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<p>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 <i>via</i> 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.</p><p></p>

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Synthesis of tetrahydroisoquinoline-fused polycyclic heterocyclic skeletons via Vilsmeier-reagent promoted decarbonylative annulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月27日

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  • Mengdi Yan,
  • Umit Mukatay,
  • Hui Shen,
  • Jiming Sun,
  • Ruohan Zhang,
  • Jina Sun,
  • Jing Li,
  • Kaixian Chen,
  • Jian Li,
  • Hong Liu

摘要

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.