新型1,3,4-噻二唑并[3,2-a]嘧啶酮类介离子衍生物的合成及其生物活性
收稿日期: 2019-03-13
修回日期: 2019-04-05
网络出版日期: 2019-04-16
基金资助
国家重点研发计划（No.2018YFD0200100）资助项目.
Synthesis and Biological Activity of Novel 1,3,4-Thiadiazolo[3,2-a]pyrimidinone Mesoionic Derivatives
Received date: 2019-03-13
Revised date: 2019-04-05
Online published: 2019-04-16
Supported by
Project supported by the National Key Research and Development Program of China (No. 2018YFD0200100).
以三氟苯嘧啶为先导化合物，设计并合成了一系列结构新颖的1，3，4-噻二唑并[3，2-a]嘧啶酮类介离子衍生物.利用1H NMR，13C NMR，19F NMR和HRMS对其进行结构表征.初步生物活性表明，多数化合物在100 μg/mL浓度下表现出一定的杀虫活性，其中2-（（4-溴苄基）硫基）-8-（（2-氯噻唑-5-基）甲基）-5-氧代-6-（3-（三氟甲基）苯基）-5H-[1，3，4]噻二唑并[3，2-a]嘧啶-8-鎓-7-盐（8b）和2-（（（2-氯噻唑-5-基）甲基）硫基）-8-（（2-氯噻唑-5-基）甲基）-5-氧代-6-（3-（三氟甲基）苯基）-5H-[1，3，4]噻二唑并[3，2-a]嘧啶-8-鎓-7-盐（8d）对白背飞虱（white-backed planthopper，WBPH）的致死率均为70%；此外，部分化合物在浓度为50 μg/mL时对水稻白叶枯病菌（Xanthomonas oryzae pv. oryzae，Xoo），水稻细菌性条斑病菌（Xanthomonas oryzae pv. oryzicola，Xoc）和柑橘溃疡病菌（Xanthomonas citri pv. citri，Xcc）表现出较好的抑抗菌性，其中2-（（2-（三氟甲基）苄基）硫基）-8-（（2-氯噻唑-5-基）甲基）-5-氧代-6-（3-（三氟甲基）苯基）-5H-[1，3，4]噻二唑并[3，2-a]嘧啶-8- 鎓-7-盐（8h）对水稻白叶枯病菌和水稻细菌性条斑病菌的抑制率分别为70.91%和53.34%，均优于对照药剂三氟苯嘧啶（42.85%和51.22%）、噻菌铜（47.76%和23.25%）和叶枯唑（66.97%和17.24%）；2-（（3-（三氟甲基）苄基）硫基）-8-（（2-氯噻唑-5-基）甲基）-5-氧代-6-（3-（三氟甲基）苯基）-5H-[1，3，4]噻二唑并[3，2-a]嘧啶-8-鎓-7-盐（8e）对柑橘溃疡病菌的抑制率为68.97%，优于噻菌铜（35.85%）和叶枯唑（37.53%）.
关键词： 介离子; 1,3,4-噻二唑并[3,2-a]嘧啶酮; 杀虫活性; 抑菌活性
何文静 , 刘登曰 , 甘秀海 , 张建 , 刘峥军 , 易崇粉 , 宋宝安 . 新型1,3,4-噻二唑并[3,2-a]嘧啶酮类介离子衍生物的合成及其生物活性[J]. 有机化学, 2019 , 39(8) : 2287 -2294 . DOI: 10.6023/cjoc201903023
A series of 1,3,4-thiadiazolo[3,2-a]pyrimidinone mesoionic derivatives were designed and synthesized with triflumezopyrim as the leading compound, and their structures were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary biological activities indicated that the target compounds showed certain insecticidal activities at 100 μg/mL, of which the lethality rates of 2-((4-chlorobenzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phen-yl)-5H-[1,3,4]-thiadiazolo[3,2-a]pyrimidin-8-ium-7-olate (8b) and 2-(((2-chlorothiazol-5-yl)methyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1,3,4]thiadiazolo-[3,2-a]pyrimidin-8-ium-7-olate (8d) against white-backed planthopper (WBPH) were 70%. Some compounds showed good antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas citri pv. citri (Xcc) at 50 μg/mL, and the inhi-bitory rates of 2-((2-(trifluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-8-ium-7-olate (8h) to Xoo and Xoc were 70.91% and 53.34%, respectively, which were better than thiodiazole copper (47.76% and 23.25%) and bismerthiazol (66.97% and 17.24%). The inhibition rate of 2-((3-(tri-fluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1,3,4]thiadiazolo[3,2-a]-pyrimidin-8-ium-7-olate (8e) to Xcc was 68.97%, which was better than thiediazole copper (35.85%) and bismerthiazol (37.53%)
[1] Earl, J. C.; Mackney, A. W. J. Chem. Soc. 1935. 899-900.
[2] Miao, Q.; Sun, H. L. Chin. Sci. Bull. 2015, 60, 2003(in Chinese). (苗群,孙怀林,科学通报, 2015, 60, 2003.)
[3] Ren, X. M.S. Thesis, East China Normal University, Shanghai, 2015(in Chinese). (任晓,硕士论文,华东师范大学,上海, 2015.)
[4] Ollis, W. D.; Ramsden, C. A. Adv. Heterocycl. Chem. 1976, 19, 1.
[5] Latthe, P. R.; Shinge, P. S.; Badami, B. V.; Patil, P. B.; Holihosur, S. N. J. Chem. Sci. 2006, 118, 249.
[6] Huisgen, R.; Gotthardt, H.; Bayer, H. O. Angew. Chem., Int Ed. 1964, 3, 136.
[7] Gotthardt, H.; Huisgen, R.; Schaefer, F. C. Tetrahedron Lett. 1964, 10, 487.
[8] Coburn, R. A.; Glennon, R. A. J. Pharm. Sci. 1973, 62, 1785.
[9] Coburn, R. A.; Carapellotti, R. A. J. Pharm. Sci. 1976, 65, 1505.
[10] White, E. H.; Egger, N. J. Am. Chem. Soc. 1984, 106, 3701.
[11] Chandrasekhar, R.; Nanjan, M. J. Mini. Rev. Med. Chem. 2012, 12, 1359.
[12] Jogul, J. J.; Badami, B. V. J. Serb. Chem. Soc. 2006, 71, 851.
[13] Holyoke Jr, C. W.; Zhang, W. M; Pahutski, T. F., Jr.; Lahm, G. P.; Tong, M. H. T.; Cordova, D.; Leighty, R. M. ACS Symposium Series, American Chemical Society, Washington, DC, U. S. A., 2015, pp. 365~378.
[14] Zhang, W. M.; Holyoke, C. W.; Barry, J.; Leighty, R. M.; Cordova, D.; Vincent, D. R.; Briddell, T. A. Bioorg. Med. Chem. Lett. 2016, 26, 5444.
[15] Zhang, W. M. Acc. Chem. Res. 2017, 50, 2381.
[16] Holyoke Jr, C. W.; Cordova, D.; Zhang, W. M.; Barry, D. J.; Leighty, M. R.; Dietrich, F. R.; Rauh, J. J.; Pahutski, F. T. Jr.; Lahm, P. G.; Tong, T. M.-H.; Benner, A. E.; Andreassi, L. J.; Smith, M. R.; Vincent, R. D.; Christianson, A. L.; Teixeira, A. L.; Singh, V.; Hughes, A. K. Pest Manage. Sci. 2017, 73, 796.
[17] Zhang, W. M.; Holyoke Jr, C. W.; Pahutski, F. T. Jr.; Lahm, P. G.; Barry, D. J.; Cordova, D.; Leighty, M. R.; Singh, V.; Vincent, R. D.; Tong, T. M.-H.; Hughes, A. K.; McCann, F. S.; Henry, T. Y.; Xu, M.; Briddell, A. T. Bioorg. Med. Chem. Lett. 2017, 27, 16.
[18] Zhang, W. M.; Holyoke, W. C. Jr.; Barry, J.; Cordova, D.; Leighty, M. R.; Tong, T. M.-H.; Hughes, A. K.; Lahm, P. G.; Pahutski, F. T. Jr.; Xu, M.; Briddell, A. T.; McCann, F. T.; Henry, T. Y.; Chen, Y. Z. Bioorg. Med. Chem. Lett. 2017, 27, 911.
[19] Cordova, D.; Benner, A. E.; Schroeder, E. M.; Holyoke, W. C. Jr.; Zhang, W. M.; Pahutski, F. T. Jr.; Leighty, M. R.; Vincent, R. D.; Hamm, C. J. Insect. Biochem. Mol. Biol. 2016, 74, 32.
[20] Narine, A.; Dickhaut, J.; Kaiser, F.; Bandur, N. G.; Koerber, K.; Von Deyn, W.; Derksen, S.; Paulini, R.; Culbertson, D. L. WO 201314428, 2013[Chem. Abstr. 2013, 1548107].
[21] Dickhaut, J.; Narine, A.; Derksen, S.; Bandur, N. G.; Von Deyn, W.; Koller, R.; Wach, J.-Y.; Langewald, J.; Rankl, N. B. WO 2014202582, 2014[Chem. Abstr. 2014, 2127280].
[22] Narine, A.; Bandur, N. G.; Dickhaut, J.; Derksen, S.; Koller, R.; Von Deyn, W.; Wach, J.-Y.; Culbertson, D. L. WO 2014167084, 2014[Chem. Abstr. 2014, 1752875].
[23] Narine, A.; Dickhaut, J.; Kaiser, F.; Bandur, N. G.; Koerber, K.; Von Deyn, W. WO 2014033244, 2014[Chem. Abstr. 2014, 353348].
[24] Dickhaut, J.; Narine, A.; Von Deyn, W.; Koller, R.; Wach, J.-Y.; Vyas, D.; Adisechan, A.; Shinde, H. WO 2016055431, 2016[Chem. Abstr. 2016, 588392].
[25] Hasegawa, S.; Kamo, T.; Kagohara, Y.; Miyake, T.; Kobayashi, T.; Matsuda, R.; Asano, S.; Kudamatsu, A. WO 2016171053, 2016[Chem. Abstr. 2016, 1739385].
[26] Pan, J. K.; Yu, L.; Liu, D. Y.; Hu, D. Y. Molecules 2018, 23, 1217.
[27] Chen, X. W.; Gan, X. H.; Chen, J. X.; Chen, Y. Z.; Wang, Y. J.; Hu, D. Y.; Song, B. A. Chin. J. Org. Chem. 2017, 37, 2343(in Chinese). (陈学文,甘秀海,陈吉祥,陈永中,王艳娇,胡德禹,宋宝安,有机化学, 2017, 37, 2343.)
[28] Wang, B. L.; Zhu, H. W.; Li, Z. M.; 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.
[29] Wang, Y. H.; Yang L.; Liu, Z. C. Chin. J. Org. Chem. 2013, 33, 154(in Chinese). (王应红,杨录,刘志昌,有机化学, 2013, 33, 154.)
[30] Gan, X. H.; Cheng, Z.; Wang, Y. J.; Hu, D. Y.; Song, B. A. Bioorg. Med. Chem. Lett. 2017, 27, 4298.
[31] Jin, G. Y.; Hou, Z.; Zhao, G. F.; Cao, C. Y.; Li, Y. C. Chem. J. Chin. Univ. 1997, 18, 409(in Chinese). (金桂玉,侯震,赵国峰,曹春阳,李煜昶,高等学校化学学报, 1997, 18, 409.)
[32] Knerr, P. J.; Tzekou. A.; Ricklin, D.; Qu, H. C.; Chen, H.; Donk, W. A.; Lambris, J. D. ACS Chem. Biol. 2011, 15, 753.
[33] Xu, W. M.; Li, S. Z.; He, M.; Yang, S. Li, X. Y.; Li, P. Bioorg. Med. Chem. Lett. 2013, 23, 5821.
[34] Lei, G. Y.; Ying, J. W.; Liu, C.; L.; Luo, H.; Song, Y. Q.; Yang, H. B.; Li, B. Modern Agrochem. 2016, 15, 5(in Chinese). (雷光月,英君伍,刘成利,罗焕,宋玉泉,杨辉斌,李斌,现代农药, 2016, 15, 5.)
[35] Holyoke, W. C. Jr.; Tong, T. M.-H.; Zhang, W. M. WO 2012106495, 2012[Chem. Abstr. 2012, 1158736].
[36] Wang, X.; Li, P.; Li, Z. M.; Yin, J.; He, M.; Xue, W.; Chen, Z.; Song, B. A. J. Agric. Food Chem. 2013, 61, 9575.
/
| 〈 |
|
〉 |
