Metal‐Free [3 + 3] and [4 + 2] Cascade Cyclization of Dihydroisoquinolines and Ene‐Yne‐Oxazolones: Synthesis of Indenoisoquinolinoquinolinamides

A cascade cyclization of polycyclic indenoisoquinolinoquinolinamides has been realized via metal-free [3 + 3] and [4 + 2] intramolecular cyclization of ene-yne-oxazolones and dihydroisoquinoline under neutral conditions in good to excellent yield. In this process, three rings and four bonds are formed with high atom economy under reaction conditions that comply with green chemistry principles. The biological activity of the indenoisoquinolinoquinolinamide analogs, which mimic the structure of lamellarins-a group of marine natural products-was evaluated. The results indicated that these indenoisoquinolinoquinolinamide analogs exhibited notable anti-cancer activity, with cytotoxicity profiles comparable to those of their lamellarin counterparts.