
5o	25.8	60.5	10.0	25.0
5p	4.6	18.7	0	0
5q	20.9	81.7	15.0	20.0
5r	29.6	52.3	20.0	50.0
5s	0	9.0	0	10.0
5t	23.7	57.8	0	0
5u	21.1	25.2	0	10.0
5v	37.2	79.1	0	0
5w	24.5	55.1	0	10.0
5x	60.7	83.2	0	10.0
5y	45.0	60.2	0	0
5z	30.8	85.6	0	0

Compd.	B. campestris		E. crusgalli
Compd.	10 μg/mL	100 μg/mL	10 μg/mL	100 μg/mL
Flumioxazin	57.8	63.0	95.1	97.5
5a	30.7	74.9	5.0	20.0
5b	68.9	86.9	15.0	40.0
5c	79.3	89.4	25.0	40.0
5d	41.7	90.5	0	0
5e	67.5	83.2	0	0
5f	38.3	76.8	0	0
5g	22.6	75.7	10.0	40.0
5h	25.3	77.4	35.0	70.0
5i	38.9	81.4	15.0	75.0
5j	10.0	47.9	20.0	50.0
5k	0	79.3	20.0	40.0
5l	34.0	73.0	35.0	55.0
5m	13.8	65.1	15.0	30.0
5n	4.6	31.8	10.0	25.0
5o	25.8	60.5	10.0	25.0
5p	4.6	18.7	0	0
5q	20.9	81.7	15.0	20.0
5r	29.6	52.3	20.0	50.0
5s	0	9.0	0	10.0
5t	23.7	57.8	0	0
5u	21.1	25.2	0	10.0
5v	37.2	79.1	0	0
5w	24.5	55.1	0	10.0
5x	60.7	83.2	0	10.0
5y	45.0	60.2	0	0
5z	30.8	85.6	0	0

q²	r²	S	N	F	Contribution/%
q²	r²	S	N	F	Steric	Electrostatic
0.603	0.996	0.040	6	337.11	36.2	63.8

q²	r²	S	N	F	Contribution/%
q²	r²	S	N	F	Steric	Electrostatic
0.603	0.996	0.040	6	337.11	36.2	63.8

Compd.	ED	ED''	Residue
5f	–1.97	–2.03	0.06
5g	–2.01	–2.00	–0.01
5h	–1.97	–1.97	0
5i	–1.89	–1.90	0.01
5j	–2.56	–2.56	0
5k	–1.93	–1.90	–0.03
5l	–2.08	–2.03	–0.05
5m	–2.24	–2.23	–0.01
5n	–2.86	–2.84	–0.02
5o	–2.35	–2.32	–0.03
5s	–3.55	–3.55	0
5t	–2.47	–2.45	–0.02
5u	–3.03	–3.05	0.02
5v	–1.96	–2.01	0.05
5w	–2.49	–2.52	0.03
5p*	–3.17	–3.06	–0.11
5q*	–1.94	–1.98	0.04
5r*	–2.55	–2.64	0.09