An Approach to the Total Synthesis of Aphidicolin

An approach to the total synthesis of the tetracyclic diterpene antibiotic aphidicolin i is described. The key intermediate ii was prepared in 19 steps (3% overall yield) from 2-methoxybenzosuberone. The key step involved the solvolysis of a spire system (generated from a Claisen rearrangement) with participation of a remote double bond. The desired trans A/B ring fusion was introduced in the model system iii (18,19-dinoraphidicolan-3-one), available from alcohol ii in 7 steps (40% overall yield).