Enantioselective Synthesis of Euonyminol

We describe an enantioselective total
synthesis of the nonahydroxylated
sesquiterpenoid euonyminol, the dihydro-β-agarofuran nucleus
of the macrocyclic terpenoid alkaloids known as the cathedulins. Key
features of the synthetic sequence include a highly diastereoselective
intramolecular alkene oxyalkylation to establish the C10 quaternary
center, an intramolecular aldol–dehydration to access the tricyclic
scaffold of the target, a tandem lactonization–epoxide opening
to form the trans-C2–C3 vicinal diol residue,
and a late-stage diastereoselective α-ketol rearrangement. The
synthesis provides the first synthetic access to enantioenriched euonyminol
and establishes a platform to synthesize the cathedulins.