• 百种中国杰出学术期刊
  • 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国高校精品科技期刊
  • 中国国际影响力优秀学术期刊
  • 中国科技核心期刊

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

新型三唑哌嗪类衍生物的合成及生物活性

邓珅钏 李旭军 朱祥 杜晓英 李俊凯 徐志红

邓珅钏, 李旭军, 朱祥, 杜晓英, 李俊凯, 徐志红. 新型三唑哌嗪类衍生物的合成及生物活性[J]. 农药学学报, 2021, 23(2): 269-278. doi: 10.16801/j.issn.1008-7303.2021.0009
引用本文: 邓珅钏, 李旭军, 朱祥, 杜晓英, 李俊凯, 徐志红. 新型三唑哌嗪类衍生物的合成及生物活性[J]. 农药学学报, 2021, 23(2): 269-278. doi: 10.16801/j.issn.1008-7303.2021.0009
Shenchuan DENG, Xujun LI, Xiang ZHU, Xiaoying DU, Junkai LI, Zhihong XU. Synthesis and biological activities of novel triazole piperzazine derivatives[J]. Chinese Journal of Pesticide Science, 2021, 23(2): 269-278. doi: 10.16801/j.issn.1008-7303.2021.0009
Citation: Shenchuan DENG, Xujun LI, Xiang ZHU, Xiaoying DU, Junkai LI, Zhihong XU. Synthesis and biological activities of novel triazole piperzazine derivatives[J]. Chinese Journal of Pesticide Science, 2021, 23(2): 269-278. doi: 10.16801/j.issn.1008-7303.2021.0009

新型三唑哌嗪类衍生物的合成及生物活性

doi: 10.16801/j.issn.1008-7303.2021.0009
基金项目: 国家自然科学基金 (31772170)
详细信息
    作者简介:

    邓珅钏,女,硕士研究生,E­mail:907671295@qq.com

    通讯作者:

    徐志红,通信作者 (Author for correspondence),男,副教授,主要从事农药学的教学与研究工作,E­mailx_u_78@sina.com

  • 中图分类号: O626.26;TQ450.11

Synthesis and biological activities of novel triazole piperzazine derivatives

  • 摘要: 以1,2,4-三唑、2-氯-2,4-二氟苯乙酮和哌嗪为原料,通过活性亚结构拼接合成了一个系列20个新型三唑哌嗪类衍生物 7a ~ 7t ,其结构均经过了1H NMR、13C NMR和高分辨质谱确证。分别采用菌丝生长速率法和触杀法测定了目标化合物的杀菌活性和杀虫活性。杀菌活性测定结果显示:大部分化合物对小麦赤霉病菌、水稻纹枯病菌和水稻稻瘟病菌具有良好的抑制作用,在200 μmol/L下,化合物 7n7r7s 对小麦赤霉病菌的抑制率分别为60.19%、62.27%和50.00%,与对照药剂三唑酮抑菌效果相当;化合物 7r 对水稻纹枯病菌的EC50值为49.49 μmol/L。杀虫活性测定结果显示,在100 mg/L时,化合物 7o 对斜纹夜蛾幼虫的致死率为40.00%,略低于对照药剂氰氟虫腙 (46.67%)。本研究所合成的新化合物兼具杀菌和杀虫活性,可为新型三唑哌嗪类衍生物的生物活性研究提供参考。
  • 1  目标化合物的合成路线

    1.  Synthetic route of target compounds

    表  1  目标化合物对6种植物病原菌菌丝生长的抑制作用

    Table  1.   Inhibitory effect of target compounds against six pathogenic fungi in vitro

    化合物
    Compd.
    抑制率 Inhibition rate/%
    水稻纹枯病菌
    R. solani
    小麦赤霉病菌
    F. graminearm
    番茄早疫病菌
    A. solani
    水稻稻瘟病菌
    M. oryzae
    白芨白绢病菌
    S. rolfii
    西瓜枯萎病菌
    F. oxysporum
    7a 52.94 ± 0.02 16.20 ± 0.07 3.03 ± 0.02 24.17 ± 0.02 17.25 ± 0.02 3.13 ± 0.01
    7b 53.21 ± 0.02 11.82 ± 0.03 3.73 ± 0.03 18.15 ± 0.02 11.53 ± 0.01 1.14 ± 0.03
    7c 53.29 ± 0.03 21.81 ± 0.01 4.08 ± 0.00 26.68 ± 0.01 9.97 ± 0.00 2.07 ± 0.02
    7d 48.06 ± 0.00 8.54 ± 0.01 1.96 ± 0.01 20.32 ± 0.01 5.21 ± 0.03 0.06 ± 0.02
    7e 43.98 ± 0.01 21.28 ± 0.01 5.74 ± 0.01 25.76 ± 0.02 12.28 ± 0.00 1.80 ± 0.01
    7f 52.31 ± 0.03 7.08 ± 0.03 5.94 ± 0.01 26.13 ± 0.01 10.48 ± 0.01 5.59 ± 0.02
    7g 44.55 ± 0.02 5.50 ± 0.01 4.53 ± 0.01 22.38 ± 0.01 7.16 ± 0.03 4.37 ± 0.03
    7h 52.11 ± 0.05 13.27 ± 0.03 3.60 ± 0.01 25.74 ± 0.02 8.87 ± 0.03 8.25 ± 0.08
    7i 47.02 ± 0.08 11.42 ± 0.01 1.52 ± 0.02 21.10 ± 0.01 1.61 ± 0.01 10.33 ± 0.01
    7j 60.17 ± 0.02 1.76 ± 0.01 1.30 ± 0.01 23.71 ± 0.01 8.13 ± 0.01 0.40 ± 0.01
    7k 52.70 ± 0.03 20.48 ± 0.02 5.87 ± 0.01 31.33 ± 0.02 12.92 ± 0.00 6.58 ± 0.01
    7l 64.59 ± 0.01 23.29 ± 0.03 3.82 ± 0.00 29.06 ± 0.02 14.79 ± 0.03 8.29 ± 0.06
    7m 52.10 ± 0.02 32.75 ± 0.01 8.78 ± 0.02 46.68 ± 0.01 16.58 ± 0.02 7.08 ± 0.02
    7n 68.23 ± 0.02 60.19 ± 0.01 22.00 ± 0.09 36.71 ± 0.00 12.15 ± 0.02 7.86 ± 0.00
    7o 52.37 ± 0.03 17.05 ± 0.05 5.99 ± 0.01 35.11 ± 0.01 18.41 ± 0.03 4.92 ± 0.01
    7p 51.21 ± 0.00 17.88 ± 0.02 7.78 ± 0.03 41.51 ± 0.03 0.05 ± 0.03 4.92 ± 0.02
    7q 56.87 ± 0.01 47.72 ± 0.03 12.51 ± 0.01 30.91 ± 0.01 20.19 ± 0.07 12.31 ± 0.04
    7r 60.64 ± 0.01 62.27 ± 0.02 16.38 ± 0.00 40.00 ± 0.01 9.30 ± 0.02 10.41 ± 0.05
    7s 60.06 ± 0.01 50.00 ± 0.02 17.41 ± 0.01 43.18 ± 0.01 16.57 ± 0.02 15.70 ± 0.03
    7t 56.06 ± 0.04 38.97 ± 0.05 9.09 ± 0.01 23.39 ± 0.02 10.43 ± 0.02 10.71 ± 0.05
    三唑酮 triazolone 90.17 ± 0.01 62.61 ± 0.07 39.85 ± 0.01 99.14 ± 0.01 99.38 ± 0.00 75.34 ± 0.02
    注:每个处理重复3次 (平均值 ± 标准差),化合物浓度为200 μmol/L。Note: Inhibition rate was measured at the concentration of 200 μmol/L. Each treatment had three replicates (Mean ± SD).
    下载: 导出CSV

    表  2  部分目标化合物对供试病原菌的EC50

    Table  2.   The EC50 values of some target compounds against test phytopathogens

    供试病原菌
    Test phytopathogen
    化合物
    Compd.
    取代基
    R
    毒力回归方程
    Toxicity regression equations
    EC50/
    (μmol/L)
    95% 置信区间
    95% Confidence interval/
    (μmol/L)
    相关系数
    r
    水稻纹枯病菌
    R. solani
    7l 3-Cl y = 0.6181x + 3.8421 74.67 65.06~85.71 0.993
    7n 4-CH(CH3)2 y = 0.5503x + 3.8671 118.0 99.39~140.0 0.989
    7r 4-C(CH3)3 y = 0.6489x + 3.9005 49.49 36.49~67.12 0.976
    7s 2,4-Cl2 y = 0.8572x + 3.3315 88.41 71.87~108.7 0.983
    三唑醇 triadimenol y = 0.8395x + 4.4524 4.49 1.17~17.24 0.940
    小麦赤霉病菌
    F. graminearm
    7n 4-CH(CH3)2 y = 1.1507x +2.5717 128.9 115.6~143.7 0.996
    7r 4-C(CH3)3 y = 0.7329x + 3.5048 109.7 87.27~137.8 0.980
    三唑醇 triadimenol y = 1.6475x +1.4079 151.5 143.4~160.1 0.999
    注:每个处理重复3次。Note: Each treatment had three replicates.
    下载: 导出CSV

    表  3  目标化合物对斜纹夜蛾的杀虫活性

    Table  3.   Insecticidal activities of target compounds against Spodoptera litura

    化合物
    Compd.
    死亡率
    Mortality/%
    化合物
    Compd.
    死亡率
    Mortality/%
    7a 10.00 7l 16.67
    7b 13.33 7m 3.33
    7c 6.67 7n 10.00
    7d 3.33 7o 40.00
    7e 20.00 7p 30.00
    7f 10.00 7q 13.33
    7g 30.00 7r 10.00
    7h 6.67 7s 13.33
    7i 3.33 7t 10.00
    7j 26.67 氰氟虫腙
    metaflumizone
    46.67
    7k 6.67
    注:每个处理重复3次, 化合物质量浓度为100 mg/L。Note: The concentration of the compound was 100 mg/mL. Each treatment had three replicates.
    下载: 导出CSV
  • [1] 王景梅, 李凌君, 张贵生. 1,2,3-三唑化合物的合成研究进展[J]. 有机化学, 2009, 29(1): 13-19.

    WANG J M, LI L J, ZHANG G S. Progress in syntheses of 1,2,3-triazoles[J]. Chinese J Org Chem, 2009, 29(1): 13-19.
    [2] HU B Y, ZHAO H Q, CHEN Z L, et al. Efficient synthesis and bioactivity of novel triazole derivatives[J]. Molecules, 2018, 23(4): 709. doi: 10.3390/molecules23040709
    [3] 毛连纲, 徐冬梅, 袁善奎, 等. 基于登记用量分析三唑类杀菌剂在中国的登记现状[J]. 农药学学报, 2020, 22(4): 586-594.

    MAO L G, XU D M, YUAN S K, et al. Analysis on the status of triazole fungicides in China based on the registered dosage[J]. Chin J Pestic Sci, 2020, 22(4): 586-594.
    [4] WANG T, MIAO W, WU S, et al. Synthesis, crystal structure, and herbicidal activities of 2-cyanoacrylates containing 1,3,4-thiadiazole moieties[J]. Chin J Chem, 2011, 29(5): 959-967. doi: 10.1002/cjoc.201190196
    [5] WAN R, ZHANG J, HAN F, et al. Synthesis and insecticidal activities of novle 1,3,4-thiadiazole 5-fluorouracil acetamidies derivatives: an RNA interference insecticide[J]. Nucleos Nucleot Nucl, 2011, 30(4): 280-292. doi: 10.1080/15257770.2011.580811
    [6] KISHOREKUMAR A, JALEEL C A, MANIVANNAN P, et al. Comparative effects of different triazole compounds on antioxidant metabolism of Solenostemon rotundifolius[J]. Colloid Surface B Biointerfaces, 2008, 62(2): 307-311. doi: 10.1016/j.colsurfb.2007.10.014
    [7] FLETCHER R A. GILLEY A, DAVIS D, et al. Triazoles as plant growth regulators and protectants[M]. Hort. Rev. 2000, 24: 55-138.
    [8] 杨双花, 翟智卫, 许良忠. 含醚键的新型三唑类化合物的合成及生物活性[J]. 农药, 2010, 49(9): 645-647, 649. doi: 10.3969/j.issn.1006-0413.2010.09.005

    YANG S H, ZHAI Z W, XU L Z. Synthesis and biological activities of novel triazole compounds containing ether link[J]. Agrochemicals, 2010, 49(9): 645-647, 649. doi: 10.3969/j.issn.1006-0413.2010.09.005
    [9] 杜琳, 张斌, 宁磊, 等. 含三唑结构的环己甲酰胺衍生物的合成及杀菌活性[J]. 农药学学报, 2020, 22(4): 595-601.

    DU L, ZHANG B, NING L, et al. Synthesis and fungicidal activity of cyclohexanamide derivatives with triazole moeity[J]. Chin J Pestic Sci, 2020, 22(4): 595-601.
    [10] 童建颖, 石延霞, 刘幸海, 等. 含邻氟苯基的1,2,4-三唑类衍生物的合成及杀菌活性研究[J]. 有机化学, 2012, 32(12): 2373-2377. doi: 10.6023/cjoc201207020

    TONG J Y, SHI Y X, LIU X H, et al. Synthesis and fungicidal activity of 1,2,4-triazole derivatives containing 2-fluorophenyl moiety[J]. Chinese J Org Chem, 2012, 32(12): 2373-2377. doi: 10.6023/cjoc201207020
    [11] 杜志明, 张英豪, 韩志跃, 等. 三唑类富氮化合物的研究进展[J]. 北京理工大学学报, 2016, 36(6): 551-557.

    DU Z M, ZHANG Y H, HAN Z Y, et al. Research progress on triazole nitogen-rich compounds[J]. Trans Beijing Inst Technol, 2016, 36(6): 551-557.
    [12] 王晓锦. 三唑杀菌剂衍生物的合成及抗菌活性研究[D]. 新乡: 河南师范大学, 2013.

    WANG X J. Synthesis of coordination compounds, derivatives of triazole fungicide and investigation on their antimicrobial activity[D]. Xinxiang: Henan Normal University, 2013.
    [13] CAO X, LI F, HU M, et al. Chiral gamma-aryl-1H-1,2,4-triazole derivatives as highly potential antifungal agents: design, synthesis, structure, and in vitro fungicidal activities[J]. J Agric Food Chem, 2008, 56(23): 11367-11375. doi: 10.1021/jf8026843
    [14] KIMURA M, ETALE A. Antioxidative activities of novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter[J]. ChemInform, 2004, 35(50): 4287-4290.
    [15] SHAPIRO L A, OFFORD S J, ORDWAY G A. The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain[J]. Brain Res, 1995, 677(2): 250-256. doi: 10.1016/0006-8993(95)00155-J
    [16] 杨江婷, 张月成. 哌嗪及其衍生物的应用进展[J]. 精细化工中间体, 2018, 48(3): 6-9.

    YANG J T, ZHANG Y C. Progress in the application of piperazine and its derivatives[J]. Fine Chem Intermed, 2018, 48(3): 6-9.
    [17] 常颖, 胡羽鹏, 赵阳, 等. 哌嗪类新精神活性物质综述[J]. 刑事技术, 2016(4): 317-321.

    CHANG Y, HU Y P, ZHAO Y, et al. Review of new piperazine-type psychoactive substances[J]. Forensic Sci Technol, 2016(4): 317-321.
    [18] 刘长令, 杨吉春, 王军锋, 等. 含哌嗪的二卤丙烯醚类化合物与应用: CN101921228A[P]. 2010-12-22.

    LIU C L, YANG J C, WANG J F, et al. Piperazine-contained propylene ether dihalide compound and applications thereof: CN101921228A[P]. 2010-12-22.
    [19] 刘长令. 新农药创新方法与应用 (1)-中间体衍生化方法[J]. 农药, 2011, 50(1): 20-22. doi: 10.3969/j.issn.1006-0413.2011.01.005

    LIU C L. New approach for agrochemical discovery and application (1): intermediate derivatization method[J]. Agrochemicals, 2011, 50(1): 20-22. doi: 10.3969/j.issn.1006-0413.2011.01.005
    [20] 吴清来, 李永强, 杨新玲, 等. Aspernigerin类似物的合成及生物活性研究[J]. 有机化学, 2012, 32(4): 747-754. doi: 10.6023/cjoc1110091

    WU Q L, LI Y Q, YANG X L, et al. Synthesis and bioactivity of Aspernigerin analogues[J]. Chinese J Org Chem, 2012, 32(4): 747-754. doi: 10.6023/cjoc1110091
    [21] 张敏, 张立孔, 孟振国, 等. 1-[2-苄氧基-2-(2,4-二氟苯基) 乙基]-1H-1,2,4-三唑衍生物的合成及杀菌活性[J]. 农药学学报, 2020, 22(3): 413-422.

    ZHANG M, ZHANG L K, MENG Z G, et al. Synthesis and fungicidal activities of 1-[2-benzyloxy-2-(2,4-difluorophenyl) ethyl]-1H-1,2,4-triazole derivatives[J]. Chin J Pestic Sci, 2020, 22(3): 413-422.
    [22] 吴清来, 凌云. 哌嗪类衍生物在农药创制中的应用[J]. 农药, 2016, 55(11): 785-789, 810.

    WU Q L, LING Y. Applications of piperazine analogues in agrochemicals discovery[J]. Agrochemicals, 2016, 55(11): 785-789, 810.
    [23] CAI M Y, LI Z, FAN F, et al. Design and synthesis of novel insecticides based on the serotonergic ligand 1-[(4-aminophenyl) ethyl]-4-[3-(trifluoromethyl) phenyl]piperazine (papp)[J]. J Agric Food Chem, 2010, 58(5): 2624-2629. doi: 10.1021/jf902640u
    [24] 彭壮, 王明慧. 新型含氟吡啶哌嗪类衍生物的设计、合成与生物活性[J]. 农药, 2018, 57(9): 641-644.

    PENG Z, WANG M H. Design, synthesis and biological activity of novel fluoropyridine piperazine derivatives[J]. Agrochemicals, 2018, 57(9): 641-644.
    [25] 路小娟, 赵庆杰, 叶光明, 等. 1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(N-环丙基-N-取代氨基)-2-丙醇的合成及其抗真菌活性[J]. 第二军医大学学报, 2008, 29(11): 1380-1383. doi: 10.3321/j.issn:0258-879X.2008.11.025

    LU X J, ZHAO Q J, YE G M, et al. Synthesis of 1-(1H-1,2,4-triazole-1-y1)-2-(2,4-difluoro-pheny1)-3-(N-cyclopropyl-N-substituted amino)-2-propanols and its antifungal activity[J]. Acad J Second Mil Med Univ, 2008, 29(11): 1380-1383. doi: 10.3321/j.issn:0258-879X.2008.11.025
    [26] NELSON R, KESTERNICH V, PEREZ-FEHRMANN M, et al. Synthesis and antifungal activity of phenacyl azoles[J]. J Chem Res-S, 2014, 38(9): 549-552. doi: 10.3184/174751914X14107905836359
    [27] 韩生华, 孟双明, 温雪山, 等. N-取代苄基-N'-苯甲酰氧乙基哌嗪的合成[J]. 山西农业大学学报(自然科学版), 2010, 30(1): 77-80.

    HAN S H, MENG S M, WEN X S, et. al. Synthesis of 2-(4-substituted benzylpiperazin-1-yl) ethyl benzoate[J]. J Shanxi Agric Univ (Nat Sci Ed), 2010, 30(1): 77-80.
    [28] ZHANG C, TAN C, ZU X, et al. Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors[J]. Eur J Med Chem, 2011, 46(4): 1404-1414. doi: 10.1016/j.ejmech.2011.01.020
    [29] 农药室内生物测定实验准则 杀菌剂第2部分: 抑制病原真菌菌丝生长实验平皿法: NY/T1156.2—2006[S]. 北京: 中国农业大学出版社, 2006.

    Pesticides guidelines for laboratory bioactivity tests: Part 2: Petri plate test for determining fungicide inhibition of mycelial growth: NY/T1156.2—2006[S]. BeiJing: China Agriculture Press, 2006.
    [30] 张宗炳. 杀虫剂的毒力测定[M]. 北京: 科学技术出版社, 1985: 388-391.

    ZHANG Z B. Toxicity determination of insecticides[M]. Beijing: Science and Technology Press, 1985: 388-391.
    [31] 杨莹莹, 赖晓依, 赖多, 等. 6种农药对斜纹夜蛾和甜菜夜蛾的杀虫活性测定[J]. 湖南人文科技学院学报, 2017, 34(6): 107-113. doi: 10.3969/j.issn.1673-0712.2017.06.023

    YANG Y Y, LAI X Y, LAI D, et al. Determination of insecticidal activity of 6 pesticides against Spodoptera litura and Spodoptera exigua[J]. J Hunnan Univ Humanities Sci and Tech, 2017, 34(6): 107-113. doi: 10.3969/j.issn.1673-0712.2017.06.023
  • 新型三唑哌嗪类衍生物的合成及生物活性_目标化合物核磁谱图及数据.doc.docx
  • 加载中
图(1) / 表(3)
计量
  • 文章访问数:  881
  • HTML全文浏览量:  426
  • PDF下载量:  51
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-08-19
  • 录用日期:  2020-09-19
  • 刊出日期:  2021-04-10

目录

    /

    返回文章
    返回