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.