A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B.
Ahmad K HaidarNiels D KjeldsenNikolaj S TroelsenViola PrevitaliKasper P LundquistThomas O LarsenMads Hartvig ClausenPublished in: Molecules (Basel, Switzerland) (2022)
Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11-17 steps, 1.5-2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.