Design, Synthesis and Bioactivity of Novel 2-Phenylethanol Ester Derivatives Containing Monoterpene Fragments

doi:10.6023/cjoc202407021

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (1): 196-204.DOI: 10.6023/cjoc202407021 Previous Articles Next Articles

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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

潘世香^a, 刘彦^a, 石卓^a, 路星星^a, 秦耀果^b, 渠成^c, 陈晨^a, 杨新玲^a^,^*()

a 中国农业大学理学院应用化学系北京 100193
b 中国农业大学植物保护学院昆虫学系北京 100193
c 北京市农林科学院植物保护研究所北京 100097

收稿日期:2024-07-09 修回日期:2024-08-16 发布日期:2024-09-29
作者简介:
†共同第一作者
基金资助:
国家自然科学基金(22277136)

Design, Synthesis and Bioactivity of Novel 2-Phenylethanol Ester Derivatives Containing Monoterpene Fragments

Shixiang Pan^a, Yan Liu^a, Zhuo Shi^a, Xingxing Lu^a, Yaoguo Qin^b, Cheng Qu^c, Chen Chen^a, Xinling Yang^a()

a Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193
b Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193)
c Institute of Plant Protection, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097

Received:2024-07-09 Revised:2024-08-16 Published:2024-09-29
Contact: *E-mail: yangxl@cau.edu.cn
About author:
†These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(22277136)

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Abstract

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

Cite this article

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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Fig. & Tab. 9

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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

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

Design, Synthesis and Bioactivity of Novel 2-Phenylethanol Ester Derivatives Containing Monoterpene Fragments

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References 24

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Compd.	Carcinogenicity^a	Honey bee toxicity^b	Oral rat^c
Compd.	Carcinogenicity^a	Honey bee toxicity^b	LD₅₀/(mg•kg^－1)	Toxicity grade (US EPA)^d
3a	None	Low	6391.10	Low
3b	None	Low	3538.74	Low
3c	None	Low	3453.83	Low
3d	None	Low	3568.16	Low
3e	None	Low	3480.17	Low
3f	None	Low	3665.71	Low
3g	None	Low	3342.51	Low
3h	None	Low	3177.02	Low
3i	None	Low	2500.96	Low
3j	None	Low	3171.57	Low
3k	None	Low	4847.61	Low
3l	None	Low	4524.47	Low
3m	None	Low	3032.48	Low
3n	None	Low	704.82	Low
3o	None	Low	1218.56	Low
3p	None	Low	1261.99	Low