Work

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

Year: 2026

Type: article

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. Tetrahydroisoquinoline scaffolds are crucial in natural products and pharmaceuticals due to their diverse biological activities, yet synthetic pathways for their polycyclic forms are limited. Here, the authors present a metal-free, Vilsmeier-reagent promoted decarbonylative cyclization method, yielding derivatives with notable antitumor activity.

Source: Communications Chemistry

DOI: 10.1038/s42004-026-01982-z