菲诺洛芬的高效合成

doi:10.6023/cjoc202511013

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江苏 211816

收稿日期:2025-11-19 修回日期:2026-01-31
基金资助:
国家自然科学基金(No. 22071108)资助项目.

An Efficient Synthesis of Fenoprofen

Ma Yaopeng, Zhu Chenlong, Sun Bingfeng^*

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816

Received:2025-11-19 Revised:2026-01-31
Contact: ^*E-mail: bfsun@njtech.edu.cn
Supported by:
National Natural Science Foundation of China (No. 22071108)

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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,本文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。该项研究为相关药物的新工艺开发奠定了坚实基础。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是分子内过程,而非分子间过程,这与[1,2]氢迁移机理一致。

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, in agreement with the [1,2] hydride shift mechanism.

Key words: fenoprofen, NSAID, 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, doi: 10.6023/cjoc202511013.

Ma Yaopeng, Zhu Chenlong, Sun Bingfeng. An Efficient Synthesis of Fenoprofen[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202511013.

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参考文献

[1] (a) Brogden, R. N; Pinder, R. M.; Speight T. M.; Avery G. S. Drugs1977, 13, 241.(b) Lewis, J. R. J. Am. Med. Assoc. 1977, 237, 1260.
[2] (a) Bindu S.; Mazumder S.; Bandyopadhyay U. Bio. Pharm.2020, 180, 114147. (b) Harrington, P. J.; Lodewijk, E.Org. Process Res. Dev. 1997, 1, 72. (c) Ha, M. W.; Paek, S. M. Molecules 2021, 26, 4792. (d) Madhavi K.; Devi, B. K. Curr. Top. Med. Chem.2025, 25, 1185. (d) Madhavi, K.; Devi, B. K. Curr. Top. Med. Chem. 2025, 25, 1185.
[3] (a) Quann E. J.; Khwaja F.; Zavitz K. H.; Djakiew D. Cancer Res.2007 67, 3254. (b) Useini L.; Mojic M.; Laube M.; Lonnecke P.; Mijatovic S.; Maksimovic-Ivanic D.; Pietzsch J.; Hey-Hawkins E. ChemMedChem2023, 18, e202200583.
[4] (a) Galletti P.; Pori M.; Giacomini D. synlett2010, 17, 2644. (b) He Z.-T.; Hartwig, J. F. J. Am. Chem. Soc.2019, 141, 11749. (c) Shi, Y.; Kamer, P. C. J. Cole-Hamilton, D. J. Green Chem. 2019, 21, 1043. (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.; Wen-Ting Liu, W. -T.; Mei, H.; Meng, J.; Chen, J. -P. Chem. Commun. 2024, 60, 3854. (f) Qi, W.; Wang, Y.; Qiu, Y. Org. Lett. 2025, 27, 8440. (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. (i) Hu, J.; Lou, L.; Zhong, G. Huagong Shengchan Yu Jishu 2008, 15(6), 20.
[5] Chiang G. C. H.; Olsson T. Org. Lett.2004, 6, 3079.
[6] Yang Q.; Zhao Y.; Ma, D. Org. Process Res. Dev.2022, 26, 1690.
[7] Sone T.; Yamaguchi A.; Matsunaga S.; Shibasaki, M. J. Am. Chem. Soc.2008, 130, 10078.
[8] (a) Hock H.; Schrader O. Angew. Chem.1936, 49, 595.(b) Yaremenko, I. A.; Vil’, V. A.; Demchuk, D. V.; Terent’ev, A. O. Beilstein J. Org. Chem. 2016, 12, 1647.
[9] (a) Wagner G.; Brickner, W. Ber. Dtsch. Chem. Ges.1899, 32,2302. (b) Zhang X.; Tu Y.; Zhang F.; Chen Z.; Wang, S, Chem. Soc. Rev.2017, 46, 2272. For a relevant example from our early research, see: (c) Sun, B.; Xu, X. Tetrahedron Lett. 2006, 47, 299.