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Thiasporine A类似物的设计、合成和抑菌活性

陈顺顺 朱祥 时锦超 王美美 胡慈银 廖灿 张勇 李俊凯

陈顺顺, 朱祥, 时锦超, 王美美, 胡慈银, 廖灿, 张勇, 李俊凯. Thiasporine A类似物的设计、合成和抑菌活性[J]. 农药学学报, 2022, 24(2): 280-288. doi: 10.16801/j.issn.1008-7303.2021.0172
引用本文: 陈顺顺, 朱祥, 时锦超, 王美美, 胡慈银, 廖灿, 张勇, 李俊凯. Thiasporine A类似物的设计、合成和抑菌活性[J]. 农药学学报, 2022, 24(2): 280-288. doi: 10.16801/j.issn.1008-7303.2021.0172
CHEN Shunshun, ZHU Xiang, SHI Jinchao, WANG Meimei, HU Ciyin, LIAO Can, ZHANG Yong, LI Junkai. Design, synthesis and fungicidal activities of Thiasporine A analogues[J]. Chinese Journal of Pesticide Science, 2022, 24(2): 280-288. doi: 10.16801/j.issn.1008-7303.2021.0172
Citation: CHEN Shunshun, ZHU Xiang, SHI Jinchao, WANG Meimei, HU Ciyin, LIAO Can, ZHANG Yong, LI Junkai. Design, synthesis and fungicidal activities of Thiasporine A analogues[J]. Chinese Journal of Pesticide Science, 2022, 24(2): 280-288. doi: 10.16801/j.issn.1008-7303.2021.0172

Thiasporine A类似物的设计、合成和抑菌活性

doi: 10.16801/j.issn.1008-7303.2021.0172
基金项目: 国家重点研发计划 (2018YFD0200500);国家自然科学基金 (31672069)
详细信息
    作者简介:

    陈顺顺,18736927359@163.com

    通讯作者:

    李俊凯,junkaili@sina.com.

  • 中图分类号: O626.2;TQ450.11

Design, synthesis and fungicidal activities of Thiasporine A analogues

Funds: the National Key R&D Program of China (2018YFD0200500), the National Natural Science Foundation of China (31672069)
  • 摘要: Thiasporine A是从海洋放线菌Actinomycetospora chlora SNC-032代谢物中分离得到一个含有苯基噻唑环结构的天然产物,对肺癌细胞系H2122具有中等毒性。本文以取代苯甲腈为原料合成了Thiasporine A ( 4o ) 和29个Thiasporine A类似物( 3a ~ 3o4a ~ 4n ),其中24个未见文献报道, 利用 核磁共振氢谱、碳谱和高分辨质谱对化合物的结构进行了表征,并测定了Thiasporine A及其类似物的抑菌活性。结果表明,在200 μmol/L的浓度下,大部分目标化合物对5种供试植物病原真菌均有一定的抑制效果。其中:化合物 3e3i 对水稻纹枯病菌Rhizoctonia solani的抑制率分别为84.5%和84.4%,其EC50值分别为17.3 μmol/L和21.9 μmol/L;化合物 4b4j 对白芨白绢病菌Selerotium rolfsii的抑制率为100%;化合物 4b 对烟草黑胫病菌Phytophthora parasitica抑制率为83.3%,高于商品药剂噻呋酰胺;化合物 3g 对5种供试病原菌的抑制率都在70%以上。
  • 1  Thiasporine A (I)及其类似物 (II)

    1.  Thiasporine A (I) and Thiasporine A analogue (II)

    2  目标化合物3a~3o和4a~4o的合成路线

    2.  Synthetic route of the target compounds 3a-3o and 4a-4o

    表  1  目标化合物3a~3o和4a~4o对5种植物病原菌的抑菌活性(抑制率/%)

    Table  1.   Fungicidal activities (inhibition rate/%) of target compounds 3a-3o and 4a-4o against five fungi

    化合物
    Compd.
    取代基
    R
    浓度
    Concentration/
    (μmol/L)
    水稻纹枯病菌
    R. solani
    油菜菌核病菌
    S. sclerotiorum
    油菜黑胫病菌
    L. biglobosa
    白芨白绢病菌
    S. rolfsii
    烟草黑胫病菌
    P. parasitica
    3a H 200 72.6±0.1 31.4±0.4 47.5±0.1 60.5±0.0 49.2±0.1
    100 62.8±0.0 13.3±0.1 9.70±0.2 32.9±0.3 16.2±0.0
    3b 2-CH3 200 70.6±0.1 26.2±0.4 39.0±0.1 84.1±0.1 48.5±0.0
    100 59.4±0.0 14.6±0.1 18.3±0.1 63.0±0.1 0
    3c 2-OCH3 200 62.0±0.0 53.7±0.4 38.9±0.1 65.6±0.1 37.4±0.1
    100 41.1±0.1 30.2±0.1 32.6±0.1 28.7±0.4 0
    3d 2-CF3 200 73.9±0.0 31.3±0.4 26.9±0.0 94.7±0.0 34.2±0.1
    100 55.7±0.1 23.0±0.0 21.8±0.1 82.3±0.1 10.9±0.1
    3e 2-OCF3 200 84.5±0.0 57.5±0.2 54.2±0.0 87.9±0.1 63.6±0.1
    100 70.0±0.0 34.2±0.1 35.3±0.1 65.7±0.2 25.3±0.2
    3f 2-OH 200 50.4±0.1 35.3±0.4 43.1±0.1 20.8±0.1 20.7±0.1
    100 55.5±0.1 29.1±0.0 35.2±0.1 20.1±0.3 28.2±0.1
    3g 2-F 200 77.3±0.0 81.8±0.2 80.6±0.0 92.9±0.0 70.6±0.0
    100 64.7±0.0 56.1±0.1 46.3±0.1 48.0±0.2 59.1±0.1
    3h 2-Cl 200 78.0±0.0 55.9±0.3 55.1±0.1 82.0±0.0 54.7±0.1
    100 63.1±0.0 41.1±0.1 35.2±0.1 69.3±0.1 19.1±0.1
    3i 2-Br 200 84.4±0.0 63.8±0.3 62.3±0.0 92.6±0.1 50.8±0.1
    100 68.8±0.0 34.1±0.1 33.4±0.2 76.2±0.1 29.8±0.0
    3j 4-CF3 200 63.8±0.0 22.7±0.4 53.2±0.0 50.6±0.0 46.7±0.0
    100 50.1±0.0 10.5±0.1 8.10±0.2 25.7±0.3 17.2±0.1
    3k 4-OH 200 52.3±0.0 22.4±0.5 49.1±0.0 10.2±0.1 35.5±0.0
    100 32.2±0.1 16.7±0.1 19.5±0.2 14.3±0.3 0.50±0.1
    3l 4-Cl 200 60.3±0.1 19.7±0.4 45.0±0.0 40.2±0.0 23.0±0.1
    100 55.4±0.1 19.5±0.1 18.3±0.2 36.2±0.2 21.9±0.1
    3m 4-NH2 200 44.6±0.0 13.3±0.6 16.1±0.1 8.70±0.1 34.4±0.0
    100 26.8±0.0 2.30±0.1 8.30±0.2 12.2±0.3 0
    3n 3-NH2 200 53.9±0.1 15.1±0.5 5.30±0.0 10.7±0.0 15.7±0.1
    100 29.9±0.0 8.30±0.2 10.1±0.1 13.1±0.4 0
    3o 2-NH2 200 45.5±0.1 19.9±0.4 16.9±0.1 29.6±0.1 5.9±0.1
    100 47.2±0.0 9.60±0.1 12.9±0.2 22.2±0.3 0
    4a H 200 43.8±0.0 21.5±0.0 12.2±0.1 84.6±0.1 71.3±0.1
    100 38.4±0.1 21.1±0.0 9.00±0.0 41.5±0.3 70.2±0.1
    4b 2-CH3 200 26.2±0.0 25.7±0.1 23.0±0.0 100.0±0.0 83.3±0.0
    100 32.2±0.1 21.6±0.1 13.3±0.0 40.9±0.3 71.8±0.0
    4c 2-OCH3 200 34.7±0.1 36.9±0.0 23.9±0.0 97.9±0.0 77.7±0.0
    100 28.0±0.0 28.4±0.1 17.4±0.1 44.1±0.3 54.8±0.3
    4d 2-CF3 200 14.1±0.0 14.2±0.0 12.3±0.1 58.3±0.1 35.2±0.2
    100 26.7±0.0 14.1±0.1 6.40±0.1 26.0±0.3 27.1±0.0
    4e 2-OCF3 200 54.2±0.0 43.5±0.1 38.6±0.0 75.2±0.0 74.6±0.1
    100 35.1±0.1 29.2±0.1 28.3±0.1 66.8±0.2 61.7±0.1
    4f 2-OH 200 22.8±0.0 21.7±0.0 16.3±0.0 83.0±0.0 58.1±0.3
    100 29.0±0.0 24.1±0.1 14.3±0.1 50.3±0.4 54.6±0.0
    4g 2-F 200 37.6±0.1 28.0±0.1 15.3±0.1 59.9±0.1 67.1±0.1
    100 25.2±0.1 21.3±0.1 10.0±0.1 40.2±0.3 62.1±0.0
    4h 2-Cl 200 44.1±0.0 29.7±0.0 21.0±0.1 73.4±0.1 69.1±0.1
    100 38.2±0.1 24.2±0.2 15.7±0.1 61.5±0.2 64.1±0.1
    4i 2-Br 200 42.0±0.0 22.4±0.0 15.3±0.0 78.3±0.0 69.3±0.0
    100 30.9±0.0 21.5±0.1 7.90±0.1 60.1±0.3 52.9±0.0
    4j 4-CF3 200 37.1±0.0 37.2±0.0 46.8±0.0 100.0±0.0 74.4±0.0
    100 33.6±0.1 25.9±0.2 20.4±0.1 69.4±0.1 63.1±0.0
    4k 4-OH 200 10.0±0.1 8.90±0.0 5.30±0.1 0 0
    100 28.8±0.1 20.9±0.1 4.80±0.1 1.20±0.5 2.70±0.1
    4l 4-Cl 200 38.0±0.1 32.8±0.0 28.6±0.0 71.4±0.0 75.3±0.1
    100 34.2±0.0 36.6±0.0 30.4±0.1 90.6±0.1 75.7±0.0
    4m 4-NH2 200 15.6±0.1 8.70±0.0 4.40±0.1 0 6.10±0.1
    100 31.2±0.0 19.2±0.1 14.3±0.0 0 4.70±0.1
    4n 3-NH2 200 47.5±0.1 21.9±0.0 24.7±0.1 4.90±0.0 0
    100 54.0±0.1 22.5±0.1 13.7±0.0 11.3±0.5 2.20±0.1
    thiasporine A(4o) 2-NH2 200 41.0±0.1 22.3±0.1 15.4±0.1 42.1±0.0 40.1±0.0
    100 44.1±0.1 16.5±0.0 10.2±0.1 21.1±0.4 13.2±0.1
    噻呋酰胺 thifluzamide 200 95.8±0.1 82.4±0.1 80.9±0.1 100.0±0.0 4.20±0.3
    100 94.3±0.0 78.9±0.1 77.6±0.1 100.0±0.0 2.80±0.1
    注:每个处理重复3次(平均值±标准差)。Note: Values are the mean ± SD of three replicates.
    下载: 导出CSV

    表  2  部分化合物对水稻纹枯病菌、白芨白绢病菌和烟草黑胫病菌的EC50

    Table  2.   EC50 of some compounds against R. solani, S. rolfsii and P. parasitica

    植物病原菌
    Fungi
    化合物
    Compd.
    取代基
    R
    回归方程
    Regression equation
    相关系数(r)
    Correlation cofficient
    EC50/(μmol/L)
    水稻纹枯病菌
    R. solani
    3b 2-CH3 y = 1.0099x + 6.4407 0.9597 37.4±0.2
    3d 2-CF3 y = 0.6739x + 5.9595 0.9802 37.7±1.8
    3e 2-OCF3 y = 0.8071x + 6.4211 0.9753 17.3±0.7
    3h 2-Cl y = 0.7788x + 6.3693 0.9901 17.4±0.6
    3i 2-Br y = 0.9425x + 6.5643 0.9893 21.9±0.4
    thiasporine A (4o) 2-NH2 y = 0.7138x + 5.6253 0.9908 133.1±2.2
    噻呋酰胺 (thifluzamide) y = 0.4128x + 6.5125 0.9943 0.2±0.0
    白芨白绢病菌
    S. rolfsii
    3b 2-CH3 y = 1.3917x + 6.8031 0.9892 50.6±2.2
    3d 2-CF3 y = 1.8682x + 7.6471 0.9869 38.3±0.2
    3e 2-OCF3 y = 1.3353x + 7.0206 0.9983 30.7±2.1
    3h 2-Cl y = 1.4759x + 7.2071 0.9927 32.2±1.4
    3i 2-Br y = 1.4856x + 7.3205 0.9828 27.4±0.6
    4e 2-OCF3 y = 2.3065x + 7.9269 0.8979 53.8±1.7
    4h 2-Cl y = 2.6702x + 8.5410 0.9210 47.2±1.3
    4i 2-Br y = 2.3683x + 8.2745 0.9466 41.4±2.7
    4j 4-CF3 y = 2.1622x + 7.9613 0.9477 42.7±2.6
    4l 4-Cl y = 2.5116x + 8.5765 0.9469 37.7±1.2
    thiasporine A (4o) 2-NH2 y = 0.7253x + 5.1327 0.9630 656.1±0.9
    噻呋酰胺 (thifluzamide) y = 0.8354x + 8.3636 0.9696 0.1±0.0
    烟草黑胫病菌
    P. parasitica
    4e 2-OCF3 y = 1.0434x + 6.4496 0.9973 40.8±1.4
    4h 2-Cl y = 1.1960x + 6.6059 0.9978 45.4±0.5
    4i 2-Br y = 1.5473x + 6.5358 0.9881 101.7±2.9
    4j 4-CF3 y = 1.4117x + 6.7695 0.9246 55.8±0.5
    4l 4-Cl y = 1.3102x + 7.1177 0.9773 24.2±0.4
    thiasporine A(4o) 2-NH2 y = 1.5932x + 5.9353 0.9952 258.8±1.9
    噻呋酰胺(thifluzamide) y = 1.6643x + 6.3319 0.9948 158.4±1.6
    注:每个处理重复3次(平均值±标准差)。Note: Values are the mean ± SD of three replicates.
    下载: 导出CSV
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  • ThiasporineA类似物的设计、合成和抑菌活性_目标化合物的结构鉴定图谱(SupportingInformation).pdf
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出版历程
  • 收稿日期:  2021-09-29
  • 录用日期:  2021-11-03
  • 网络出版日期:  2021-11-08
  • 刊出日期:  2022-04-10

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