Total Synthesis of Tetracyclic Spirooxindole Alkaloids via a Double Oxidative Rearrangement/Cyclization Cascade

Skeleton rearrangement could rapidly
transfer simple molecules
to complex structures and has significant potential in the total synthesis
of natural products. We developed a one-pot reaction cascade of double
oxidative rearrangement of furan and indole followed by a nucleophilic
cyclization that was successfully applied for the formal synthesis
of rhynchophylline/isorhynchophylline and the first total synthesis
of (±)-7(R)-geissoschizol oxindole/(±)-7(S)-geissoschizol oxindole. In addition, the geissoschizol
oxindoles were revised to their C3 epimers, and the mechanism for
the reversed stereochemistry through the retro-Mannich/Mannich cascade
was proposed and supported by density functional theory calculations.