Total Synthesis of (±)-Berkeleyone A.

A 13-step total synthesis of the fungal meroterpenoid berkeleyone A is reported. The molecular skeleton is formed using the first examples of two critical construction reactions: (1) an epoxide-initiated, β-ketoester-terminated polycyclization, and (2) an isomerization-cyclization cascade to generate the remaining bicyclo[3.3.1]nonane framework. The resulting 6-step synthesis of the carbocyclic core of the berkeleyone natural products has been used to access protoaustinoid A and berkeleyone A, and will aid future biosynthetic investigations into the origin of related natural products.