ORGANIC
LETTERS
2006
Vol. 8, No. 21
4883-4885
Total Synthesis of (±)-Clavubicyclone
Hisanaka Ito,* Shunta Takeguchi, Takahiro Kawagishi, and Kazuo Iguchi*
School of Life Sciences, Tokyo UniVersity of Pharmacy and Life Sciences,
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
itohisa@ls.toyaku.ac.jp; onocerin@ls.toyaku.ac.jp
Received August 6, 2006
ABSTRACT
The total synthesis of racemic clavubicyclone (1), which was isolated from Okinawan soft coral by our group, is described. The bicyclo[3.2.1]-
octane skeleton was prepared by Cope rearrangement of a divinylcyclopropane derivative. Three functional groups on the skeleton were
constructed by Barton decarboxylation, Wittig reaction, and alkylation.
Clavubicyclone (1) and tricycloclavulone were recently
isolated from Okinawan soft coral, ClaVularia Viridis, by
our group as novel prostanoid-related compounds which have
a bicyclo[3.2.1]octane skeleton (clavubicyclone) and a
tricyclo[5.3.0.01,4]decane skeleton (tricycloclavulone) (Figure
1).1 Although the planar structures and relative stereochem-
relative and absolute stereochemistries2 was attained. Clavu-
bicyclone (1), having a bicyclo[3.2.1]octane skeleton, two
side chains, and an acetoxyl group on the bridgehead
position, is a quite attractive synthetic target for organic
chemists. Therefore, effective construction of the bicyclic
core of 1 was examined, and we report herein the total
synthesis of (()-clavubicyclone (1).
Our strategy for the total synthesis of clavubicyclone (1)
focused on the use of Cope rearrangement of 4 to construct
the bicyclo[3.2.1]octane skeleton3,4 and Barton decarboxyl-
ation to create the bridgehead acetoxyl group (Scheme 1).
For the preparation of compound 4, aldol reaction of 6 with
dienolate and the following intramolecular cyclopropanation
using a Rh catalyst were employed. Conversion of the
methoxycarbonyl group of 3 to an acetoxyl group would be
achieved through Barton decarboxylation and the following
oxidation of the resulting radical intermediate by oxygen.
The construction of both side chains would achieve the total
synthesis of clavubicyclone (1).
Figure 1. The structures of marine prostanoid-related compounds,
clavubicyclone (1) and tricycloclavulone.
istries of the chiral centers on the cyclic cores were
determined by spectroscopic analysis, the stereochemistry
of the carbon bearing the acetoxyl group on the side chain
as well as the absolute stereochemistry had not yet been
examined. We recently achieved an enantioselective total
synthesis of tricycloclavulone, and the determination of the
(2) (a) Ito, H.; Kobayashi, T.; Hasegawa, M.; Iguchi, K. Tetrahedron
Lett. 2003, 44, 1259-1261. (b) Ito, H.; Hasegawa, M.; Takenaka, Y.;
Kobayashi, T.; Iguchi, K. J. Am. Chem. Soc. 2004, 126, 4520-4521.
(3) (a) Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C. Chem. ReV.
1989, 89, 165-198. (b) Doering, W. v. E.; Roth, W. R. Tetrahedron 1963,
19, 715-737. (c) Arai, M.; Crawford, R. J. Can. J. Chem. 1972, 50, 2158-
2162. (d) Baldwin, J. E.; Gilbert, K. E. J. Am. Chem. Soc. 1976, 98, 8283-
8284.
(4) For an example of a synthesis of natural product through Cope
rearrangement of divinylcyclopropane, see: Fukuyama, T.; Liu, G. J. Am.
Chem. Soc. 1996, 118, 7426-7427.
(1) Iwashima, M.; Terada, I.; Okamoto, K.; Iguchi, K. J. Org. Chem.
2002, 67, 2977-2981.
10.1021/ol061947u CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/13/2006