Total Synthesis of (±)-Fasicularin through Double Consecutive Epimerizations.

The total synthesis of tricyclic marine alkaloid fasicularin ( 1b ) has been accomplished from a novel sterically well-defined α-aminonitrile 7 , featuring a novel double consecutive epimerization process and Ir-catalyzed reductive functionalization of a tertiary γ-lactam. The required configuration is obtained through the thermodynamically stereoselectively driven isomerization of a readily available 8a-cyanodecahydroquinoline framework. The strategy allows us to achieve the tricyclic core structures efficiently from affordable starting materials through simple operations.