Methodological Development and Applications of Tryptamine-Ynamide Cyclizations in Synthesizing Core Skeletons of Indole Alkaloids.

Over the past two decades, synthetic strategies for synthesizing the skeletons of various indole alkaloids based on tryptamine-ynamide have been continuously developed and applied to the total syntheses or formal total syntheses of related molecules. In this synopsis, we summarized the cyclization pathways of tryptamine-ynamide under different catalytic conditions, emphasizing the reaction mechanism and applications in the syntheses of indole alkaloids.

Gold(I)-Catalyzed Tandem Intramolecular Methoxylation/Double Aldol Condensation Strategy Yielding 2,2'-Spirobi[indene] Derivatives.

The syntheses of 2,2'-spirobi[indene] derivatives based on a gold(I)-catalyzed tandem strategy involving intramolecular methoxylation/double aldol condensation were achieved. Examination of the scope of this tandem reaction by using a batch of alkynone substrates disclosed that the reaction possessed a good functional group tolerance. A cationic gold(I) catalyst/protonic acid-catalyzed mechanism for this tandem reaction is proposed.

Total Syntheses of Aspidospermidine, N-Methylaspidospermidine, N-Acetylaspidospermidine, and Aspidospermine via a Tandem Cyclization of Tryptamine-Ynamide.

The total syntheses of aspidospermidine, N-methylaspidospermidine, N-acetylaspidospermidine, and aspidospermine were achieved from a common pentacyclic indoline intermediate. The common pentacyclic indoline intermediate was synthesized on a gram scale through a Stork-enamine alkylation of 1H-pyrrolo[2,3-d]carbazole derivatives, which were prepared through a Brønsted acid-catalyzed tandem cyclization of tryptamine-ynamide. The scalable synthesis of 1H-pyrrolo[2,3-d]carbazole afforded facile access and a practical approach to the Aspidosperma indole alkaloid family.