Sequential Dieckmann cyclization enables the total synthesis of 7--clusianone and 18-hydroxy-7--clusianone

A unified approach for the construction of the bicyclo[3.3.1]nonane-2,4,9-trione core of polycyclic polyprenylated acylphloroglucinols (PPAPs) was reported. This approach involves a sequential process of two distinct Dieckmann condensation reactions from the linear precursor. Using this method, the divergent total synthesis of the natural products 7- epi -clusianone and 18-hydroxy-7- epi -clusianone and the formal synthesis of sampsonione P were achieved. Additionally, other key steps to realize this strategy include RuCl 3 -catalyzed oxidative olefin cleavage and Pd-catalyzed Tsuji-Trost decarboxylative allylation. The synthesis indicated that bicyclo[3.3.1]nonane-2,4,9-triones could also be constructed via 6-membered intermediates. We established a protocol for constructing the core of polycyclic polyprenylated acylphloroglucines. This protocol facilitated the synthesis of 7- epi -clusianone, 18-hydroxy-7- epi -clusianone, and sampsonione P via a 6-membered intermediate.