新型含单萜片段的苯乙醇酯类衍生物的设计、合成及生物活性研究

doi:10.6023/cjoc202407021

摘要/Abstract

为了发现新型蚜虫控制剂, 以植物挥发物苯乙醇为先导, 采用活性亚结构拼接的方法设计合成了16个含单萜片段的苯乙醇酯类衍生物. 通过荧光竞争结合的方法测定了化合物对豌豆蚜(Acyrthosiphon pisum)和异色瓢虫(Harmonia axyridis)气味结合蛋白(odorant binding protein, OBP)的结合活性. 所有化合物对两种蛋白均具有良好的结合活性且优于先导苯乙醇. 行为实验结果表明所有目标化合物对豌豆蚜具有驱避活性(35.9%~57.7%), 其中3-甲氧基苯乙基(E)-3,7-二甲基辛-2,6-二烯酸酯(3f)的驱避活性最佳; 此外, 化合物3f还对异色瓢虫具有显著的吸引活性. 通过分子对接研究了3f与两种OBP蛋白的结合模式, 发现引入单萜片段后显著增强了化合物与蛋白之间的疏水相互作用. 初步毒性测试表明, 化合物3f对异色瓢虫安全, 在蚜虫的绿色防控中展现出良好的应用前景.

关键词: 苯乙醇, 气味结合蛋白, 驱避蚜虫, 吸引瓢虫, 生态友好

To discover novel aphid control agents, taking plant volatile 2-phenylethanol as a lead, 16 ester derivatives of 2-phenylethanol containing monoterpenoid fragments were designed and synthesized by the method of active substructure splicing. The binding affinity of target compounds to odorant binding proteins (OBP) of Acyrthosiphon pisum and Harmonia axyridis was measured via fluorescent competitive binding assay. All compounds showed good binding affinity to both proteins, better than 2-phenylethanol. Behavioral experiments showed that all target compounds had repelling activity against A. pisum (35.9%~57.7%) with 3-methoxyphenethyl (E)-3,7-dimethylocta-2,6-dienoate (3f) exhibiting the best repellency. In addition, 3f also showed significant attractive activity to H. axyridis. The binding mode of 3f with the OBP protein was investigated by molecular docking, revealing that the introduction of the monoterpenoid fragment significantly enhanced the hydrophobic interactions between compounds and proteins. Preliminary toxicity tests indicated that 3f was safe to H. axyridis, showing great application prospects in the green control of aphids.

Key words: 2-phenylethanol, odorant binding protein, repel aphid, attract ladybug, eco-friendliness

引用此文

潘世香, 刘彦, 石卓, 路星星, 秦耀果, 渠成, 陈晨, 杨新玲. 新型含单萜片段的苯乙醇酯类衍生物的设计、合成及生物活性研究[J]. 有机化学, 2025, 45(1): 196-204.

Shixiang Pan, Yan Liu, Zhuo Shi, Xingxing Lu, Yaoguo Qin, Cheng Qu, Chen Chen, Xinling Yang. Design, Synthesis and Bioactivity of Novel 2-Phenylethanol Ester Derivatives Containing Monoterpene Fragments[J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 196-204.

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Compd.	R	ApisOBP9	HaxyOBP15
3a	H	0.53±0.01	0.36±0.03
3b	2-CH₃	0.47±0.002	0.48±0.01
3c	3-CH₃	0.34±0.03	0.42±0.08
3d	4-CH₃	0.47±0.03	0.54±0.17
3e	2-OCH₃	0.94±0.16	0.45±0.03
3f	3-OCH₃	0.49±0.06	1.15±0.37
3g	4-OCH₃	1.47±0.41	0.47±0.04
3h	2-Cl	0.50±0.049	0.41±0.03
3i	3-Cl	0.50±0.051	0.43±0.01
3j	4-Cl	0.46±0.01	0.39±0.05
3k	2-F	0.47±0.12	0.41±0.02
3l	3-F	0.39±0.03	0.43±0.06
3m	4-F	0.30±0.04	0.33±0.02
3n	2-Br	0.59±0.01	0.82±0.15
3o	3-Br	0.49±0.004	0.50±0.03
3p	4-Br	0.64±0.11	0.64±0.01
2-Phenylethanol		0.10±0.01	0.08±0.01

Compd.	R	ApisOBP9	HaxyOBP15
3a	H	0.53±0.01	0.36±0.03
3b	2-CH₃	0.47±0.002	0.48±0.01
3c	3-CH₃	0.34±0.03	0.42±0.08
3d	4-CH₃	0.47±0.03	0.54±0.17
3e	2-OCH₃	0.94±0.16	0.45±0.03
3f	3-OCH₃	0.49±0.06	1.15±0.37
3g	4-OCH₃	1.47±0.41	0.47±0.04
3h	2-Cl	0.50±0.049	0.41±0.03
3i	3-Cl	0.50±0.051	0.43±0.01
3j	4-Cl	0.46±0.01	0.39±0.05
3k	2-F	0.47±0.12	0.41±0.02
3l	3-F	0.39±0.03	0.43±0.06
3m	4-F	0.30±0.04	0.33±0.02
3n	2-Br	0.59±0.01	0.82±0.15
3o	3-Br	0.49±0.004	0.50±0.03
3p	4-Br	0.64±0.11	0.64±0.01
2-Phenylethanol		0.10±0.01	0.08±0.01

Compd.	R	Repellency rate^a/%
3a	H	40.7±5.4
3b	2-CH₃	38.8±6.8
3c	3-CH₃	34.4±7.4
3d	4-CH₃	45.7±7.5
3e	2-OCH₃	50.9±2.8
3f	3-OCH₃	57.7±2.5
3g	4-OCH₃	53.5±4.1
3h	2-Cl	46.2±2.7
3i	3-Cl	43.8±6.0
3j	4-Cl	44.9±3.3
3k	2-F	42.9±3.3
3l	3-F	35.9±2.6
3m	4-F	41.0±5.4
3n	2-Br	45.3±4.9
3o	3-Br	48.3±4.1
3p	4-Br	45.7±5.9
2-Phenylethanol		37.2±2.5

Compd.	R	Repellency rate^a/%
3a	H	40.7±5.4
3b	2-CH₃	38.8±6.8
3c	3-CH₃	34.4±7.4
3d	4-CH₃	45.7±7.5
3e	2-OCH₃	50.9±2.8
3f	3-OCH₃	57.7±2.5
3g	4-OCH₃	53.5±4.1
3h	2-Cl	46.2±2.7
3i	3-Cl	43.8±6.0
3j	4-Cl	44.9±3.3
3k	2-F	42.9±3.3
3l	3-F	35.9±2.6
3m	4-F	41.0±5.4
3n	2-Br	45.3±4.9
3o	3-Br	48.3±4.1
3p	4-Br	45.7±5.9
2-Phenylethanol		37.2±2.5

Compd.	Male				Female
Compd.	Choice/%	Chi-squre	p-value	Significance	Choice/%	Chi-squre	p-value	Significance
3f	71.7	10.42	0.0012	**	68.3	7.36	0.0067	**
2-Phenylethanol	70.0	8.82	0.003	*	60.0	2.02	0.1552	ns