Abstract:

This presentation will describe our progress towards a total synthesis of a rare isocyanoterpene (ICT) natural product, neoamphilectane. Within the ICT family, neoamphilectane is one of the only members yet to succumb to synthetic efforts and its biological activity remains unknown. Additionally, its spirocyclic ring system that is unlike any other amphilectane has prompted our exploration of alternative methods for its synthesis. We have investigated numerous annulation methodologies for the construction of the tricyclic scaffold, which revealed multiple unexpected polycyclization reactions and rearrangements of complex intermediates. Currently, our efforts have led to a concise 9-step synthesis of the core of the natural product from (+)-dihydrocarvone. Future work is aimed at a strategy involving late-stage electrophilic methylation of a secondary isocyanide whose substrate synthesis efforts will be discussed.