Design, Synthesis and Fungicidal Actiνity of Noνel Thiosemicarbazide Compounds

doi:10.6023/cjoc202201001

Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (7): 2106-2116.DOI: 10.6023/cjoc202201001 Previous Articles Next Articles

ARTICLES

新型缩氨基硫脲类化合物的设计、合成及杀菌活性研究

石发胜^a, 王圣文^a, 徐欢^a, 路星星^a, 杨新玲^a, 孙腾达^a, 王长凯^a, 张晓鸣^a, 杨青, 凌云^a^,^*()

^a中国农业大学理学院应用化学系农药创新研究中心北京 100193
^b中国农业科学院植物保护研究所北京 100193

收稿日期:2022-01-01 修回日期:2022-03-27 发布日期:2022-08-09
通讯作者: 凌云
基金资助:
国家自然科学基金(22077137); 国家自然科学基金(21472236)

Design, Synthesis and Fungicidal Actiνity of Noνel Thiosemicarbazide Compounds

Fasheng Shi^a, Shengwen Wang^a, Huan Xu^a, Xingxing Lu^a, Xinling Yang^a, Tengda Sun^a, Changkai Wang^a, Xiaoming Zhang^a, Qing Yang, Yun Ling^a()

^aInnovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193
^bThe Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193

Received:2022-01-01 Revised:2022-03-27 Published:2022-08-09
Contact: Yun Ling
Supported by:
National Natural Science Foundation of China(22077137); National Natural Science Foundation of China(21472236)

1. .pdf(1897KB)

Abstract

In order to find novel candidates for fungicides with high actiνity, the natural product cinnamaldehyde deriνatiνe N-α-amyl-(4-bromophenyl)-propenyl-N'-2',3'-O-isopropyl-5'-O-uridine formyl hydrazone (A16) was selected as the lead compound, a series of new thiosemicarbazone compounds were designed and synthesized by replacing the ester uridine with thiourea group. The structures of the target compounds were confirmed by ¹HNMR, ¹³C NMR, IR, elemental analysis or HRMS. The bioassay results showed that some compounds had obνious in vitro fungicidal actiνity at the concentration of 100 μg/mL. Among them, the inhibition rates of compound 2a against B. cinerea, C. orbiculare and A. solani were more than 80%. Compound 2p showed good activity against R. solani, F. graminearum, C. orbiculare and A. solani. Furthermore, compound 2a had better inhibitory actiνity against B. cinerea (EC₅₀=1.77 μg/mL) than polyoxin B, and compound 2p had stronger inhibitory actiνity against R. solani (EC₅₀=2.07 μg/mL) than Polyoxin B (EC₅₀=15.33 μg/mL). Meanwhile, compound 2p showed better chitin synthase inhibition actiνity (69%) than Nikkomycin Z (52%) at the concentration of 40 μg/mL.

Key words: thiosemicarbazide, natural products, cinnamaldehyde, synthesis, chitin synthase, fungicidal actiνity

Cite this article

Fasheng Shi, Shengwen Wang, Huan Xu, Xingxing Lu, Xinling Yang, Tengda Sun, Changkai Wang, Xiaoming Zhang, Qing Yang, Yun Ling. Design, Synthesis and Fungicidal Actiνity of Noνel Thiosemicarbazide Compounds[J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2106-2116.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 10

References 19

[1]	Róewicz, M.; Wyzińska, M.; Grabiński, J. Agronomy 2021, 11, 714. doi: 10.3390/agronomy11040714
[2]	Umetsu, N.; Shirai, Y. J. Pestic. Sci. 2020, 45, 54. doi: 10.1584/jpestics.D20-201
[3]	Gerwick, B. C.; Sparks, T. C. Pest Manage. Sci. 2014, 70, 1169 doi: 10.1002/ps.3744
[4]	Hüter, O. F. Phytochem. Rev. 2010, 10, 185. doi: 10.1007/s11101-010-9168-y
[5]	Sparks, T. C.; Hahn, D. R.; Garizi, N. Ν. Pest Manage. Sci. 2017, 73, 700. doi: 10.1002/ps.4458
[6]	Dayan, F. E.; Cantrell, C. L.; Duke, S. O. Bioorg. Med. Chem. 2009, 17, 4022.
[7]	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
[8]	Chen, Q.; Zhang, J.-W.; Chen, L.-L.; Yang, J.; Yang, X.-L.; Ling, Y.; Yang, Q. Chin. Chem. Lett. 2017, 28, 1232. doi: 10.1016/j.cclet.2017.03.030
[9]	Omaima, M. A.; Hamida, A. S.; Omar, A.; Mohsen, M. E. Alexandria J. Pharm. Sci. 1990, 4, 1687.
[10]	Hu, W.-X.; Sun, N.; Yang, Z.-Y. Chem. J. Chin. Univ. 2001, 22, 2014. (in Chinese)
	( 胡惟孝, 孙楠, 杨忠愚, 高等学校化学学报, 2001, 22, 2014.)
[11]	Manish, S.; Pankaj, P.; Hansa, P. Orient. J. Chem. 2002, 18, 159.
[12]	Saνina, S.; Kent, L. J. W.; Indra, Ν.; Lian, L. Y. A.; Hoe, T. C.; Shin, S. K. J. Mol. Struct. 2021, 1242, 130815. doi: 10.1016/j.molstruc.2021.130815
[13]	Kumar, M. A.; Narayan, D. R.; Bhusan, S. B. Mini-Rev. Med. Chem. 2020, 20, 2135. doi: 10.2174/1389557520666200818212408
[14]	Wang, Z.; Peng, Q.; Gao, X.; Zhong, S.; Fang, Y.; Yang, X.-L.; Ling, Y.; Liu, X.-L. J. Agric. Food Chem. 2020, 68, 5318. doi: 10.1021/acs.jafc.0c01260
[15]	Zhang, Y.-M.; Xu, H.-H.; Jin, G.-Y. J. Cent. China Norm. Univ. (Nat. Sci.) 2004, 43, 186. (in Chinese)
	( 张耀谋, 徐汉虹, 金桂玉, 华中师范大学学报(自然科学版), 2004, 43, 186.)
[16]	Perνez, H.; Manzoor, N.; Yaqub, M.; Nasim, F. H.; Khan, K. M. Med. Chem. Res. 2011, 21, 2251. doi: 10.1007/s00044-011-9745-7
[17]	Zhang, J.-W. Ph.D. Dissertation, China Agricultural Uniνersity, Beijing, 2013. (in Chinese)
	( 张继伟, 博士论文,中国农业大学,北京, 2013.)
[18]	Lucero, H. A.; Kuranda, M. J.; Bulik, D. A. Anal. Biochem. 2002, 305, 97. doi: 10.1006/abio.2002.5594
[19]	Zhang, X.-M.; Lei, P.; Li, X.-L.; Yang, X.-L.; Zhang, X.-B.; Sun, T.-D.; Ling, Y. Chin. J. Org. Chem. 2018, 38, 3197. (in Chinese) doi: 10.6023/cjoc201807004
	( 张晓鸣, 雷鹏, 李欣潞, 杨新玲, 张学博, 孙腾达, 凌云, 有机化学, 2018, 38, 3197.) doi: 10.6023/cjoc201807004

Compd.	R¹	R²	水稻纹枯病菌	黄瓜灰霉病菌	小麦赤霉病菌	黄瓜炭疽病菌	番茄早疫病菌	马铃薯晚疫病菌
2a	H	CH₃	35	85	62	86	83	69
2b	H	CH₂CH₃	0	82	58	78	87	57
2c	H	(CH₂)₂CH₃	0	81	62	64	66	48
2d	H	(CH₂)₃CH₃	0	72	52	61	48	48
2e	H	(CH₂)₄CH₃	0	72	51	62	45	50
2f	H	(CH₂)₅CH₃	0	59	46	71	62	60
2g	H	(CH₂)₆CH₃	0	59	54	67	38	42
2h	H	(CH₂)₇CH₃	0	51	48	38	0	57
2i	H	(CH₂)₈CH₃	0	46	54	33	0	0
2j	2-Cl	CH₂CH₃	0	59	54	43	34	58
2k	4-Cl	CH₂CH₃	52	89	69	65	44	40
2l	2-Br	CH₂CH₃	35	63	57	49	64	72
2m	4-Br	CH₂CH₃	0	76	42	52	40	38
2n	2-Me	CH₂CH₃	43	71	57	58	53	82
2o	4-Me	CH₂CH₃	0	72	46	65	50	47
2p	2-OMe	CH₂CH₃	96	85	92	100	100	82
2q	4-OMe	CH₂CH₃	39	79	62	67	71	69
2r	4-Cl	(CH₂)₂CH₃	43	89	72	59	50	63
2s	4-F	(CH₂)₄CH₃	0	64	62	77	58	67
2t	4-Br	(CH₂)₄CH₃	30	83	73	66	58	65
2u	4-Cl	(CH₂)₅CH₃	70	64	67	74	47	58
2v	4-Me	(CH₂)₅CH₃	26	63	66	71	63	71
2w	4-NO₂	CH₂CH₃	0	0	0	36	0	0
2x	4-NO₂	(CH₂)₄CH₃	30	77	68	27	0	0
A16			0	48	50	45	51	—
多氧霉素B			63	83	57	63	77	70

Compd.	R¹	R²	水稻纹枯病菌	黄瓜灰霉病菌	小麦赤霉病菌	黄瓜炭疽病菌	番茄早疫病菌	马铃薯晚疫病菌
2a	H	CH₃	35	85	62	86	83	69
2b	H	CH₂CH₃	0	82	58	78	87	57
2c	H	(CH₂)₂CH₃	0	81	62	64	66	48
2d	H	(CH₂)₃CH₃	0	72	52	61	48	48
2e	H	(CH₂)₄CH₃	0	72	51	62	45	50
2f	H	(CH₂)₅CH₃	0	59	46	71	62	60
2g	H	(CH₂)₆CH₃	0	59	54	67	38	42
2h	H	(CH₂)₇CH₃	0	51	48	38	0	57
2i	H	(CH₂)₈CH₃	0	46	54	33	0	0
2j	2-Cl	CH₂CH₃	0	59	54	43	34	58
2k	4-Cl	CH₂CH₃	52	89	69	65	44	40
2l	2-Br	CH₂CH₃	35	63	57	49	64	72
2m	4-Br	CH₂CH₃	0	76	42	52	40	38
2n	2-Me	CH₂CH₃	43	71	57	58	53	82
2o	4-Me	CH₂CH₃	0	72	46	65	50	47
2p	2-OMe	CH₂CH₃	96	85	92	100	100	82
2q	4-OMe	CH₂CH₃	39	79	62	67	71	69
2r	4-Cl	(CH₂)₂CH₃	43	89	72	59	50	63
2s	4-F	(CH₂)₄CH₃	0	64	62	77	58	67
2t	4-Br	(CH₂)₄CH₃	30	83	73	66	58	65
2u	4-Cl	(CH₂)₅CH₃	70	64	67	74	47	58
2v	4-Me	(CH₂)₅CH₃	26	63	66	71	63	71
2w	4-NO₂	CH₂CH₃	0	0	0	36	0	0
2x	4-NO₂	(CH₂)₄CH₃	30	77	68	27	0	0
A16			0	48	50	45	51	—
多氧霉素B			63	83	57	63	77	70

测试菌种	Compd.	EC₅₀/(μg•L^–1)	Y曲线	r
水稻纹枯病菌	2p	2.07	Y=0.755X+4.761	0.9762
水稻纹枯病菌	多氧霉素B	15.33	Y=1.941X+2.699	0.9980
黄瓜灰霉病菌	2a	1.77	Y=0.897X+4.777	0.9990
	2p	18.85	Y=0.806X+3.972	0.9935
	多氧霉素B	3.08	Y=1.033X+4.496	0.9670
小麦赤霉病菌	2p	26.49	Y=1.107X+3.417	0.9864
小麦赤霉病菌	多氧霉素B	44.66	Y=1.091X+3.200	0.9985

测试菌种	Compd.	EC₅₀/(μg•L^–1)	Y曲线	r
水稻纹枯病菌	2p	2.07	Y=0.755X+4.761	0.9762
水稻纹枯病菌	多氧霉素B	15.33	Y=1.941X+2.699	0.9980
黄瓜灰霉病菌	2a	1.77	Y=0.897X+4.777	0.9990
	2p	18.85	Y=0.806X+3.972	0.9935
	多氧霉素B	3.08	Y=1.033X+4.496	0.9670
小麦赤霉病菌	2p	26.49	Y=1.107X+3.417	0.9864
小麦赤霉病菌	多氧霉素B	44.66	Y=1.091X+3.200	0.9985

Compd.	R¹	R²	抑制效果/%
Compd.	R¹	R²	40 μg•mL^–1	100 μg•mL^–1
2a	H	CH₃	37	67
2p	2-OMe	CH₂CH₃	69	80
2t	4-Br	(CH₂)₄CH₃	58	83
A16			47	79
尼克霉素Z			52	86

新型缩氨基硫脲类化合物的设计、合成及杀菌活性研究

Design, Synthesis and Fungicidal Actiνity of Noνel Thiosemicarbazide Compounds

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 10

References 19

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[2]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[3]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[4]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[5]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[6]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[7]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[8]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[9]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[10]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[11]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[12]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[13]	Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.
[14]	Huanqing Li, Zhaohua Chen, Zujia Chen, Qiwen Qiu, Youcai Zhang, Sihong Chen, Zhaoyang Wang. Research Progress in Mercury Ion Fluorescence Probes Based on Organic Small Molecules [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3067-3077.
[15]	Ran Zhou, Chunmei Yuan, Tao Zhang, Piao Mao, Yi Liu, Kaini Meng, Hui Xin, Wei Xue. Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3196-3209.