Design, Synthesis and Nematicidal Activity of Novel 2-Cyanoacrylate (Amide) Derivatives

doi:10.6023/cjoc202208027

Abstract

To find novel and efficient nematicides, 28 2-cyanoacrylate (amide) derivatives were designed and synthesized. The structures of all target compounds were confirmed by ¹H NMR, ¹³C NMR, and high-resolution mass spectra (HRMS). The configuration of ethyl (E)-3-(4-chlorophenyl)-2-cyanoacrylate (3f) was confirmed by X-ray single crystal diffraction. The results of nematicidal activities test showed that all the target compounds had certain nematicidal activities against Meloidogyne incognita, Aphelenchoides besseyi, and Ditylenchus destructor (second-stage juveniles) after 72 h of treatment at 100 mg/L. Among them, the LC₅₀s of ethyl (E)-2-cyano-3-(4-fluorophenyl)acrylate (3i) and ethyl (E)-2-cyano-3-(furan-2-yl)- acrylate (3n) against Meloidogyne incognita for 72 h were 24.58 and 32.13 mg/L, respectively. The LC₅₀s of ethyl (E)-3-(4-(2- ((3-chloro-5-(trifluoromethyl)pyridin-2-yl)oxy)ethoxy)phenyl)-2-cyanoacrylate (17a) against A. besseyi and D. destructor were 31.97 and 38.26 mg/L, respectively, which were significantly better than that of the control agent Tioxazafen (48.95 and 74.95 mg/L). In addition, compound 3i could significantly promote the production of reactive oxygen species (ROS) and the accumulation of lipofuscin and lipid in M. incognita, which indicated that compound 3i might promote oxidative stress of M. incognita and eventually lead to the death of nematodes. Compound 3i can be used as a lead compound to develop novel nematicides.

Key words: 2-cyanoacrylate, amide, nematicidal activity, Meloidogyne incognita, Aphelenchoides besseyi, Ditylenchus destructor, oxidative stress

Cite this article

Yu Wang, Yifang Chen, Xin Luo, Zhifu Xing, Ju Peng, Jixiang Chen. Design, Synthesis and Nematicidal Activity of Novel 2-Cyanoacrylate (Amide) Derivatives[J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 2206-2216.

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References 31

[1]	Blaxter, M. PLoS Biol. 2011, 9, e1001050. doi: 10.1371/journal.pbio.1001050
[2]	Wang, G. L.; Chen, X. L.; Deng, Y. Y.; Li, Z.; Xu, X. Y. J. Agric. Food Chem. 2015, 63, 6883.
[3]	Abad, P.; Favery, B.; Rosso, M. N.; Castagnone, S. P. Mol. Plant Pathol. 2003, 4, 217. doi: 10.1046/j.1364-3703.2003.00170.x
[4]	Wang, F.; Zhang, L. H.; Wang, Z. M. China Plant Prot. 2017, 37, 54.
[5]	Zhuang, H. C.; Ying, Y. X. Plant Prot. 2016, 490, 77. (in Chinese)
	(庄会存, 尹永霞, 植物保护, 2016, 490, 77.)
[6]	Kumar, R. M.; Rao, M.; Reddy, M.; Wang, Q; Li, Y.; Zhang, L.; Du, B.; Yellareddygari, S. Egypt. J. Biol. Pest Control. 2011, 456.
[7]	Collange, B.; Navarrete, M.; Peyre, G.; Mateille, T.; Tchamitchian, M. Crop Prot. 2011, 30, 1251. doi: 10.1016/j.cropro.2011.04.016
[8]	Keiser, J.; Utzinger, J. Jama 2008, 299, 1937.
[9]	Meher, H. C.; Gajbhiye, V. T.; Chawla, G.; Singh, G. Pest Manage. Sci. 2009, 65, 1201. doi: 10.1002/ps.1810
[10]	Fuller, V. L.; Lilley, C. J.; Urwin, P. E. New Phytol. 2008, 180, 27. doi: 10.1111/nph.2008.180.issue-1
[11]	Chen, J. X.; Song, B. A. J. Integr. Agric. 2021, 20, 2015. doi: 10.1016/S2095-3119(21)63617-1
[12]	Nguyen, L. T.; Jang, J. Y.; Kim, T. Y.; Yu, N. H.; Park, A. R.; Lee, S.; Bae, C. H.; Yeo, J. H.; Hur, J. S.; Park, H. W.; Kim, J. C. Pestic. Biochem. Physiol. 2018, 148, 133. doi: S0048-3575(17)30508-4 pmid: 29891364
[13]	Dang, Q. L.; Kim, W. K.; Nguyen, C. M.; Choi, Y. H.; Choi, G. J.; Jang, K. S.; Park, M. S.; Lim, C. H.; Luu, N. H.; Kim, J. C. J. Agric. Food Chem. 2011, 59, 11160. doi: 10.1021/jf203017f
[14]	Caboni, P.; Saba, M.; Oplos, C.; Aissani, N.; Maxia, A.; Menkissoglu-Spiroudi, U.; Casu, L.; Ntalli, N. Pest Manage. Sci. 2015, 71, 1099. doi: 10.1002/ps.2015.71.issue-8
[15]	Jia, H. W.; Guo, W.; Li, W.; Li, T. F.; Chen, X. L.; Li, Z.; Xu, X. Y. J. Chem. Res. 2019, 43, 161. doi: 10.1177/1747519819857506
[16]	Chen, J.X.; Qing, X. L.; Song, B. A. J. Agric. Food Chem. 2020, 68, 12175. doi: 10.1021/acs.jafc.0c02871
[17]	Jeschke, P. Pest Manage. Sci. 2017, 73, 1053. doi: 10.1002/ps.2017.73.issue-6
[18]	Jeschke, P. Pest Manage. Sci. 2016, 72, 433. doi: 10.1002/ps.2016.72.issue-3
[19]	Lahm, G. P.; Desaeger, J.; Smith, B. K.; Thomas, F. P.; Michel, A. R.; Tony, M.; Roman, K.; Renee, M. L.; Anne, D.; Brenton, T. S.; Daniel, C.; Tim, T.; John, A. W. Bioorg. Med. Chem. Lett. 2017, 27, 1572. doi: 10.1016/j.bmcl.2017.02.029
[20]	Chen, J. X.; Yi, C.F.; Wang, S. B.; Wu, S.K.; Li, S. Y.; Hu, D. Y.; Song, B. A. Bioorg. Med. Chem. Lett. 2019, 29, 1203. doi: 10.1016/j.bmcl.2019.03.017
[21]	Rajasekharan, S. K.; Lee, J.-H.; Ravichandran, V.; Kim, J.-C.; Park, J. G.; Lee, J. Sci. Rep. 2019, 9, 2010. doi: 10.1038/s41598-019-38561-3 pmid: 30765810
[22]	Satish, K. R.; Seulbi, K.; Kim, J. C.; Jintae, L. Pestic. Biochem. Phys. 2020, 163, 76. doi: 10.1016/j.pestbp.2019.10.012
[23]	Rajasekharan, S. K.; Lee, J.-H.; Ravichandran, V.; Lee, J. Sci. Rep. 2017, 7, 6803. doi: 10.1038/s41598-017-07074-2 pmid: 28754990
[24]	Yu, Y.; Hua, X.; Chen, H.; Wang, Y.; Li, Z.; Han, Y.; Xiang, M. Environ. Pollut. 2020, 264, 114731. doi: 10.1016/j.envpol.2020.114731
[25]	Wei, C. Q.; Huang, J. J.; Luo, Y. Q.; Wang, S. B.; Wu, S. K.; Xing, Z. F.; Chen, J. X. Pestic. Biochem. Physiol. 2021, 175, 104857. doi: 10.1016/j.pestbp.2021.104857
[26]	Yang, H. Y.; Zhang, W.; Liu, Q. ChemistrySelect 2019, 4, 10819. doi: 10.1002/slct.v4.36
[27]	Krishnan, G. R.; Sreekumar, K. Eur. J. Org. Chem. 2008, 4763.
[28]	Jia, X. L.; Zhang, X. Y.; Wang, Z. J.; Zhao, S. H. Synth. Commun. 2022, 52, 774. doi: 10.1080/00397911.2022.2053992
[29]	Oskooie, H. A.; Roomizadeh, E.; Heravi, M. M. J. Chem. Res. 2006, 246.
[30]	Shen, Y.; Yang, B. Synth. Commun. 1989, 3069.
[31]	Paliwal, P.; Jetti, S. R.; Jain, S. Chem. Sci. Trans. 2012, 1, 494. doi: 10.7598/cst2012

化合物	南方根结线虫		水稻干尖线虫		甘薯茎线虫
化合物	50 mg/L	100 mg/L	50 mg/L	100 mg/L	50 mg/L	100 mg/L
3a	56.0±5.5	71.2±3.0	6.3±2.5	11.4±2.2	14.4±2.3	17.3±3.5
3b	56.6±4.7	62.8±6.7	0	7.8±2.1	7.8±0.7	13.5±2.1
3c	45.8±4.5	54.9±1.4	0	9.6±2.4	0	8.4±2.0
3d	47.0±3.4	67.0±6.8	0	8.3±2.7	11.5±3.0	14.5±0.9
3e	48.5±3.6	74.6±1.2	5.2±1.4	20.3±1.9	18.3±4.6	31.0±0.8
3f	32.8±2.1	95.5±4.0	10.2±2.3	59.7±5.9	0	11.5±1.1
3g	42.2±7.3	92.5±2.2	29.7±1.5	53.9±7.0	6.5±1.2	17.3±3.0
3h	61.2±2.3	75.8±7.5	26.2±2.8	33.4±5.2	0	8.7±3.2
3i	98.2±0.7	100	6.3±0.6	20.3±4.0	9.4±2.4	11.9±4.1
3j	54.9±2.3	65.7±5.0	14.7±2.7	50.9±4.4	8.5±2.1	12.7±3.4
3k	30.9±3.2	57.0±2.3	16.8±5.5	38.8±3.1	5.9±2.9	24.1±2.8
3l	50.2±4.8	93.0±1.4	30.7±2.7	77.2±4.9	9.0±2.2	23.1±4.6
3m	14.2±3.6	26.4±3.1	46.4±7.4	96.7±1.0	0	9.9±1.6
3n	82.2±3.7	96.3±0.5	20.2±2.4	32.2±4.6	0	13.7±1.4
6a	40.0±4.7	83.7±3.5	0	8.1±3.2	12.8±2.3	22.1±1.4
6b	33.2±1.3	54.9±4.1	15.5±4.2	29.3±4.3	11.1±2.4	16.9±1.4
7a	22.8±4.8	39.3±2.7	0	11.5±2.5	15.1±9.6	21.1±1.7
7b	9.9±3.2	33.3±9.1	13.0±2.9	19.4±3.2	15.5±3.4	19.3±3.9
7c	12.1±2.1	21.2±2.2	0	13.1±2.3	10.8±4.4	16.0±1.2
11a	11.0±4.6	22.5±3.9	0	8.6±2.2	7.8±1.0	14.3±1.4
11b	10.7±6.2	17.5±1.4	8.2±2.2	13.7±1.6	8.5±2.8	21.4±2.5
11c	4.8±1.3	11.6±1.5	0	10.2±2.9	7.4±2.6	13.5±1.6
11d	13.2±3.9	22.4±1.7	6.1±2.1	14.8±1.6	0	12.4±1.4
11e	27.5±7.3	37.1±8.9	6.8±2.6	15.2±1.8	6.3±1.0	16.7±0.6
11f	17.8±0.7	30.8±6.6	0	10.4±2.3	0	10.5±1.7
11g	29.7±3.8	39.5±5.8	5.6±2.0	14.6±2.7	12.7±2.0	20.7±2.6
17a	6.9±0.3	38.5±4.0	89.3±4.6	100	83.6±5.8	100
17b	12.6±1.4	34.4±3.3	20.3±3.7	29.9±2.4	10.5±1.5	14.9±2.6
氟吡菌酰胺	100	100	100	100	100	100
Tioxazafen			62.9±7.4	93.4±2.1	46.7±7.4	90.0±2.1

化合物	南方根结线虫		水稻干尖线虫		甘薯茎线虫
化合物	50 mg/L	100 mg/L	50 mg/L	100 mg/L	50 mg/L	100 mg/L
3a	56.0±5.5	71.2±3.0	6.3±2.5	11.4±2.2	14.4±2.3	17.3±3.5
3b	56.6±4.7	62.8±6.7	0	7.8±2.1	7.8±0.7	13.5±2.1
3c	45.8±4.5	54.9±1.4	0	9.6±2.4	0	8.4±2.0
3d	47.0±3.4	67.0±6.8	0	8.3±2.7	11.5±3.0	14.5±0.9
3e	48.5±3.6	74.6±1.2	5.2±1.4	20.3±1.9	18.3±4.6	31.0±0.8
3f	32.8±2.1	95.5±4.0	10.2±2.3	59.7±5.9	0	11.5±1.1
3g	42.2±7.3	92.5±2.2	29.7±1.5	53.9±7.0	6.5±1.2	17.3±3.0
3h	61.2±2.3	75.8±7.5	26.2±2.8	33.4±5.2	0	8.7±3.2
3i	98.2±0.7	100	6.3±0.6	20.3±4.0	9.4±2.4	11.9±4.1
3j	54.9±2.3	65.7±5.0	14.7±2.7	50.9±4.4	8.5±2.1	12.7±3.4
3k	30.9±3.2	57.0±2.3	16.8±5.5	38.8±3.1	5.9±2.9	24.1±2.8
3l	50.2±4.8	93.0±1.4	30.7±2.7	77.2±4.9	9.0±2.2	23.1±4.6
3m	14.2±3.6	26.4±3.1	46.4±7.4	96.7±1.0	0	9.9±1.6
3n	82.2±3.7	96.3±0.5	20.2±2.4	32.2±4.6	0	13.7±1.4
6a	40.0±4.7	83.7±3.5	0	8.1±3.2	12.8±2.3	22.1±1.4
6b	33.2±1.3	54.9±4.1	15.5±4.2	29.3±4.3	11.1±2.4	16.9±1.4
7a	22.8±4.8	39.3±2.7	0	11.5±2.5	15.1±9.6	21.1±1.7
7b	9.9±3.2	33.3±9.1	13.0±2.9	19.4±3.2	15.5±3.4	19.3±3.9
7c	12.1±2.1	21.2±2.2	0	13.1±2.3	10.8±4.4	16.0±1.2
11a	11.0±4.6	22.5±3.9	0	8.6±2.2	7.8±1.0	14.3±1.4
11b	10.7±6.2	17.5±1.4	8.2±2.2	13.7±1.6	8.5±2.8	21.4±2.5
11c	4.8±1.3	11.6±1.5	0	10.2±2.9	7.4±2.6	13.5±1.6
11d	13.2±3.9	22.4±1.7	6.1±2.1	14.8±1.6	0	12.4±1.4
11e	27.5±7.3	37.1±8.9	6.8±2.6	15.2±1.8	6.3±1.0	16.7±0.6
11f	17.8±0.7	30.8±6.6	0	10.4±2.3	0	10.5±1.7
11g	29.7±3.8	39.5±5.8	5.6±2.0	14.6±2.7	12.7±2.0	20.7±2.6
17a	6.9±0.3	38.5±4.0	89.3±4.6	100	83.6±5.8	100
17b	12.6±1.4	34.4±3.3	20.3±3.7	29.9±2.4	10.5±1.5	14.9±2.6
氟吡菌酰胺	100	100	100	100	100	100
Tioxazafen			62.9±7.4	93.4±2.1	46.7±7.4	90.0±2.1

化合物	y=ax+b	LC₅₀/(mg•L^–1)	R²	化合物	y=ax+b	LC₅₀/(mg•L^–1)	R²
3i	y=1.92x+2.33	24.58±1.22	0.96	氟吡菌酰胺	y=1.92x+4.04	3.16±0.62	0.95
3n	y=3.59x–0.41	32.13±1.57	0.97

化合物	y=ax+b	LC₅₀/(mg•L^–1)	R²	化合物	y=ax+b	LC₅₀/(mg•L^–1)	R²
3i	y=1.92x+2.33	24.58±1.22	0.96	氟吡菌酰胺	y=1.92x+4.04	3.16±0.62	0.95
3n	y=3.59x–0.41	32.13±1.57	0.97

化合物	水稻干尖线虫			甘薯茎线虫
化合物	y=ax+b	LC₅₀/(mg•L^–1)	R²	y=ax+b	LC₅₀/(mg•L^–1)	R²
17a	y=3.13x+0.29	31.97±3.27	0.91	y=2.49x+1.05	38.58±2.39	0.99
氟吡菌酰胺	y=3.13x+6.98	0.23±0.03	0.93	y=1.58x+6.01	0.23±0.05	0.94
Tioxazafen	y=1.97x+1.91	37.03±2.60	0.95	y=2.17x+1.03	67.53±9.43	0.99

新型2-氰基丙烯酸酯(酰胺)类衍生物的设计合成及杀线虫活性研究