Abstract:

Quassinoids are degraded triterpenoids whose dense stereochemical arrays and polycyclic architectures have presented longstanding challenges in total synthesis. In our approach to bruceantin, the most eminent congener of the family, we demonstrate that the tricarbocyclic core bearing oxygenation at all requisite carbons can be rapidly assembled through an MHAT-initiated annulation. Subsequent studies revealed unanticipated reactivity of highly elaborated tetracyclic intermediates, highlighting the challenges posed by the early introduction of the extensive oxygenation pattern seen in bruceantin.