We have achieved the total synthesis of (−)-verrucarol, a
trichothecene sesquiterpenoid obtained
as a hydrolysis product of the naturally occurring verrucarin A.
Our total synthesis began with
the previously reported enantiomerically pure bicyclic α-methylated
γ-lactone, which was prepared
from d-glucose. The key steps for the total synthesis
were (1) aldol-like carbon−carbon bond
formation applied to the starting lactone using a four-carbon aldehyde
as an electrophile for
introduction of the quaternary stereogenic carbon sharing the B and
C-rings of the trichothecene
skeleton, (2) Dieckmann cyclization of the derived ε-ester lactone
for construction of the C-ring
equivalent, (3) Barton's decarboxylative oxygenation for conversion of
a carboxylic acid functionality
in the Dieckmann cyclization product into a hydroxyl group, (4)
skeletal enlargement strategy for
the crucial trichothecene skeleton construction, and (5) the final
stereoselective formation of the
exo-epoxy ring at the methylene carbon in the bridge
constituting the B and C-rings.