(-)-加兰他敏的简洁全合成：一种高效的碱促进内酰胺化策略

doi:10.6023/cjoc202512039

研究论文

(-)-加兰他敏的简洁全合成：一种高效的碱促进内酰胺化策略

刘则琳^a, 何泗泉^a, 阿迪拉·阿布都热西提^a, 金钟^b,*

^a喀什大学化学与环境科学学院新疆喀什 844006;
^b新疆大学化学学院新疆乌鲁木齐 830046

收稿日期:2026-12-26 修回日期:2026-03-04
基金资助:
国家自然科学基金(Nos. 22171145、32560660); 新疆人才发展基金项目(XJRC-2025-KJ-YJ-CXPT-146); 新疆维吾尔自治区自然科学基金(No. 2024D01A13); 喀什大学创新研究团队计划资助项目.

Concise Total Synthesis of (-)-Galanthamine: An Efficient Base-Promoted Lactamization Strategy

Liu Zelin^a, He Siquan^a, Adila Abudurexiti^a, Jin Zhong^b,*

^aCollege of Chemistry and Enviromental Sciences, Kashi University, Kashi 844006, China;
^bCollege of Chemistry, Xinjiang University, Urumqi 830046, China

Received:2026-12-26 Revised:2026-03-04
Contact: *E-mail: zjin@nankai.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 22171145; 32560660); the Talent Development Project of Xinjiang Uygur Autonomous Region (XJRC-2025-KJ-YJ-CXPT-146); Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2024D01A13); Program for Innovative Research Team in Kashi University.

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摘要/Abstract

开发了一种以容易制备的3-(6-氧代环己-1-烯-1-基)丙酸乙酯3为起始原料的高效内酰胺化策略, 用于(-)-加兰他敏1的简洁全合成. 该策略经简短的反应步骤以19.2%的总收率获得了天然植物药(-)-加兰他敏. 该策略的特点在于采用了氢化钠促进芳醛和N-氨基甲酸酯之间的分子内氧化酰胺化反应合成关键的苯并氮杂䓬环, 具有反应条件温和，操作简便的优点.

关键词: (-)-加兰他敏, 分子内氧化内酰胺化, 全合成, 阿尔茨海默病

An efficient lactamization strategy using ethyl 3-(6-oxocyclohex-1-en-1-yl)propanoate (3) as the starting material for concise total synthesis of (-)-galanthamine (1) is presented. Naturally occurring phytomedicine (-)-galanthamine was obtained with a total yield of 19.2% in concise steps. This approach features a mild and convenient intramolecular oxidative amidation reaction between aromatic aldehyde and N-carbamate promoted by sodium hydride for synthesis of the key benzo[c]azepine ring.

Key words: (-)-galanthamine, intramolecular oxidative amidation, total synthesis, Alzheimer’s disease

引用此文

刘则琳, 何泗泉, 阿迪拉·阿布都热西提, 金钟. (-)-加兰他敏的简洁全合成：一种高效的碱促进内酰胺化策略[J]. 有机化学, doi: 10.6023/cjoc202512039.

Liu Zelin, He Siquan, Adila Abudurexiti, Jin Zhong. Concise Total Synthesis of (-)-Galanthamine: An Efficient Base-Promoted Lactamization Strategy[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202512039.

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参考文献

[1] (a) Jin Z.; Yang H.-D.; Xu X.-H.; Yao, G.-M. In Natural Products, Eds. Ramawat, K. G.; Mérillon, J.-M. Springer-Verlag GmbH Germany, part of Springer Nature2025, Chapter 18. (b) Jin, Z.; Yao, G.-M.Nat. Prod. Rep. 2019, 36, 1462.
[2] (a) Scott L. J.; Goa K. L. Drugs2000, 60, 1095.(b) Prvulovic D.; Hampel H.; Pantel, J. Expert. Opin. Drug Met.2010, 6, 345.
[3] Cheng B.; Wang Q.; Chen, F. Nat. Prod. Rep.2024, 41, 1060.
[4] Marco-Contelles J.; do Carmo Carreiras M.; Rodriguez C.; Villarroya M.; Garcia, A. G. Chem. Rev.2006, 106, 116.
[5] (a) Trost B. M.; Toste, F. D. J. Am. Chem. Soc.2000, 122, 11262. (b) Trost, B. M.; Tang, W.Angew. Chem. Int. Ed. 2002, 41, 2795. (c) Guillou C.; Beunard J.-L.; Gras E.; Thal, C. Angew. Chem. Int. Ed.2001, 40, 4745.
[6] (a) Miller I. R.; Mclean N. J.; Moustafa G. A. I.; Ajavakom V.; Kemp S. C.; Bellingham R. K.; Camp N. P.; Brown, R. C. D. J. Org. Chem.2022, 87, 1325. (b) Satcharoen V.; McLean N. J.; Kemp S. C.; Camp N. P.; Brown, R. C. D. Org. Lett.2007, 9, 1867.
[7] Nugent J.; Matousova E.; Banwell M. G.Eur. J. Org. Chem. 2015, 3771.
[8] Hu X.-D.; Tu Y.-Q.; Zhang E.; Gao S.; Wang S.; Wang A.; Fan C-A.; Wang M. Org. Lett.2006, 8, 1823.
[9] Zhang Q.; Zhang F.-M.; Zhang C.-S.; Liu S.-Z.; Tian J.-M.; Wang S.-H.; Zhang X.-M.; Tu, Y.-Q. J. Org. Chem.2019, 84, 12664.
[10] Chen P.; Bao X.; Zhang L.-F.; Ding M.; Han X.-J.; Li J.; Zhang G.-B.; Tu Y.-Q.; Fan, C.-A. Angew. Chem. Int. Ed.2011, 50, 8161.
[11] Chen J.-Q.; Xie J.-H.; Bao D.-H.; Liu S.; Zhou Q.-L. Org. Lett.2012, 14, 2714.
[12] Li L.; Yang Q.; Wang Y.; Jia, Y. Angew. Chem. Int. Ed.2015, 54, 6255.
[13] (a) Liu C.-H.; Yu, Z.-X. Org. Biomol. Chem.2016, 14, 5945.(b) Feng Y.; Yu Z.-X.J. Org. Chem. 2015, 80, 1952.
[14] Zhang Y.; Shen S.; Fang H.; Xu T. Org. Lett.2020, 22, 1244.
[15] Chang Y.-P.; Ma X.; Shao H.; Zhao Y.-M. Org. Lett.2021, 23, 9659.
[16] For selected examples, (a) Xiong Z.; Weidlich F.; Sanchez C.; Wirth, T. Org. Biomol. Chem.2022, 20, 4123.(b) Pollok D.; Großmann L. M.; Behrendt T.; Opatz T.; Waldvogel, S. R. Chem. Eur. J.2022, 28, e202201523. (c) Kodama, S.; Hamashima, Y.; Nishide, K.; Node, M.Angew. Chem. Int. Ed. 2004, 43, 2659.(d) Node, M.; Kodama, S.; Hamashima, Y.; Baba, T.; Hamamichi, N.; Nishide, K. Angew. Chem. Int. Ed. 2001, 40, 3060., 6625.
[17] (a) Pal S.; Majumder S.; Niyogi S.; Shyamal P.; Mondal D.; Das, B. Bisai A.Chem. Sci. 2024, 15, 19851.(b) Hu, N.; He, Y.-T.; Lan, P.; Banwell, M. G.; White, L. V. Aust. J. Chem. 2022, 75, 974., 2016.(d) Magnus P.; Sane N.; Fauber B. P.; Lynch, V. J. Am. Chem. Soc.2009, 131, 16045.
[18] (a) Qiu J.-Y.; Zeng W.-L.; Xie H.; Wang W-Y.; Li, W. Angew. Chem. Int. Ed.2023, 62, e202218961. (b) Majumder, S.; Yadav, A.; Pal, S.; Khatua, A.; Bisai, A.J. Org. Chem. 2022, 87, 7786. (c) Venkatesh T.; Mainkar P. S.; Chandrasekhar, S. Org. Biomol. Chem.2019, 17, 2192. (d) Ishikawa, T.; Kudo, K.; Kuroyabu, K.; Uchida, S.; Kudoh, T.; Saito, S.J. Org. Chem. 2008, 73, 7498.
[19] (a) Küenburg B.; Czollner L.; Fröhlich J.; Jordis U.Org. Process Res. Dev. 1999, 3, 425.(b) Czollner, L.; Frantsits, W.; Küenburg, B.; Hedenig, U.; Fröhlich, J.; Jordis, U. Tetrahedron Lett. 1998, 39, 2087.
[20] Hwu J. R.; Hakimelahi G. H.; Chou C. T.Tetrahedron Lett. 1992,33, 6469.
[21] Ishihara K.; Yano T.Org. Lett. 2004, 6, 1983.
[22] Wang X.; Wang D. Z. Tetrahedron2011, 67, 3406.
[23] Zhang H.; Xu N.; Su B.; Zhang J.; Zhang C.; Zhang Z.; Guo B.; Xu S.; Wang S.; Rang, R. J. Org. Chem.2024, 89, 7579.
[24] Kulkarni S. S.; Hu X.; Manetsch R. Chem. Commun.2013, 49, 1193.
[25] Fischer J.; Savage G.P.; Coster, M. J. A. Org. Lett.2011, 13, 3376.