Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

Over the past decades, aspidosperma and kopsia alkaloids have attracted significant interest by the organic synthetic community owing to their intricate fused-ring structures and broad biological activities. Consequently, numerous strategically distinct total syntheses have been accomplished, among which tetracyclic pyridocarbazoles have seen widespread adoption as versatile building blocks. In this review, we elaborate and discuss the synthesis of such tetracyclic pyridocarbazoles according to the different approaches for the establishment of the all-carbon quaternary center at C5. This includes (1) classic synthetic reactions (cycloaddition, Michael addition, nucleophilic substitution, and Claisen rearrangement), (2) palladium-catalyzed asymmetric decarboxylative allylation reactions, and (3) thiourea-catalyzed asymmetric Michael addition reactions. Furthermore, we also describe the late-stage key transformations in the realm of the total syntheses of aspidosperma and kopsia alkaloids.

Automated summary

This review discusses the synthesis of tetracyclic pyridocarbazoles, focusing on different approaches for establishing the all-carbon quaternary center at C5. Classic synthetic reactions, palladium-catalyzed asymmetric decarboxylative allylation reactions, and thiourea-catalyzed asymmetric Michael addition reactions have been employed. Late-stage key transformations in the total syntheses of aspidosperma and kopsia alkaloids are also described.