3,7-二甲基辛-2,6-二烯酰胺和3,7-二甲基-6,7-二羟基辛-2-烯酰胺的合成及杀菌活性

doi:10.6023/cjoc202105009

摘要/Abstract

分别以(Z)-和(E)-香叶醇为原料, 设计合成了22个新的(Z)-和(E)-3,7-二甲基辛-2,6-二烯酰胺及光学活性(6R或6S)-3,7-二甲基-6,7-二羟基辛-2-烯酰胺, 它们的结构经过IR, ¹H NMR, ¹³C NMR和HR-ESI-MS表征. 离体杀菌活性测试结果显示, 部分化合物在50 µg/mL浓度时对水稻纹枯菌和油菜菌核菌等测试植物病原菌显示了一定的杀菌活性, 如(Z)-N-[2-(4-氯苯基)苯基]-3,7-二甲基辛-2,6-二烯酰胺(5d)、(6S,2Z)-N-[2-(4-氯苯基)苯基]-3,7-二甲基-6,7-二羟基辛-2-烯酰胺(7g)和(6R,2Z)-N-[2-(4-氯苯基)苯基]-3,7-二甲基-6,7-二羟基辛-2-烯酰胺(7h)对油菜菌核菌的EC₅₀分别为46.3, 38.1和40.6 µg/mL, (Z)-N-(4-叔丁基苄基)-3,7-二甲基辛-2,6-二烯酰胺(5b)对水稻纹枯菌的EC₅₀分别为20.5 µg/mL. 活体杀菌活性测试结果显示, 在400 µg/mL浓度下(Z)-N-(2-氯-4-三氟甲基苯基)-3,7-二甲基辛-2,6-二烯酰胺(5c)、(E)-N-(2-氯-4-三氟甲基苯基)-3,7-二甲基辛-2,6-二烯酰胺(5g)和(6S,2E)-N-(2-氯-4-三氟甲基苯基)-3,7-二甲基-6,7-二羟基辛-2-烯酰胺(7m)对黄瓜霜霉病和小麦白粉病的防效达到50%~100%, 具有进一步优化提高杀菌活性的潜力.

关键词: 3,7-二甲基辛-2,6-二烯酰胺, 3,7-二甲基-6,7-二羟基辛-2-烯酰胺, Sharpless不对称双羟基化反应, 杀菌活性

A series of novel (Z)- and (E)-3,7-dimethylocta-2,6-dienamides and optical (6R or 6S)-3,7-dimethyl-6,7-dihydroxyoct-2-enamides were designed and synthesized using (Z)- and (E)-geraniols as raw materials, respectively. Their structures were characterized by IR, ¹H NMR, ¹³C NMR and HR-ESI-MS spectra. The preliminary bioassay results indicated that some compounds exhibit certain in vitro fungicidal activities against Rhizoctonia solani and Sclerotinia sclerotiorum at the concentration of 50 µg/mL. For example, (Z)-N-(2-(4-chlorophenyl)phenyl)-3,7-dimethylocta-2,6-dienamide (5d), (6S,2Z)-N-(2- (4-chlorophenyl)phenyl)-3,7-dimethyl-6,7-dihydroxyoct-2-enamide (7g) and (6S,2Z)-N-(2-(4-chlorophenyl)phenyl)-3,7-dimethyl-6,7-dihydroxyoct-2-enamide (7h) have EC₅₀ values of 46.3, 38.1 and 40.6 µg/mL against S. sclerotiorum, and (Z)-N-(4-tert-butyl-benzyl)-3,7-dimethylocta-2,6-dienamide (5b) has an EC₅₀ value of 20.5 µg/mL against R. solani, respectively. The in vivo efficacy of (Z)-N-(2-chloro-4-trifluromethylphenyl)-3,7-dimethylocta-2,6-dienamide (5c), (E)-N-(2-chloro- 4-trifluromethylphenyl)-3,7-dimethylocta-2,6-dienamide (5g) and (6S,2E)-N-(2-chloro-4-trifluromethylphenyl)-3,7-dimethyl- 6,7-dihydroxyoct-2-enamide (7m) at the concentration of 400 µg/mL were in the range of 50%~100% against Pseudoperonospora cubensis and Erysiphe graminis. They have a potential to be optimized for improving the fungicidal activity.

Key words: 3,7-dimethylocta-2,6-dienamide, 3,7-dimethyl-6,7-dihydroxyoct-2-enamide, Sharpless asymmetric dihydroxylation, fungicidal activity

引用此文

王卫伟, 李益豪, 刘鑫磊, 赵宇, 王明安. 3,7-二甲基辛-2,6-二烯酰胺和3,7-二甲基-6,7-二羟基辛-2-烯酰胺的合成及杀菌活性[J]. 有机化学, 2021, 41(9): 3717-3725.

Weiwei Wang, Yihao Li, Xinlei Liu, Yu Zhao, Mingan Wang. Synthesis and Fungicidal Activity of Novel 3,7-Dimethylocta-2,6-dienamides and 3,7-Dimethyl-6,7-dihydroxyoct-2-enamides[J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3717-3725.

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

分享此文

图/表 6

参考文献 24

[1]	Zhang, Y.; Chen, Z.; Nie, J.; Zhang, F. G.; Ma, J. A. J. Org. Chem. 2019, 84, 7148. doi: 10.1021/acs.joc.9b00819 pmid: 31058497
[2]	Zhang, A.; Yue, Y.; Yang, J.; Shi, J.; Tao, K.; Jin, H.; Hou, T. J. Agric. Food Chem. 2019, 67, 5008.
[3]	Zhang, A.; Zhou, J.; Tao, K.; Hou, T.; Jin, H. Bioorg. Med. Chem. Lett. 2018, 28, 3042. doi: 10.1016/j.bmcl.2018.08.001
[4]	Walter, H.; Lamberth, C.; Corsi, C. Monatsh. Chem. 2018, 149, 791. doi: 10.1007/s00706-017-2101-y
[5]	Yan, Z.; Liu, A.; Huang, M.; Liu, M.; Pei, H.; Huang, L.; Yi, H.; Liu, W.; Hu, A. Eur. J. Med. Chem. 2018, 149, 170. doi: 10.1016/j.ejmech.2018.02.036
[6]	Mu, J. X.; Shi, Y. X.; Yang, M. Y.; Sun, Z. H.; Liu, X. H.; Li, B. J.; Sun N. B. Molecules 2016, 21, 68. doi: 10.3390/molecules21010068
[7]	Du, S.; Tian, Z.; Yang, D.; Li, X.; Li, H.; Jia, C.; Che, C.; Wang, M.; Qin Z. Molecules 2015, 20, 8395. doi: 10.3390/molecules20058395
[8]	Sun, J.; Zhou, Y. Molecules 2015, 20, 4383. doi: 10.3390/molecules20034383
[9]	Wu, J.; Wang, J.; Hu, D.; He, M.; Jin, L.; Song, B. Chem. Cent. J. 2012, 6, 51. doi: 10.1186/1752-153X-6-51
[10]	Gabriela, L.; Gallardo, N. I. P.; Cabrera, G. M. Phytochem. Lett. 2008, 1, 155. doi: 10.1016/j.phytol.2008.07.008
[11]	Yang, Y.; Jiang, J. Z.; Qimei, L. B.; Yan, X. J.; Zhao, J. X.; Yuan, H. Z.; Qin, Z. H.; Wang, M. A. Molecules 2010, 15, 7075. doi: 10.3390/molecules15107075 pmid: 20944522
[12]	Chen, J.; Zhu, C. L.; Xu, H. Y.; Ni, X.; Yang, P. M. Chin. J. Pharm. 2010, 41, 504. (in Chinese).
	( 陈佳, 朱超兰, 许海燕, 倪翔, 杨培明, 中国医药工业杂志, 2010, 41, 504.)
[13]	Lee, K. Y.; Kim, S. H.; Sung, S. H. Planta Med. 2008, 74, 867. doi: 10.1055/s-2008-1074552
[14]	Dong, H. B.; Yang, M. Y.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2013, 15, 880.
[15]	Dong, H. B.; Yang, M. Y.; Tang, B.; Wang, M. A. Chin. J. Org. Chem. 2014, 34, 2350. (in Chinese). doi: 10.6023/cjoc201406005
	( 董宏波, 杨明艳, 汤博, 王明安, 有机化学, 2014, 34, 2350.)
[16]	Dong, H. B.; Wang, W. W.; Zhao, Y.; Liu, X. L.; Wang, M. A. Chin. J. Org. Chem. 2021, 41, 1646. (in Chinese). doi: 10.6023/cjoc202010011
	( 董宏波, 王卫伟, 赵宇, 刘鑫磊, 王明安, 有机化学, 2021, 41, 1646.)
[17]	Wang, W. W.; Zhao, Y.; Liu, X. L.; Jiang, J. Z.; Wang, M. A. Chin. J. Org. Chem. 2021, 41, 2343. (in Chinese). doi: 10.6023/cjoc202101049
	( 王卫伟, 赵宇, 刘鑫磊, 蒋家珍, 王明安, 有机化学, 2021, 41, 2343.)
[18]	Zhao, J.; Dong, H. B.; Yang, M. Y.; Du, J.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2014, 16, 312.
[19]	Wang, W. W.; Zhang, X. T.; Zhao, Y.; Liu, X. L.; Zhang, Z. H.; Wang, M. A. Chin. Chem. Lett. 2018, 29, 1872. doi: 10.1016/j.cclet.2018.02.006
[20]	Yang, M. Y.; Dong, H. B.; Jiang, J. Z.; Wang, M. A. Molecules 2015, 20, 21023. doi: 10.3390/molecules201219743
[21]	Zhao, Y.; Tang, B.; Guan, A. Y.; Wang, W. W.; Zhang, Z. H.; Wang, M. A. Synthesis 2017, 49, 4663. doi: 10.1055/s-0036-1588463
[22]	Tang, B.; Guan, A. Y.; Zhao, Y.; Jiang, J. Z.; Wang, M. A.; Zhou, L. G. Chin. J. Chem. 2017, 35, 1133. doi: 10.1002/cjoc.v35.7
[23]	Guan, A. Y.; Liu, C. L.; Chen, W.; Yang, F.; Xie, Y.; Zhang, J. B.; Li, Z. N.; Wang, M. A. J. Agric. Food Chem. 2017, 65, 1272.
[24]	Guan, A. Y.; Wang, M. A.; Yang, J. L.; Wang, L. Z.; Xie, Y.; Lan, J.; Liu, C. L. J. Agric. Food Chem. 2017, 65, 10829.

化合物	构型	R¹R²	水稻纹枯菌	辣椒疫霉菌	油菜菌核菌	黄瓜灰霉菌	棉花立枯菌
5a	2Z	Morpholino	18.3	12.5	6.3	11.3	7.5
5b	2Z	4-t-BuC₆H₄CH₂, H	60.6	10.0	30.6	30.6	10.0
5c	2Z	2-Cl-4-CF₃C₆H₄, H	51.1	2.5	0	15.6	14.4
5d	2Z	2-(4-Cl-C₆H₄)C₆H₄, H	37.8	6.3	65.6	23.1	8.1
5e	2E	Morpholino	43.3	17.5	0	33.8	8.8
5f	2E	4-t-ButC₆H₄CH₂, H	41.1	9.4	48.8	36.3	11.3
5g	2E	2-Cl-4-CF₃C₆H₄, H	31.1	0	15.6	10.0	11.3
5h	2E	2-(4-Cl-C₆H₄)C₆H₄, H	35.6	3.8	0	10.0	11.9
7a	2Z,6S	Morpholino	41.1	10.0	8.1	6.3	12.5
7b	2Z,6R	Morpholino	43.3	11.3	49.4	12.5	12.5
7c	2Z,6S	4-t-ButC₆H₄CH₂, H	28.9	14.4	27.5	43.1	9.4
7d	2Z,6R	4-t-ButC₆H₄CH₂, H	23.3	13.8	21.3	34.4	16.3
7e	2Z,6S	2-Cl-4-CF₃C₆H₄, H	41.1	21.3	54.4	35.6	18.8
7f	2Z,6R	2-Cl-4-CF₃C₆H₄, H	29.4	15.0	27.5	11.9	17.5
7g	2Z,6S	2-(4-Cl-C₆H₄)C₆H₄, H	30.0	28.1	71.3	51.3	8.1
7h	2Z,6R	2-(4-Cl-C₆H₄)C₆H₄, H	53.9	25.6	61.3	40.6	9.4
7i	2E,6S	Morpholino	23.9	8.1	29.4	36.9	5.0
7j	2E,6R	Morpholino	34.4	8.8	58.8	30.6	0
7k	2E,6S	4-t-ButC₆H₄CH₂, H	25.6	12.5	12.5	30.0	10.0
7l	2E,6R	4-t-ButC₆H₄CH₂, H	39.4	18.8	29.4	27.5	10.0
7m	2E,6S	2-Cl-4-CF₃C₆H₄, H	41.7	27.5	51.3	22.5	23.8
7n	2E,6R	2-Cl-4-CF₃C₆H₄, H	38.9	26.9	54.4	26.3	17.5
7o	2E,6S	2-(4-Cl-C₆H₄)C₆H₄, H	21.7	10.0	12.5	12.5	0
7p	2E,6R	2-(4-Cl-C₆H₄)C₆H₄, H	32.2	13.1	34.4	25.6	16.9
R-1			71.8	66.4	81.8	72.0	80.2
丁吡吗啉			61.6	100	74.4	68.1	37.2
烯酰吗啉			14.6	100	15.0	9.4	20.9

化合物	构型	R¹R²	水稻纹枯菌	辣椒疫霉菌	油菜菌核菌	黄瓜灰霉菌	棉花立枯菌
5a	2Z	Morpholino	18.3	12.5	6.3	11.3	7.5
5b	2Z	4-t-BuC₆H₄CH₂, H	60.6	10.0	30.6	30.6	10.0
5c	2Z	2-Cl-4-CF₃C₆H₄, H	51.1	2.5	0	15.6	14.4
5d	2Z	2-(4-Cl-C₆H₄)C₆H₄, H	37.8	6.3	65.6	23.1	8.1
5e	2E	Morpholino	43.3	17.5	0	33.8	8.8
5f	2E	4-t-ButC₆H₄CH₂, H	41.1	9.4	48.8	36.3	11.3
5g	2E	2-Cl-4-CF₃C₆H₄, H	31.1	0	15.6	10.0	11.3
5h	2E	2-(4-Cl-C₆H₄)C₆H₄, H	35.6	3.8	0	10.0	11.9
7a	2Z,6S	Morpholino	41.1	10.0	8.1	6.3	12.5
7b	2Z,6R	Morpholino	43.3	11.3	49.4	12.5	12.5
7c	2Z,6S	4-t-ButC₆H₄CH₂, H	28.9	14.4	27.5	43.1	9.4
7d	2Z,6R	4-t-ButC₆H₄CH₂, H	23.3	13.8	21.3	34.4	16.3
7e	2Z,6S	2-Cl-4-CF₃C₆H₄, H	41.1	21.3	54.4	35.6	18.8
7f	2Z,6R	2-Cl-4-CF₃C₆H₄, H	29.4	15.0	27.5	11.9	17.5
7g	2Z,6S	2-(4-Cl-C₆H₄)C₆H₄, H	30.0	28.1	71.3	51.3	8.1
7h	2Z,6R	2-(4-Cl-C₆H₄)C₆H₄, H	53.9	25.6	61.3	40.6	9.4
7i	2E,6S	Morpholino	23.9	8.1	29.4	36.9	5.0
7j	2E,6R	Morpholino	34.4	8.8	58.8	30.6	0
7k	2E,6S	4-t-ButC₆H₄CH₂, H	25.6	12.5	12.5	30.0	10.0
7l	2E,6R	4-t-ButC₆H₄CH₂, H	39.4	18.8	29.4	27.5	10.0
7m	2E,6S	2-Cl-4-CF₃C₆H₄, H	41.7	27.5	51.3	22.5	23.8
7n	2E,6R	2-Cl-4-CF₃C₆H₄, H	38.9	26.9	54.4	26.3	17.5
7o	2E,6S	2-(4-Cl-C₆H₄)C₆H₄, H	21.7	10.0	12.5	12.5	0
7p	2E,6R	2-(4-Cl-C₆H₄)C₆H₄, H	32.2	13.1	34.4	25.6	16.9
R-1			71.8	66.4	81.8	72.0	80.2
丁吡吗啉			61.6	100	74.4	68.1	37.2
烯酰吗啉			14.6	100	15.0	9.4	20.9

化合物	黄瓜霜霉病	小麦白粉病	化合物	黄瓜霜霉病	小麦白粉病	玉米锈病	苹果炭疽病
5a	0	0	7f	0	0	0	0
5b	0	0	7g	0	0	0	0
5c	85	80	7h	0	0	0	0
5d	0	0	7i	0	0	0	0
5e	0	0	7j	0	0	0	0
5f	0	0	7k	0	0	0	0
5g	85	100	7l	0	0	0	0
5h	0	0	7m	50	70	0	0
7a	0	0	7n	0	0	0	0
7b	0	0	7o	0	0	0	0
7c	0	0	7p	0	0	0	0
7d	0	0	(Z,R)-2^[19]	100	100	60	65
7e	0	0	(Z,S)-2^[19]	100	100	80	100

化合物	黄瓜霜霉病	小麦白粉病	化合物	黄瓜霜霉病	小麦白粉病	玉米锈病	苹果炭疽病
5a	0	0	7f	0	0	0	0
5b	0	0	7g	0	0	0	0
5c	85	80	7h	0	0	0	0
5d	0	0	7i	0	0	0	0
5e	0	0	7j	0	0	0	0
5f	0	0	7k	0	0	0	0
5g	85	100	7l	0	0	0	0
5h	0	0	7m	50	70	0	0
7a	0	0	7n	0	0	0	0
7b	0	0	7o	0	0	0	0
7c	0	0	7p	0	0	0	0
7d	0	0	(Z,R)-2^[19]	100	100	60	65
7e	0	0	(Z,S)-2^[19]	100	100	80	100