Synthesis and Biological Activities of Novel 8-((3,4,4-Trifluorobut-3-en-1-yl)thio)-substituted Methylxanthines and Their Derivatives

doi:10.6023/cjoc202012006

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (5): 2091-2098.DOI: 10.6023/cjoc202012006 Previous Articles Next Articles

NOTES

8-[(3,4,4-三氟丁-3-烯-1-基)硫基]取代的新型甲基黄嘌呤及其衍生物的合成和生物活性

刘航¹, 张舒昀¹, 李欢¹, 张燕¹, 李正名¹, 王宝雷¹^,^*()

1 南开大学化学学院元素有机化学国家重点实验室天津 300071

收稿日期:2020-12-01 修回日期:2020-12-31 发布日期:2021-02-22
通讯作者: 王宝雷
基金资助:
国家自然科学基金(21772103); 国家自然科学基金(22077070)

Synthesis and Biological Activities of Novel 8-((3,4,4-Trifluorobut-3-en-1-yl)thio)-substituted Methylxanthines and Their Derivatives

Hang Liu¹, Shuyun Zhang¹, Huan Li¹, Yan Zhang¹, Zhengming Li¹, Baolei Wang¹^,^*()

1 State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071

Received:2020-12-01 Revised:2020-12-31 Published:2021-02-22
Contact: Baolei Wang
About author:
* Corresponding author. E-mail: nkwbl@nankai.edu.cn
Supported by:
National Natural Science Foundation of China(21772103); National Natural Science Foundation of China(22077070)

1. 212091S.pdf(1752KB)

Abstract

Using 8-chlorotheophylline and 4-bromo-1,1,2-trifluorobut-1-ene as materials, a series of novel 8-((3,4,4-tri- fluorobut-3-en-1-yl)thio)-substituted methylxanthines and their derivatives were successfully synthesized through nucleophilic substitution, protection, deprotection, and oxidation. The structures of the title compounds were confirmed and characterized by melting point, ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Their preliminary bioassay results showed that most of the compounds in this series have good insecticidal activity. Among them, 1,3,7-trimethyl-8-((3,4,4-trifluorobut-3-en-1-yl)thio)- 3,7-dihydro-1H-purine-2,6-dione (5a), 7-isobutyl-1,3-dimethyl-8-((3,4,4-trifluorobut-3-en-1-yl)thio)-3,7-dihydro-1H-purine- 2,6-dione (5c) and 7-isobutyl-1,3-dimethyl-8-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-3,7-dihydro-1H-purine-2,6-dione (5h) had 70% lethality rate against Mythimna separata Walker at a concentration of 200 mg?L^–1. 5a, 5c and 1,3,7-trimethyl- 8-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-3,7-dihydro-1H-purine-2,6-dione (5f) exhibited lethality rates of 72%, 80% and 65% against Plutella xylostellaL. at a concentration of 10 mg?L^–1, respectively. Some of the compounds also showed certain fungicidal activity at 50 mg?L^–1, among which 7-(cyclopropylmethyl)-1,3-dimethyl-8-((3,4,4-trifluorobut-3-en-1-yl)thio)-3,7- dihydro-1H-purine-2,6-dione (5b) possessed inhibition rates of 66.7% and 61.1% against Phytophthora capsici and Botrytis cinerea, respectively. 5c held a 55.6% inhibition rate towards Botrytis cinerea. This type of compounds provides new lead structures for the further research and development of novel insecticides.

Key words: 8-substituted methylxanthine derivative, synthesis, insecticidal activity, fungicidal activity, structure-activity relationship

Cite this article

Hang Liu, Shuyun Zhang, Huan Li, Yan Zhang, Zhengming Li, Baolei Wang. Synthesis and Biological Activities of Novel 8-((3,4,4-Trifluorobut-3-en-1-yl)thio)-substituted Methylxanthines and Their Derivatives[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 2091-2098.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

References 32

[1]	Shang, E.-C. Mod. Agrochem. 2009, 8, 1. (in Chinese).
	(尚尔才, 现代农药, 2009, 8, 1.)
[2]	Chen, W.-Y. Research and Development of New Pesticides―Methods and Progress, Chemical Industry Press, Beijing, 2007, pp.20~21. (in Chinese).
	(陈万义主编, 新农药的研发――方法•进展, 化学工业出版社, 北京, 2007, pp.20~21.)
[3]	Amirkia, V.; Heinrich, M. Phytochem. Lett. 2014, 10, xlviii.
[4]	Rabe, K. F.; Magnussen, H.; Dent, G. Eur. Respir. J. 1995, 8, 637. pmid: 7664866
[5]	(a) Qi, L.-Y.; Li, T.; Tang, X.-F. China Prac. Med. 2020, 15, 128. (in Chinese).
	(戚良燕, 李婷, 唐小飞, 中国实用医药, 2020, 15, 128.)
	(b) Benfey, B. G. Br. J. Pharmacol. 1977, 59, 75. doi: 10.1111/bph.1977.59.issue-1
[6]	Ward, A.; Clissold, S. P. Drugs 1987, 34:50. pmid: 3308412
[7]	van Mastbergen, J.; Jolas, T.; Allegra, L.; Page, C. P. Pulm. Pharmacol. Ther. 2012, 25, 55. doi: 10.1016/j.pupt.2011.10.007 pmid: 22138191
[8]	Bondan, E. F.; Monteiro Martins, M. D. F.; Bernardi, M. M. Arch. Endocrinol. Metab. 2015, 59, 47. doi: 10.1590/2359-3997000000009
[9]	Foukas, L. C.; Daniele, N.; Ktori, C.; Anderson, K. E.; Jensen, J.; Shepherd, P. R. J. Biol. Chem. 2002, 277, 37124. doi: 10.1074/jbc.M202101200
[10]	Kakuyama, A.; Sadzuka, Y. Curr. Drug Metab. 2001, 2, 379. pmid: 11766989
[11]	Schmitt, M.; Turberg, A.; Londershausen, M.; Dorn, A. Pestic. Sci. 1996, 48, 375. doi: 10.1002/(SICI)1096-9063(199612)48:4【-逻辑与-】amp;lt;【-逻辑与-】amp;gt;1.0.CO;2-F
[12]	Zhou, D.-S.; Long, J.-M. Jiangsu Agric. Sci. 2015, 43, 119. (in Chinese).
	(周东升, 龙九妹, 江苏农业科学, 2015, 43, 119.)
[13]	Gressel, J. Pest Manage. Sci. 2018, 74, 511. doi: 10.1002/ps.2018.74.issue-3
[14]	Yu, Y. Biol. Teach. 2011, 36, 57. (in Chinese).
	(余轶, 生物学教学, 2011, 36, 57.)
[15]	Balieira, K. V. B.; Mazzo, M.; Bizerra, P. F. V.; Guimares, A. R. D. S.; Nicodemo, D.; Mingatto, F. E. Apidologie 2018, 49, 562. doi: 10.1007/s13592-018-0583-1
[16]	Ando, W. Sulfur Rep. 1981, 1, 147.
[17]	(a) Sarmah, A. K.; Sabadie, A. J. J. Agric. Food Chem. 2002, 50, 6253. doi: 10.1021/jf025575p
	(b) Huang, J.; Ayad, H. M.; Timmons, P. R. US 5360910, 1994.
	(c) Timmons, P.; Outcalt, R.; Cramp, S.; Kwiatkowski, P.; Lopes, A.; Sinodis, D.; Cain, P. EP 372982, 1990.
	(d) Mathre, D. E. J. Agric. Food Chem. 1971, 19, 869. doi: 10.1021/jf60177a040
[18]	Jeanguenat, A.; O'Sullivan, A. C. WO 2006032462, 2006.
[19]	Loiseleur, O.; Slaats, B.; Maeinfish, P. In Modern Crop Protection Compounds, Eds.: Krämer, W.; Schirmer, U.; Jeschke, P.; Witschel, M.,Wiley-VCH, Weinheim, 2012, pp.1367~1387.
[20]	Kearn, J.; Ludlow, E.; Dillon, J.; O'Connor, V.; Holden-Dye, L. Pestic. Biochem. Physiol. 2014, 109, 44. doi: 10.1016/j.pestbp.2014.01.004
[21]	Yang, S.; Yasgar. A.; Mille. B.; Lal-Nag, M.; Brimacombe, K..; Hu, X.; Sun, H. M.; Wang, A.; Xu, X.; Nguyen, K.; Oppermann, Udo.; Ferrer, M.; Vasiliou, V.; Simeonov A.; Jadhav, A.; Maloney, D. J. J. Med. Chem. 2015, 58, 5967. doi: 10.1021/acs.jmedchem.5b00577
[22]	Yan, B.; Liu, L.; Huang, S.; Ren, Y.; Wang, H.; Yao, Z.; Li, L.; Chen, S.; Wang, X.; Zhang, Z.; Chem. Commun. 2017, 53, 3637. doi: 10.1039/C7CC00667E
[23]	Dastbaravardeh, N.; Kirchner, K.; Schnürch, M.; Mihovilovic, M. D. J. Org. Chem. 2013, 78, 658. doi: 10.1021/jo302547q
[24]	Xie, Y.; Zhou, B.; Zhou, S.; Zhou, S.; Wei, W.; Liu, J.; Zhan, Y.; Cheng, D.; Chen, M.; Li, Y.; Wang, B.; Xue, X.; Li, Z. ChemistrySelect 2017, 2, 1620. doi: 10.1002/slct.201700132
[25]	Kalla, R. V.; Elzein, E.; Perry, T.; Li, X.; Palle, V.; Varkhedkar, V.; Gimbel, A.; Maa, T.; Zeng, D.; Zablocki, J. J. Med. Chem. 2006, 49, 3682. pmid: 16759111
[26]	Gusmeroli, M.; D'Orazio, G.; Forgia, D.; Bellandi, P.; Sargiotto, C.; Bianchi, D. WO 2020075107, 2020.
[27]	Strydom, B.; Malan, S. F.; Castagnoli Jr., N.; Bergh, J. J.; Petzer, J. P. Bioorg. Med. Chem. 2010, 18, 1018. doi: 10.1016/j.bmc.2009.12.064
[28]	Blicke, F. F.; Schaaf, R. L. J. Am. Chem. Soc. 1956, 78, 5857. doi: 10.1021/ja01603a041
[29]	Wang, B.-L.; Zhu, H.-W.; Ma, Y.; Xiong, L.-X.; Li, Y.-Q.; Zhao, Y.; Zhang, J.-F.; Chen, Y.-W.; Zhou, S.; Li, Z.-M. J. Agric. Food Chem. 2013, 61, 5483. doi: 10.1021/jf4012467
[30]	Wang, B.; Wang, H.; Liu, H.; Xiong, L.; Yang, N.; Zhang, Y.; Li, Z. Chin. Chem. Lett. 2020, 31, 739. doi: 10.1016/j.cclet.2019.07.064
[31]	Wang, B.-L.; Zhu, H.-W.; Li, Z.-M.; Wang, L.-Z.; Zhang, X.; Xiong, L.-X.; Song, H.-B. Pest Manage. Sci. 2018, 74, 726. doi: 10.1002/ps.2018.74.issue-3
[32]	Sun, N.; Shen, Z.; Zhai, Z.; Han, L.; Weng, J.; Tan, C.; Liu, X. Chin. J. Org. Chem. 2017, 37, 2705. (in Chinese).
	(孙娜波, 沈钟华, 翟志文, 韩亮, 翁建全, 谭成侠, 刘幸海, 有机化学, 2017, 37, 2705.) doi: 10.6023/cjoc201704032

Compd.	杀虫活性/%
	东方粘虫	小菜蛾				番茄早疫病菌	辣椒疫霉病菌	油菜菌核病菌	黄瓜灰霉病菌	苹果轮纹病菌	小麦纹枯病菌
		200 mg/L	200 mg/L	100 mg/L		番茄早疫病菌	辣椒疫霉病菌	油菜菌核病菌	黄瓜灰霉病菌	苹果轮纹病菌	小麦纹枯病菌	10 mg/L
5a	70		100	90	72	28.6	23.8	39.1	38.9	54.7	43.0
5b	50		80	40	NT ^a	28.6	66.7	60.9	61.1	47.2	54.4
5c	70		100	90	80	42.9	61.9	60.9	55.6	45.3	60.8
5d	55		45	NT	NT	14.3	9.5	13.0	38.9	32.1	22.8
5e	15		67	NT	NT	7.1	19.0	8.7	16.7	37.7	29.1
5f	60		100	85	65	7.1	23.8	21.7	16.7	34.0	29.1
5g	50		100	75	NT	7.1	9.5	30.4	27.8	32.1	31.6
5h	70		100	67	NT	14.3	14.3	21.7	38.9	20.8	27.8
5i	50		65	NT	NT	7.1	14.3	8.7	33.3	49.1	35.4
5j	30		90	60	NT	7.1	9.5	17.4	33.3	54.7	29.1
C-1^b	65		88	55	NT	28.6	28.6	30.4	33.3	69.8	60.8
C-2^c	NT		NT	NT	NT	100.0	66.7	100.0	50.0	94.3	84.8
C-3^d	NT		NT	NT	NT	57.1	100.0	100.0	100.0	88.7	73.4

Compd.	杀虫活性/%
	东方粘虫	小菜蛾				番茄早疫病菌	辣椒疫霉病菌	油菜菌核病菌	黄瓜灰霉病菌	苹果轮纹病菌	小麦纹枯病菌
		200 mg/L	200 mg/L	100 mg/L		番茄早疫病菌	辣椒疫霉病菌	油菜菌核病菌	黄瓜灰霉病菌	苹果轮纹病菌	小麦纹枯病菌	10 mg/L
5a	70		100	90	72	28.6	23.8	39.1	38.9	54.7	43.0
5b	50		80	40	NT ^a	28.6	66.7	60.9	61.1	47.2	54.4
5c	70		100	90	80	42.9	61.9	60.9	55.6	45.3	60.8
5d	55		45	NT	NT	14.3	9.5	13.0	38.9	32.1	22.8
5e	15		67	NT	NT	7.1	19.0	8.7	16.7	37.7	29.1
5f	60		100	85	65	7.1	23.8	21.7	16.7	34.0	29.1
5g	50		100	75	NT	7.1	9.5	30.4	27.8	32.1	31.6
5h	70		100	67	NT	14.3	14.3	21.7	38.9	20.8	27.8
5i	50		65	NT	NT	7.1	14.3	8.7	33.3	49.1	35.4
5j	30		90	60	NT	7.1	9.5	17.4	33.3	54.7	29.1
C-1^b	65		88	55	NT	28.6	28.6	30.4	33.3	69.8	60.8
C-2^c	NT		NT	NT	NT	100.0	66.7	100.0	50.0	94.3	84.8
C-3^d	NT		NT	NT	NT	57.1	100.0	100.0	100.0	88.7	73.4

8-[(3,4,4-三氟丁-3-烯-1-基)硫基]取代的新型甲基黄嘌呤及其衍生物的合成和生物活性

Synthesis and Biological Activities of Novel 8-((3,4,4-Trifluorobut-3-en-1-yl)thio)-substituted Methylxanthines and Their Derivatives

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 32

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	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.
[2]	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.
[3]	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.
[4]	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.
[5]	Haibo Huo, Guixia Li, Shijun Wang, Chun Han, Baojun Shi, Jian Li. Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 204-215.
[6]	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.
[7]	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.
[8]	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.
[9]	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.
[10]	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.
[11]	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.
[12]	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.
[13]	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.
[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.