Abstract
The tetrahydroisoquinoline scaffold is an important structural motif in many natural products and pharmaceuticals, known for its broad biological activities. Fused tetrahydroisoquinoline polycyclic heterocyclic structures have increasingly attracted attention, yet their synthetic pathways remain limited. Herein, we developed an efficient, metal-free strategy for assembling tetrahydroisoquinoline-fused polycycles via Vilsmeier-reagent promoted decarbonylative cyclization reaction. The protocol features mild conditions, excellent functional-group tolerance, and high efficiency. Furthermore, biological evaluations demonstrated that the constructed derivatives exhibit antiproliferative activity in cancer cell lines, thereby providing potential starting points for further optimization.
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Data availability
Detailed experimental procedures and characterizations of new compounds are available in Supplementary Information and Supplementary Data 1–4. The X-ray crystallographic coordinates for structures reported in this Article have been provided as Supplementary Data 1 and 2 and have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition numbers CCDC 2446305 (2a) and 2446312 (4r). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (Nos. 22377138 and 22337003).
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Conceptualization: Jian Li, Kaixian Chen, Jing Li, and Hong Liu; methodology: Mengdi Yan, Umit Mukatay, Hui Shen, Jiming Sun, and Jina Sun; investigation: Mengdi Yan, Umit Mukatay, Hui Shen, Jiming Sun, and Ruohan Zhang; writing—original draft: Mengdi Yan and Jian Li; writing—review and editing: Kaixian Chen, Jian Li, and Hong Liu; funding acquisition: Kaixian Chen and Hong Liu; resources: Jina Sun, Jian Li, and Hong Liu; supervision: Jian Li and Hong Liu.
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Yan, M., Mukatay, U., Shen, H. et al. Synthesis of tetrahydroisoquinoline-fused polycyclic heterocyclic skeletons via Vilsmeier-reagent promoted decarbonylative annulation. Commun Chem (2026). https://doi.org/10.1038/s42004-026-01982-z
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DOI: https://doi.org/10.1038/s42004-026-01982-z
