Syntheses of Structurally Complex Marine Cyclopropyl‐Diterpenoids: Peyssonnoside A and Its Aglycon

Peyssonnoside A is a marine‐derived sulfated diterpenoid glucoside featuring a remarkable 5/6/3/6 tetracyclic skeleton with a highly substituted cyclopropane ring deeply embedded in its structure. Herein, we report on the full development of the first total synthesis of this natural product and its aglycon, peyssonnosol. Through the experimental evaluation of a series of synthetic strategies, including utilization of Ohloff–Rautenstrauch cycloisomerization and C−H allylation, we identified a concise, efficient, and highly diastereoselective route. Key steps in the synthesis of the aglycone peyssonnosol include a Simmons–Smith cyclopropanation and a Mukaiyama hydration, both guided by the inherent spatial features of the substrates. This optimized approach enabled the synthesis of peyssonnosol in 12 steps and 21 % overall yield and provides a robust framework for accessing structurally complex marine natural products.