|
|
四氢异喹啉衍生物合成吡咯并二氢异喹啉化合物研究进展
|
Abstract:
吡咯并异喹啉衍生物是一类重要的含氮杂环化合物，具有显著的抗肿瘤活性，其众多合成中间体亦表现出良好的生物活性，因而受到化学、生物及医学领域研究者的广泛关注。近年来，以四氢异喹啉衍生物为原料合成吡咯并二氢异喹啉及其类似物的研究日趋活跃，文章对此类合成策略的主要研究进展进行了概括和总结，以期为吡咯并异喹啉衍生物的合成及应用研究提供借鉴。
Pyrroloisoquinoline derivatives constitute an important class of nitrogen-containing heterocyclic compounds known for their remarkable antitumor activity. Many of their synthetic intermediates also exhibit favorable biological activities, attracting widespread attention from researchers in chemistry, biology, and medicine. In recent years, studies on the synthesis of pyrrolodihydroisoquinolines and their analogs using tetrahydroisoquinoline derivatives as starting materials have become increasingly active. This paper summarizes the major research advances in relevant synthetic strategies, providing a reference for the synthesis and application of pyrroloisoquinoline derivatives.
| [1] | Mitsiou, V.M., Antonaki, A.N., Douka, M.D. and Litinas, K.E. (2024) An Overview on the Synthesis of Lamellarins and Related Compounds with Biological Interest. Molecules, 29, Article No. 4032. https://doi.org/10.3390/molecules29174032 |
| [2] | Wei, M., Chen, J., Song, Y., Monserrat, J., Zhang, Y. and Shen, L. (2024) Progress on Synthesis and Structure-Activity Relationships of Lamellarins over the Past Decade. European Journal of Medicinal Chemistry, 269, Article ID: 116294. https://doi.org/10.1016/j.ejmech.2024.116294 |
| [3] | Yu, C., Zhang, Y., Zhang, S., Li, H. and Wang, W. (2011) Cu(II) Catalyzed Oxidation-[3+2] Cycloaddition-Aromatization Cascade: Efficient Synthesis of Pyrrolo[2,1-a]isoquinolines. Chemical Communications, 47, 1036-1038. https://doi.org/10.1039/c0cc03186k |
| [4] | Huang, H.M., Li, Y.J., Ye, Q., Yu, W., Han, L., Jia, J., et al. (2014) Iodine-Catalyzed 1,3-Dipolar Cycloaddition/Oxidation/Aromatization Cascade with Hydrogen Peroxide as the Terminal Oxidant: General Route to Pyrrolo[2,1-a]isoquinolines. The Journal of Organic Chemistry, 79, 1084-1092. https://doi.org/10.1021/jo402540j |
| [5] | Basavaiah, D., Lingaiah, B., Reddy, G.C. and Sahu, B.C. (2016) Baylis-Hillman Acetates in Synthesis: Copper(I)/Tert‐Butyl Hydroperoxide Promoted One‐Pot Oxidative Intramolecular Cyclization Protocol for the Preparation of Pyrrole‐Fused Compounds and the Formal Synthesis of (±)‐Crispine A. European Journal of Organic Chemistry, 2016, 2398-2403. https://doi.org/10.1002/ejoc.201600384 |
| [6] | Shang, Z.-H., Zhang, X.-J., Li, Y.-M., Wu, R.-X., et al. (2021) One-Pot Synthesis of Chromone-Fused Pyrrolo[2,1-a]isoquinolines and Indolizino[8,7-b]indoles: Iodine-Promoted Oxidative [2+2+1] Annulation of o-Acetylphenoxyacrylates with Tetrahydroisoquinolines and Noreleagnines. The Journal of Organic Chemistry, 86, 15733-15742. https://doi.org/10.1021/acs.joc.1c01682 |
| [7] | Xu, H., Zhang, K., Zhang, L., Zhang, Y., Sun, J., Li, Y., et al. (2026) Synthesis of 1,3-Diaryl-5,6-dihydropyrrolo[2,1-a]isoquinolines via Copper-Promoted Reaction of Tetrahydroisoquinolines with Α,β-Unsaturated Ketones under Solvent-Free Conditions. Tetrahedron, 194, Article ID: 135178. https://doi.org/10.1016/j.tet.2026.135178 |
| [8] | Zhang, B.-H., Hou, K.-L., Li, R.-Z., et al. (2025) A One-Pot Synthesis of Substituted Pyrrolo[2,1-a]isoquinolines via an Oxidation/Annulation Sequence of 2-(3,4-Dihydroisoquinolin-2(1h)-yl)malononitriles. The Journal of Organic Chemistry, 90, 7134-7144. https://doi.org/10.1021/acs.joc.5c00639 |
| [9] | Deb, I. and Seidel, D. (2010) Retro-Claisen Condensation versus Pyrrole Formation in Reactions of Amines and 1,3-Diketones. Tetrahedron Letters, 51, 2945-2947. https://doi.org/10.1016/j.tetlet.2010.03.086 |
| [10] | Liu, S., Ma, D., Zhu, X., Luo, C., Tan, H., Ju, X., et al. (2020) Iron Catalyzed [3+2] Cycloaddition of Tetrahydroisoquinoline: Synthesis of Dihydropyrrolo[2,1‐a]isoquinolines. Asian Journal of Organic Chemistry, 9, 1617-1622. https://doi.org/10.1002/ajoc.202000211 |
| [11] | Yang, Z., Lu, N., Wei, Z., Cao, J., Liang, D., Duan, H., et al. (2016) Base-Promoted Intermolecular Cyclization of Substituted 3-Aryl(heteroaryl)-3-chloroacrylaldehydes and Tetrahydroisoquinolines: An Approach to Access Pyrrolo[2,1-a]isoquinolines. The Journal of Organic Chemistry, 81, 11950-11955. https://doi.org/10.1021/acs.joc.6b01781 |
| [12] | Zhang, Y., Zhao, W., Hou, G., Liu, L. and Li, J. (2023) Synthesis of 5,6-Dihydropyrrolo[2,1-a]isoquinolines via a Tfa-Promoted Annulation of Arylpropiolaldehydes and 1,2,3,4-Tetrahydroisoquinolines. Tetrahedron Letters, 120, Article ID: 154458. https://doi.org/10.1016/j.tetlet.2023.154458 |
| [13] | Agarwal, S., Kataeva, O., Schmidt, U. and Knölker, H.-J. (2013) Silver(I)-Promoted Oxidative Cyclisation to Pyrrolo[2,1-a]isoquinolines and Application to the Synthesis of (±)-Crispine A. RSC Advances, 3, 1089-1096. https://doi.org/10.1039/c2ra22823h |
| [14] | Herr, P., Glaser, F., Büldt, L.A., Larsen, C.B. and Wenger, O.S. (2019) Long-Lived, Strongly Emissive, and Highly Reducing Excited States in Mo(0) Complexes with Chelating Isocyanides. Journal of the American Chemical Society, 141, 14394-14402. https://doi.org/10.1021/jacs.9b07373 |
| [15] | Zheng, K.L., You, M.Q., Shu, W.M., et al. (2017) Acid-Mediated Intermolecular [3+2] Cycloaddition toward Pyrrolo[2,1-a]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G Trimethyl Ether. Organic Letters, 19, 2262-2265. https://doi.org/10.1021/acs.orglett.7b00769 |
| [16] | Zhuang, S.-Y., Liu, J.-Y., Guo, H., Tang, Y., Chen, X., Ma, J., et al. (2022) I2-DMSO Mediated Multicomponent [3+2] Annulation Reaction: An Approach to Pyrrolo[2,1-a]isoquinoline Derivatives with a Quaternary Center. Organic Letters, 24, 8573-8577. https://doi.org/10.1021/acs.orglett.2c03651 |
| [17] | Jiang, M., Sheng, X., Luo, Y. and Cui, H. (2025) Copper-Catalyzed Synthesis of Pyrrolo[2,1-a]isoquinolines through Condensation/Cycloaddition/Aromatization Cascade. Tetrahedron Letters, 173, Article ID: 155829. https://doi.org/10.1016/j.tetlet.2025.155829 |
| [18] | Zou, Y., Lu, L., Fu, L., Chang, N., Rong, J., Chen, J., et al. (2011) Visible‐Light‐Induced Oxidation/[3+2] Cycloaddition/Oxidative Aromatization Sequence: A Photocatalytic Strategy to Construct Pyrrolo[2,1‐a]isoquinolines. Angewandte Chemie International Edition, 50, 7171-7175. https://doi.org/10.1002/anie.201102306 |
| [19] | Huang, L. and Zhao, J. (2013) C60-Bodipy Dyad Triplet Photosensitizers as Organic Photocatalysts for Photocatalytic Tandem Oxidation/[3+2] Cycloaddition Reactions to Prepare Pyrrolo[2,1-a]isoquinoline. Chemical Communications, 49, Article No. 3751. https://doi.org/10.1039/c3cc41494a |
| [20] | Fujiya, A., Tanaka, M., Yamaguchi, E., Tada, N. and Itoh, A. (2016) Sequential Photo-Oxidative [3+2] Cycloaddition/Oxidative Aromatization Reactions for the Synthesis of Pyrrolo[2,1-a]isoquinolines Using Molecular Oxygen as the Terminal Oxidant. The Journal of Organic Chemistry, 81, 7262-7270. https://doi.org/10.1021/acs.joc.6b00439 |
| [21] | Rana, P., Udari, G., Sridhar, B. and Prakash Singh, S. (2023) Fullerene C70 as Photoredox Catalyst for the Synthesis of Pyrrolo[2,1‐a]isoquinolines by 1,3‐Dipolar Cycloaddition‐Aromatization Sequence. Chemistry—A European Journal, 29, e202203354. https://doi.org/10.1002/chem.202203354 |
| [22] | Wang, Q., Yuan, T., Liu, Q., Xu, Y., Xie, G., Lv, X., et al. (2019) External Oxidant-Free Oxidation/[3+2] Cycloaddition/Aromatization Cascade: Electrochemical Synthesis of Polycyclic N-Heterocycles. Chemical Communications, 55, 8398-8401. https://doi.org/10.1039/c9cc04336e |
