Isoquinolones in Polycyclic Alkaloids: Structures, Bioactivities, and Synthetic Strategies

Isoquinolone is an important heterocycle and key pharmacophore in numerous bioactive molecules, including natural products and small‐molecule drugs. The fusion of the isoquinolone core with other cyclic skeletons generates significant structural diversity, exemplified by oxyberberine‐, nauclea‐, rosettacin‐, and oxynitidine‐type alkaloids, as well as clinically investigated small‐molecule inhibitors, such as indotecan (LMP400) and indimitecan (LMP776). This review systematically discusses the synthesis of ring‐fused isoquinolones, with a particular focus on natural products containing these scaffolds. The organization is based on key transformative reactions, including photo and radical cyclization, base‐mediated cyclization, and transition‐metal‐catalyzed cross‐coupling/C–H activation. By providing a unified discussion of diverse isoquinolone alkaloids and drugs, this review aims to draw attention to advances in synthetic methodologies and the structural diversity inherent to the isoquinolone core, thereby encouraging future investigations into isoquinolone‐based drug discovery.