Total Synthesis of the Marine Polyketide (−)-Gracilioether F

First asymmetric synthesis of the marine natural product (−)-gracilioether F is described from a d-mannitol derived known compound. The key step involves intramolecular 1,4-conjugate addition of a hydroxymethyl radical generated from Ti (III) mediated ring opening of a terminal epoxy ring tethered to a butenolide to produce stereoselectively a five-membered ring fused bicyclic lactone, the core structure present in gracilioether F.