天然杀线虫先导化合物Waltherione A类似物的合成及杀线虫活性

张羲; 谢世爽; 胡展; 张北京; 刘启凤; 丁晓帆; 谢佳; 邵雨; 孙然锋

doi:10.16801/j.issn.1008-7303.2021.0150

天然杀线虫先导化合物Waltherione A类似物的合成及杀线虫活性

doi: 10.16801/j.issn.1008-7303.2021.0150

张羲^{1, 2,},
谢世爽^{1, 2},
胡展^{1, 2},
张北京^{1, 2},
刘启凤^{1, 2},
丁晓帆^{1, 2},
谢佳^{1, 2},
邵雨³,
孙然锋^{1, 2, ,}

1.
热带农林生物灾害绿色防控教育部重点实验室，海南大学，海口 570228
2.
海南大学植物保护学院，海口 570228
3.
海南省烟草公司儋州公司，海南儋州 571700

基金项目: 国家自然科学基金 (22067004)；海南省自然科学基金资助(321CXTD436, 321QN177, 321QN178)；海南大学高层次人才引进启动经费 (kyqd1640)；海南省烟草公司科技计划(2018003).

详细信息

作者简介:
张羲，20090403210004@hainanu.edu.cn

通讯作者:
孙然锋，srf18@hainanu.edu.cn.

中图分类号: S482.51；TQ450
计量
- 文章访问数: 285
- HTML全文浏览量: 39
- PDF下载量: 71
- 被引次数: 0
出版历程
- 收稿日期: 2021-06-21
- 录用日期: 2021-09-17
- 网络出版日期: 2021-10-19
- 刊出日期: 2022-04-01

Synthesis and nematicidal activity of natural nematicidal lead compound Waltherione A analogues

ZHANG Xi^{1, 2
,},
XIE Shishuang^{1, 2},
HU Zhan^{1, 2},
ZHANG Beijing^{1, 2},
LIU Qifeng^{1, 2},
DING Xiaofan^{1, 2},
XIE Jia^{1, 2},
SHAO Yu³,
SUN Ranfeng^{1, 2
, ,}

1.
Key Laboratory of Green Prevention and Control of Tropical Agriculture and Forestry Biological Disasters Ministry of Education, Hainan University, Haikou 570228, China
2.
College of Plant Protection, Hainan University, Haikou 570228, China
3.
Danzhou Tobacco Company, Hainan Provincial Branch of CNTC, Danzhou 571700, Hainan Province, China

Funds: the National Natural Science Foundation of China (22067004), Hainan Provincial Natural Science Foundation of China (321CXTD436, 321QN177, 321QN178), Startup Foundation for Introduced Talents of Hainan University (kyqd1640), Annual Science and Technology Project of Hainan Provincial Tobacco Company of CNTC (2018003).

摘要

摘要: 为了找出天然杀线虫先导生物碱Waltherione A的关键药效基团并简化其结构，以2,3-二甲氧基苯甲醛和3,4-二甲氧基苯甲醛为原料，经过分子内傅克烷基化反应形成苯并七元氧桥环，并用不同的取代基与桥环相连，合成了12个Waltherione A类似物，其中8个化合物未见文献报道，所有目标化合物的结构均通过核磁共振氢谱(¹H NMR)、碳谱(¹³C NMR)及高分辨质谱(HRMS)确证。采用浸虫法测定了目标化合物对南方根结线虫Meloidogyne incognita的杀虫活性。结果表明：目标化合物杀线虫的活性均低于Waltherione A，其中化合物 A-12 在200 μg/mL下对南方根结线虫2龄幼虫72 h的致死率为69.7%。 A-12 的杀线虫活性高于其他目标化合物，表明芳香取代基与苯并七元氧桥环相连时对化合物活性的提升存在积极作用，这为进一步的结构优化提供了方向。
- 生物碱 /
- Waltherione A /
- 结构优化 /
- 南方根结线虫 /
- 杀线虫活性 /
- 构效关系
Abstract: To find out the key pharmacores of Waltherione A which is a natural nematicidal lead alkaloid and simplify its structure, twelve Waltherione A analogues were synthesized from 2,3-dimethoxybenzaldehyde and 3,4-dimethoxybenzaldehyde through intramolecular Friedel-Crafts alkylation reaction, and connected with the bridge ring with different substituents. Among them, eight compounds have not been reported in the literature. The structures of all target compounds were confirmed by ¹H NMR,¹³C NMR and HRMS. The nematicidal activity of the target compounds against Meloidogyne incognita was determined by the immersion method. The results showed that the nematicidal activity of all the target compounds was lower than that of Waltherione A. The 72-h mortality of compound A-12 against the 2^nd instar larvae of M. incognita was 69.7% at 200 μg/mL, and the nematicidal activity of compound A-12 was higher in comparation with other compounds. The results showed that the aromatic substituents connected with bridge ring had a positive effect on the activity of the compound, which provides a direction for further structural optimization.
- alkaloids /
- Waltherione A /
- structural optimization /
- Meloidogyne incongnita /
- nematicidal activity /
- structure activity relationship

HTML全文

1 Waltherione A的结构和设计思路

1. Structure of Waltherione A and the design strategy

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2 目标化合物的合成路线

2. Synthetic routes of target compounds

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3 合成目标化合物A-5的反应机理

3. Reaction mechanism of synthesis of target compound A-5

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表 1 化合物A-7~A-13和B-7中R¹、R²的结构

Table 1. The structures of R¹ and R² in compounds A-7-A-13 and B-7

化合物 Compound	R¹	R²
A-7	3,4-(OCH₃)₂
B-7	2,3-(OCH₃)₂
A-8	3,4-(OCH₃)₂
A-9	3,4-(OCH₃)₂
A-10	3,4-(OCH₃)₂
A-11	3,4-(OCH₃)₂
A-12	3,4-(OCH₃)₂
A-13	3,4-(OCH₃)₂

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表 2 目标化合物对南方根结线虫的致死活性 (校正死亡率/%)

Table 2. Nematicidal activity of the target compounds against Meloidogyne incongnita (Adjusted mortality/%)

化合物 Compound	200 μg/mL			100 μg/mL			50 μg/mL
化合物 Compound	24 h	48 h	72 h	24 h	48 h	72 h	24 h	48 h	72 h
A-5	9.9±0.7	13.8±1.4	14.9±1.1	2.3±0.1	4.3±0.2	4.9±0.6	—	—	—
A-6	8.3±0.2	12.3±1.5	13.2±0.8	3.4±0.8	4.5±1.1	5.7±0.8	—	—	—
A-7	12.3±0.4	19.6±0.2	25.3±0.1	5.7±0.3	7.8±0.1	9.3±0.7	—	—	—
A-8	12.5±0.1	22.6±0.4	28.3±0.2	3.1±0.2	5.8±0.1	9.9±0.8	—	—	—
A-9	11.7±0.1	18.9±0.6	26.8±0.5	5.2±0.5	6.4±0.1	8.8±0.4	—	—	—
A-10	11.6±0.2	16.8±0.5	27.1±0.1	2.2±0.6	4.3±0.1	7.8±0.1	—	—	—
A-11	6.4±0.1	14.2±0.4	19.0±0.2	1.8±0.6	3.6±0.1	6.7±0.6	—	—	—
A-12	47.8±0.3	64.1±0.5	69.7±1.3	9.0±0.2	17.2±0.1	27.3±0.2	2.2±0.2	11.9±0.5	16.8±0.7
A-13	9.9±0.2	12.4±0.9	20.0±0.7	2.0±0.9	4.3±0.1	7.0±0.3	—	—	—
B-5	7.6±0.2	14.7±0.1	15.5±0.1	3.5±0.8	4.7±0.1	5.2±0.6	—	—	—
B-6	8.1±0.1	13.1±0.3	14.6±0.1	2.4±0.6	3.8±0.1	4.4±0.7	—	—	—
B-7	10.5±0.6	20.6±0.2	26.3±1.3	4.7±0.1	6.1±0.1	9.4±0.9	—	—	—
Waltherione A	—	—	—	—	—	—	97.1±1.7	100.0±0.0	100.0±0.0
阿维菌素 abamectin	—	—	—	—	—	—	100.0±0.0	100.0±0.0	100.0±0.0
注：“—” 未测试。Note: ' — ' not tested.

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