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

doi:10.6023/cjoc202208027

摘要/Abstract

为了寻找新颖和高效的杀线虫剂, 设计合成了28个2-氰基丙烯酸酯(酰胺)类衍生物, 并通过¹H NMR, ¹³C NMR和高分辨质谱(HRMS)对所有目标化合物结构进行了确证. (E)-3-(4-氯苯基)-2-氰基丙烯酸乙酯(3f)的构型通过X射线单晶衍射方法确认. 杀线虫活性测试结果显示, 在100 mg/L浓度下处理72 h后, 所有目标化合物对南方根结线虫、水稻干尖线虫和甘薯茎线虫(二龄幼虫)均具有一定的杀线虫活性. 其中, (E)-2-氰基-3-(4-氟苯基)丙烯酸乙酯(3i)和(E)-2-氰基-3-(呋喃-2-基)丙烯酸乙酯(3n)对南方根结线虫的LC₅₀分别为24.58和32.13 mg/L. (E)-3-[4-(2-((3-氯-5-(三氟甲基)吡啶-2-基)氧基)乙氧基)苯基]-2-氰基丙烯酸乙酯(17a)对水稻干尖线虫和甘薯茎线虫的LC₅₀分别为31.97和38.26 mg/L, 明显优于对照药剂Tioxazafen (48.95和74.95 mg/L). 此外, 化合物3i可以显著促进南方根结线虫体内活性氧(ROS)的产生、脂褐素和脂质的积累, 表明化合物3i可能通过促进线虫的氧化应激最终导致线虫死亡. 化合物3i可以作为先导化合物来开发新型杀线虫剂.

关键词: 2-氰基丙烯酸酯, 酰胺, 杀线虫活性, 南方根结线虫, 水稻干尖线虫, 甘薯茎线虫, 氧化应激

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

引用此文

王余, 陈艺方, 罗鑫, 邢志富, 彭菊, 陈吉祥. 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[J]. 有机化学, 2023, 43(6): 2206-2216.

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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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