顺/反-1,2,4-噁二唑衍生物的结构确证

doi:10.11938/cjmr20253184

波谱学杂志 ›› 2026, Vol. 43 ›› Issue (2): 164-174.doi: 10.11938/cjmr20253184cstr: 32225.14.cjmr20253184

顺/反-1,2,4-噁二唑衍生物的结构确证

高源¹^,^#, 刘心月¹^,^#, 王思宏²^,^*(), 胡伟³^,^§()

¹ 长白山天然药物研究教育部重点实验室，延边大学，吉林延吉 133002
² 延边大学分析测试中心，吉林延吉 133002
³ 松山湖材料实验室, 广东东莞 523008

收稿日期:2025-10-20 出版日期:2026-06-05 在线发表日期:2026-01-27
通讯作者: 王思宏,胡伟 E-mail:shwang@ybu.edu.cn;276193238@qq.com
作者简介:第一联系人：
^#共同第一作者
基金资助:
国家自然科学基金资助项目(22567024)

Structure Elucidation of cis- and trans-1,2,4-Oxadiazol Derivatives

GAO Yuan¹^,^#, LIU Xinyue¹^,^#, WANG Sihong²^,^*(), HU Wei³^,^§()

¹ Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China
² 21. Analysis and Inspection Center, Yanbian University, Yanji 133002, China
³ Songshan Lake Materials Laboratory, Dongguan 523008, China

Received:2025-10-20 Published:2026-06-05 Online:2026-01-27
Contact: WANG Sihong, HU Wei E-mail:shwang@ybu.edu.cn;276193238@qq.com

1. 附件材料.pdf(794KB)

摘要/Abstract

摘要：

顺反异构体的几何构型差异可导致其生物活性显著不同，对异构体进行分离与构型鉴定是评估其药效的关键．本研究合成了一对顺/反-1,2,4-噁二唑衍生物异构体即顺/反-4-[2-(3-((1H-吲哚-3-基)甲基)-1,2,4-噁二唑-5-基)乙烯基]-N,N-二甲基苯胺，并综合利用核磁共振（NMR）、傅里叶变换红外光谱（FT-IR）、高分辨质谱（HRMS）及理论计算，成功实现了这一对异构体的明确指认与区分．抗弓形虫活性评价表明，顺式异构体（化合物2，选择性指数SI = 1.50）的活性优于其反式异构体（化合物1，SI = 0.92）及阳性对照药螺旋霉素（SI = 0.98），充分体现了构型分离与鉴定在药物研究中的价值．本研究深化了对构型-活性关系的理解，为高选择性抗弓形虫药物的开发提供了新思路．

关键词: 1,2,4-噁二唑, 抗寄生虫药, 结构解析, 顺式构型, 核磁共振

Abstract:

The geometric configuration of cis-trans isomers critically influences their biological activities, making the separation and configurational identification essential for efficacy evaluation. In this study, cis/trans-1,2,4-oxadiazole derivatives were synthesized and comprehensively characterized by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), high-resolution mass spectrometry (HRMS), and theoretical calculations. This approach enabled unambiguous identification and distinction of a pair of isomers, including cis-4-[2-(3-((1H-indol-3-yl)methyl)-1,2,4-oxadiazol-5-yl)vinyl]-N,N-dimethylaniline and its trans-configuration analogue. Anti-Toxoplasma gondii activity assessment revealed that the cis-isomer (compound 2, selectivity index SI = 1.50) exhibited higher activity than the trans-isomer (compound 1, SI = 0.92) and the positive control spiramycin (SI = 0.98), highlighting the value of configurational separation and identification in pharmaceutical research. This study deepens the understanding of configuration-activity relationships and provides new insights for developing highly selective anti-Toxoplasma agents.

Key words: 1,2,4-oxadiazole, antiparasitic agents, structural elucidation, cis-configuration, NMR

中图分类号:

O482.53

高源, 刘心月, 王思宏, 胡伟. 顺/反-1,2,4-噁二唑衍生物的结构确证[J]. 波谱学杂志, 2026, 43(2): 164-174.

GAO Yuan, LIU Xinyue, WANG Sihong, HU Wei. Structure Elucidation of cis- and trans-1,2,4-Oxadiazol Derivatives[J]. Chinese Journal of Magnetic Resonance, 2026, 43(2): 164-174.

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参考文献 19

[1]	NEVESELY T, WIENHOLD M, MOLLOY J J, et al. Advances in the E→Z isomerization of alkenes using small molecule photocatalysts[J]. Chem Rev, 2022, 122(2): 2650-2694. doi: 10.1021/acs.chemrev.1c00324
[2]	CHU W, ZHOU D, GABA V, et al. Design, synthesis, and characterization of 3-(benzylidene)indolin-2-one derivatives as ligands for α-synuclein fibrils[J]. J Med Chem, 2015, 58(15): 6002-6017. doi: 10.1021/acs.jmedchem.5b00571 pmid: 26177091
[3]	GANGADASU B, REDDY M J R, RAVINDER M, et al. Synthesis, photochemical E (trans)→Z (cis) isomerization and antimicrobial activity of 2-chloro-5-methylpyridine-3-olefin derivatives[J]. Eur J Med Chem, 2009, 44(11): 4661-4667. doi: 10.1016/j.ejmech.2009.07.002
[4]	WANG S H, YIN X M. Assignments of nuclear magnetic resonance peak of 1-(2,6-diflurophenymethyl)-N-methyl-1H-1,2,3-triazole- 4-carboxamide[J]. Chin J Anal Chem, 2006, 34(3): 362-364.
	王思宏, 尹秀梅. 1-(2,6-二氟苯甲基)-N-甲基-1H-1,2,3-三唑-4-甲酰胺核磁共振峰的归属[J]. 分析化学, 2006, 34(3): 362-364.
[5]	WANG S H, KAN Y H. Experimental and theoretical studies of the absolute configuration of (2S,1′R) and (2R,1′R)-2-acetoxymethyl-3-phenyl-N-(1′-phenylethyl)-propionamide[J]. J Mol Struct, 2010, 981(1): 159-162. doi: 10.1016/j.molstruc.2010.07.049
[6]	SILVERSTEIN R M, WEBSTER F X, KIEMLE D J, et al. Spectrometric identification of organic compounds, 8th edition[M]. New York: John Wiley and Sons, 2014.
[7]	FAN Z, DUAN W, LIN G, et al. Synthesis and biological activities of novel (z)-/(e)-anisaldehyde-based oxime ester compounds[J]. Chem Biodivers, 2021, 18(7): e2100235. doi: 10.1002/cbdv.v18.7
[8]	TSUKAMOTO T, NAKATANI S, YOSHIOKA Y, et al. Comparison of larvicidal, adulticidal and acaricidal activity of two geometrical butylidenephthalide isomers[J]. Biol Pharm Bull, 2006, 29(3): 592-594. pmid: 16508176
[9]	GUANTAI E M, NCOKAZI K, EGAN T J, et al. Enone- and chalcone-chloroquinoline hybrid analogues: In silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies[J]. J Med Chem, 2011, 54(10): 3637-3649. doi: 10.1021/jm200149e
[10]	HORTY L G, DAEUBLE J F, CASTETTER S, et al. Synthesis, stability and insecticidal activity of 2-arylstilbenes[J]. Pest Manage Sci, 2019, 75(11): 3015-3023. doi: 10.1002/ps.v75.11
[11]	KAUSHIK A, MAKARANI N, BHARADAVA K, et al. Antiprotozoal agents-integration of drug discovery, medicinal chemistry, and advanced computational approaches: An in-depth review[J]. The Microbe, 2025, 7: 100395. doi: 10.1016/j.microb.2025.100395
[12]	WANG S H, ZHANG J D, YIN X M, et al. NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine[J]. Chinese J Magn Reson, 2020, 37(3): 390-398.
	王思宏, 张敬东, 尹秀梅, 等.6-(4-氯苯氧基)四唑并[5,1-a]酞嗪的核磁共振谱峰归属[J]. 波谱学杂志, 2020, 37(3): 390-398. doi: 10.11938/cjmr20192776
[13]	JIN Y J, YANG G, FANG Y Y, et al. Analysis of nuclear magnetic resonance hydrogen spectral information of two wines[J]. Food Research and Development, 2023, 44(16): 157-161.
	金英今, 杨光, 方英玉, 等. 两种葡萄酒的核磁共振氢谱的信息分析[J]. 食品研究与开发, 2023, 44(16): 157-161.
[14]	LIU X Y, YAN W F, YANG G, et al. 1-hydroxy-7-azabenzotriazole-cinnamic esters as anti-Toxoplasma gondii agents[J]. Nat Prod Res, 2025: 1-7.
[15]	TIAN L. Molclus program: molclus_112_Win [CP/OL]. [2023-08-23]. http://www.keinsci.com/research/molclus.html.
[16]	LU T. A comprehensive electron wavefunction analysis toolbox for chemists, Multiwfn[J]. J Chem Phys, 2024, 161(8): 082503. doi: 10.1063/5.0216272
[17]	LU T, CHEN Q. Shermo: A general code for calculating molecular thermochemistry properties[J]. Comput Theor Chem, 2021, 1200: 113249. doi: 10.1016/j.comptc.2021.113249
[18]	KANEKO H, KORENAGA R, NAKAMURA R, et al. Binding characteristics of the doxepin E/Z-isomers to the histamine H1 receptor revealed by receptor-bound ligand analysis and molecular dynamics study[J]. J Mol Recognit, 2024, 37(5): e3098. doi: 10.1002/jmr.v37.5
[19]	ZHOU Q J, XIANG J F, TANG Y L. Applications of nuclear magnetic resonance spectroscopy in drug discovery[J]. Chinese J Magn Reson, 2010, 27(1): 68-79.
	周秋菊, 向俊锋, 唐亚林. 核磁共振波谱在药物发现中的应用[J]. 波谱学杂志, 2010, 27(1): 68-79.

Position	δ_H（化合物1实验值）	δ_H（化合物1计算值）	δ_H（化合物2实验值）	δ_H（化合物2计算值）
1(NH)	8.08		8.07
2	7.21	7.24	7.21	7.04
4	7.36	7.41	7.37	7.19
5	7.20	7.06	7.15	6.62
6	7.64	7.58	7.20	6.98
7	7.13	6.58	7.76	7.77
10	4.24	4.09	4.26	4.22
13	6.71	6.58	6.17	5.77
14	7.68	7.75	6.88	6.49
16	7.43	7.50	7.79	8.02
17	6.57	6.45	6.57	6.42
19	3.03	3.11	3.02	3.14

Position	δ_C（化合物1实验值）	δ_C（化合物1计算值）	δ_C（化合物2实验值）	δ_C（化合物2计算值）
2	123.0	125.8	123.1	122.5
3	110.4	109.9	110.6	108.6
4	111.3	111.1	111.3	109.3
5	122.4	120.7	122.3	120.6
6	119.8	120.4	119.8	118.6
7	119.2	117.7	119.4	117.8
8	136.4	134.9	136.4	137.9
9	127.3	126.1	127.4	126.2
10	22.9	22.5	22.8	24.9
11	169.9	174.0	169.8	174.0
12	176.3	177.7	176.2	177.1
13	104.9	101.6	105.0	100.6
14	143.0	144.6	142.4	143.8
15	122.4	122.9	122.6	121.2
16	129.7	133.0	132.7	130.8
17	112.0	117.1	111.3	110.6
18	151.9	148.8	151.4	148.2
19	40.3	40.3	40.3	40.3

顺/反-1,2,4-噁二唑衍生物的结构确证

Structure Elucidation of cis- and trans-1,2,4-Oxadiazol Derivatives

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