Synthesis of tetracyclic spiroindolines by an interrupted Bischler-Napieralski reaction: total synthesis of akuammicine

Judicious substrate design allows interruption of the classical Bischler-Napieralski reaction, providing access to a range of diversely substituted tetracyclic spiroindolines. These complex polycyclic scaffolds are valuable building blocks for the construction of indole alkaloids, as showcased in a concise total synthesis of (±)-akuammicine. The interrupted Bischler-Napieralski reaction of β,γ-unsaturated tryptamides affords tetracyclic spiro pyrroloindolines, which can be used in the total synthesis of the Strychnos alkaloid, akuammicine.