Total Synthesis of (-)-Verrucarol(1).
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 alpha-methylated gamma-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 epsilon-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.
Ishihara
Jun
J
Department of Applied Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223, Japan.
Nonaka
Rie
R
Terasawa
Yuki
Y
Shiraki
Ryota
R
Yabu
Kazuo
K
Kataoka
Hiromi
H
Ochiai
Yuichi
Y
Tadano Ki
Kin-ichi