Total Synthesis of Acorane-Type Sesquiterpenes (±)-Bilaiaeacorenol B and (±)-Penicibilaenes A and B.

The synthesis of acorane-type tricyclic sesquiterpenes (±)-bilaiaeacorenol B (1; R = H, X = OH) and (±)-penicibilaenes A (2; R = X = H) and B (3; R = Ac, X = H) is described. The strategy is chemically driven by bridgehead enone chemistry and relies primarily on two key tactics: (1) assembly of ring A through diastereoselective intramolecular aldol cyclization of a functionalized bicyclic building block bearing a crucial bridgehead all-carbon quaternary center; and (2) construction of ring C via ring contraction through sequential diol oxidative cleavage and subsequent regioselective intramolecular aldol condensation of a functionalized tricyclic intermediate possessing all six requisite relative configurations. The present study reports the first total synthesis of (±)-bilaiaeacorenol B and an alternative synthesis of (±)-penicibilaenes A and B, which showcase the synthetic potential of bridgehead enone chemistry.