Expedited Total Synthesis of (±)-Brevianamide A via the Strategic Use of Gold(I) Catalysis

Two concise and complementary routes to the polycyclic alkaloid (+/-)-brevianamide A from readily available amino acid building blocks are presented. Key to the synthesis is the strategic use of a gold(I)-catalyzed cascade process that quickly assembles the characteristic pseudoindoxyl motif of the natural product along with the two adjacent quaternary centers in a single step. This sequence, which exemplifies the structural complexity that can be achieved with gold catalysis, allowed for the shortest and highest-yield synthesis of (+/-)-brevianamide A to date (four steps LLS, 14% overall yield).

Automated summary

Two concise and complementary routes to the polycyclic alkaloid (+/-)-brevianamide A from readily available amino acid building blocks are presented. The key to the synthesis is the strategic use of a gold(I)-catalyzed cascade process, which quickly assembles the characteristic pseudoindoxyl motif of the natural product and the two adjacent quaternary centers in a single step. This sequence exemplifies the structural complexity achievable with gold catalysis and allows for the shortest and highest-yield synthesis of (+/-)-brevianamide A to date.