菲诺洛芬的高效合成

doi:10.6023/cjoc202511013

有机化学 ›› 2026, Vol. 46 ›› Issue (5): 2036-2043.DOI: 10.6023/cjoc202511013 上一篇下一篇

研究论文

菲诺洛芬的高效合成

马耀鹏, 朱辰龙, 孙炳峰^*()

南京工业大学药学院南京 211816

收稿日期:2025-11-19 修回日期:2026-01-31 发布日期:2026-02-28
通讯作者: 孙炳峰
基金资助:
国家自然科学基金(22071108)

An Efficient Synthesis of Fenoprofen

Yaopeng Ma, Chenlong Zhu, Bingfeng Sun^*()

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816

Received:2025-11-19 Revised:2026-01-31 Published:2026-02-28
Contact: Bingfeng Sun
Supported by:
National Natural Science Foundation of China(22071108)

文章分享

1. 262036S.pdf(1725KB)

摘要/Abstract

菲诺洛芬(fenoprofen)属于芳基丙酸类非甾体抗炎药物, 其供应依赖于化学合成. 以Corey-Chaykovsky环氧化反应和三氟化硼催化的半频哪醇重排反应为关键反应, 实现了菲诺洛芬的高效合成. 该合成法也适用于ibuprofen、hexaprofen、biprofen的合成, 为这类药物新型合成工艺的开发提供了有力依据. 研究证实该半频哪醇重排反应是分步进行的; 同位素实验表明, 该重排反应属于分子内反应, 而非分子间反应, 与[1,2]氢迁移反应机理一致.

关键词: 菲诺洛芬, 非甾体抗炎药, 半频哪醇重排, 高效合成

An efficient synthesis of fenoprofen has been successfully achieved, featuring a Corey-Chaykovsky epoxidation reaction and a BF₃-catalyzed semi-pinacol rearrangement reaction. This newly developed protocol is amenable to the syntheses of ibuprofen, hexaprofen and biprofen. This research provides a solid basis for further development of novel processes for the production of these pharmaceutically important molecules. The semi-pinacol rearrangement reaction was a stepwise process. The isotope-labeling experiments indicated that this rearrangement took place intramolecularly rather than intermolecularly, matching the [1,2]-hydride shift mechanism.

Key words: fenoprofen, nonsteroidal anti-inflammatory drug, semi-pinacol rearrangement, efficient synthesis

引用此文

马耀鹏, 朱辰龙, 孙炳峰. 菲诺洛芬的高效合成[J]. 有机化学, 2026, 46(5): 2036-2043.

Yaopeng Ma, Chenlong Zhu, Bingfeng Sun. An Efficient Synthesis of Fenoprofen[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2036-2043.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 12

参考文献 9

[1]	(a) Brogden R. N.; Pinder R. M.; Speight T. M.; Avery G. S. Drugs 1977, 13, 241. pmid: 324748
	(b) Lewis J. R. J. Am. Med. Assoc. 1977, 237, 1260. doi: 10.1001/jama.1977.03270390076033 pmid: 324748
[2]	(a) Bindu S.; Mazumder S.; Bandyopadhyay U. Biochem. Pharmacol. 2020, 180, 114147. doi: 10.1016/j.bcp.2020.114147
	(b) Harrington P. J.; Lodewijk E. Org. Process Res. Dev. 1997, 1, 72. doi: 10.1021/op960009e
	(c) Ha M. W.; Paek S. M. Molecules 2021, 26, 4792. doi: 10.3390/molecules26164792
	(d) Madhavi K.; Devi B. K. Curr. Top. Med. Chem. 2025, 25, 1185. doi: 10.2174/0115680266334717241127043711
[3]	(a) Quann E. J.; Khwaja F.; Zavitz K. H.; Djakiew D. Cancer Res. 2007 67, 3254. doi: 10.1158/0008-5472.CAN-06-3657
	(b) Useini L.; Mojic M.; Laube M.; Lonnecke P.; Mijatovic S.; Maksimovic-Ivanic D.; Pietzsch J.; Hey-Hawkins E. ChemMed- Chem 2023, 18, e202200583.
[4]	(a) Galletti P.; Pori M.; Giacomini D. Synlett 2010, 17, 2644.
	(b) He Z.-T.; Hartwig J. F. J. Am. Chem. Soc. 2019, 141, 11749. doi: 10.1021/jacs.9b03291
	(c) Shi Y.; Kamer P. C. J.; Cole-Hamilton D. J. Green Chem. 2019, 21, 1043. doi: 10.1039/C8GC03823F
	(d) Yuan P.-F.; Yang Z.; Zhang S.-S.; Zhu G.-M.; Yang X.-L.; Meng Q.-Y. Angew. Chem., Int. Ed. 2024, 63, e202313030.
	(e) Guo C.-Y.; Chen J.-Z.; Liu W.-T.; Mei H.; Meng J.; Chen J.-P. Chem. Commun. 2024, 60, 3854. doi: 10.1039/D3CC06018G
	(f) Qi W.; Wang Y.; Qiu Y. Org. Lett. 2025, 27, 8440. doi: 10.1021/acs.orglett.5c02243
	(g) Zhang S.; Zong Y.; Qian Y.; Zhang J.; Chen G.-Q.; Zhang X. Green Synth. Catal. 2025, 6, 119.
	(h) Acetti D.; Brenna E.; Fronza G.; Fuganti C. Talanta 2008, 76, 651. doi: 10.1016/j.talanta.2008.04.009
	(i) Hu J.; Lou L.; Zhong G. Chem. Prod. Technol. 2008, 15, 20 (in Chinese).
	(胡金清, 楼良弟, 钟光祥, 化工生产与技术, 2008, 15, 20.)
[5]	Chiang G. C. H.; Olsson T. Org. Lett. 2004, 6, 3079. pmid: 15330592
[6]	Yang Q.; Zhao Y.; Ma D. Org. Process Res. Dev. 2022, 26, 1690. doi: 10.1021/acs.oprd.2c00050
[7]	Sone T.; Yamaguchi A.; Matsunaga S.; Shibasaki M. J. Am. Chem. Soc. 2008, 130, 10078. doi: 10.1021/ja803864p
[8]	(a) Hock H.; Schrader O. Angew. Chem. 1936, 49, 595. doi: 10.1002/ange.v49:31 pmid: 27559418
	(b) Yaremenko I. A.; Vil’ V. A.; Demchuk D. V.; Terent'ev A. O. Beilstein J. Org. Chem. 2016, 12, 1647. doi: 10.3762/bjoc.12.162 pmid: 27559418
[9]	(a) Wagner G.; Brickner W. Ber. Dtsch. Chem. Ges. 1899, 32, 2302. doi: 10.1002/cber.v32:2
	(b) Zhang X.; Tu Y.; Zhang F.; Chen Z.; Wang S. Chem. Soc. Rev. 2017, 46, 2272. doi: 10.1039/C6CS00935B
	For a relevant example from our early research, see:
	(c) Sun B.; Xu X. Tetrahedron Lett. 2006, 47, 299. doi: 10.1016/j.tetlet.2005.11.021

Entry	9/ equiv.	Cu(OAc)₂/ equiv.	Pyridine/ equiv.	Additive	Yield^b/%
1	2	2	2	N₂	19
2	2	2	2	Air	24
3	2	2	2	O₂	90
4	1.5	1.5	2	O₂	87
5	1.5	1.5	1.5	O₂	79

Entry	9/ equiv.	Cu(OAc)₂/ equiv.	Pyridine/ equiv.	Additive	Yield^b/%
1	2	2	2	N₂	19
2	2	2	2	Air	24
3	2	2	2	O₂	90
4	1.5	1.5	2	O₂	87
5	1.5	1.5	1.5	O₂	79

Entry	[Cu]	Base	Solvent	Yield^b/%
1	CuI	K₂CO₃	DMSO	46
2	CuI	K₃PO₄	DMSO	65
3	CuI	K₃PO₄	DMF	36
4	CuBr	K₃PO₄	DMSO	49
5	CuCl	K₂CO₃	DMSO	42
6	Cu powder	K₂CO₃	DMSO	40
7	Cu powder	K₂CO₃	DMF	83

Entry	[Cu]	Base	Solvent	Yield^b/%
1	CuI	K₂CO₃	DMSO	46
2	CuI	K₃PO₄	DMSO	65
3	CuI	K₃PO₄	DMF	36
4	CuBr	K₃PO₄	DMSO	49
5	CuCl	K₂CO₃	DMSO	42
6	Cu powder	K₂CO₃	DMSO	40
7	Cu powder	K₂CO₃	DMF	83

Entry	Salt	Base	Solvent	T/℃	t/h	Yield^b/%
1	Me₃S^＋I^－	NaH	DMSO/THF	r.t.	2	95
2	Me₃S^＋I^－	KOH	DMSO/THF	r.t.	15	87
3	Me₃S(O)Br	NaH	DMSO/THF	r.t.	36	71
4	Me₃S^＋Br^－	KOH	MeCN	r.t.	32	87
5	Me₃S^＋Br^－	NaOMe	MeCN	r.t.	32	73
6	Me₃S^＋Br^－	NaOH	MeCN	r.t.	32	66
7	Me₃S^＋Br^－	KOH	MeCN	60	3	93
8	Me₃S^＋Br^－	KOH	MeCN/H₂O	60	3	93

菲诺洛芬的高效合成

An Efficient Synthesis of Fenoprofen

RichHTML

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

图/表 12

参考文献 9

相关文章 2

编辑推荐

相关统计

本文评价

Entry	Cat. (equiv.)	Solvent	Additive	Yield ^b/%
Entry	Cat. (equiv.)	Solvent	Additive	5	11	7
1	TsOH (0.01)	THF	O₂	13	39	43
2	TsOH (0.01)	THF	N₂	65	27	<5
3	CSA (0.01)	DCM	O₂	9	47	39
4	CSA (0.01)	DCM	N₂	41	33	21
5	BF₃ (0.01)	DCM	N₂	88	—	—
6	BF₃ (0.1)	THF	N₂	90	—	—
7	BF₃ (0.5)	THF	N₂	93	—	—

[1]	刘晶晶, 张东辉, 江伟男, 刘润辉. Fmoc-DOPA(acetonide)-OH的简单高效合成[J]. 有机化学, 2020, 40(8): 2543-2546.
[2]	陈志龙,吴毓林,伍贻康. (S)-2-芳基丙酸不对称合成研究进展[J]. 有机化学, 2002, 22(1): 22-32.