ORGANIC
LETTERS
2009
Vol. 11, No. 12
2699-2701
Facile and Efficient Synthesis of
Naturally Occurring Carbasugars
(+)-Pericosines A and C†
Yoshihide Usami,* Marie Ohsugi, Koji Mizuki, Hayato Ichikawa, and
Masao Arimoto
Osaka UniVersity of Pharmaceutical Sciences, 4-20-1 Nasahara,
Takatsuki, Osaka 569-1094, Japan
Received April 15, 2009
ABSTRACT
An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which
is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective
bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-
pericosine C and also to a synthesis of (-)-pericosine C.
The isolation of pericosines A-E, 1-5, respectively, as
cytotoxic metabolites of Periconia byssoides OUPS-N133
originally separated from the sea hare, Aplysia kurodai, was
reported in 1997 and 2007.1,2 Because this series of
compounds have a multifunctionalized cyclohexene core that
is typical of carbasugars,3,4 we have been interested in their
syntheses and the synthesis of their related compounds.5-9
Among them, pericosine A (1) is the most important one
because it was reported to possess significant inhibitory
activity against protein kinase EGFR (epidermal growth
factor receptor) and human topoisomerase II in addition to
antitumor activity against P388 in vivo.2 The absolute
configurations of 1-4 were determined by their total
syntheses.6-8,10 However, the overall yields in the first total
synthesis of (-)- and (+)-1 were not satisfactory, although
the absolute configuration of natural 1 was elucidated.7
† This paper is dedicated to Professor Kaoru Fuji on the occasion of his
retirement from Hiroshima International University.
(1) Numata, A.; Iritani, M.; Yamada, T.; Minoura, K.; Matsumura, E.;
Therefore, we desired to devise a more efficient synthetic
route for (+)-1 in the hope that it could be amenable to the
construction of analogues. Naturally occurring pericosine C
(3) was reported to be an enantiomeric mixture,2 and we
have reported the synthesis of (+)-3,6 which exists as a minor
component in nature. We are also interested in the synthesis
of (-)-3.
Yamori, T.; Tsuruo, T. Tetrahedron Lett. 1997, 38, 8215–8218
(2) Yamada, T.; Iritani, M.; Ohishi, H.; Tanaka, K.; Doi, M.; Minoura,
K.; Numata, A. Org. Biomol. Chem. 2007, 5, 3979–3986
(3) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. ReV. 2007,
107, 1919–2036
(4) Sanchez-Abella, L.; Fernandez, S.; Armesto, N.; Ferrero, M.; Gotor,
V. J. Org. Chem. 2006, 71, 5396–5399
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(5) Usami, Y.; Ichikawa, H.; Arimoto, M. Int. J. Mol. Sci. 2008, 9, 401–
421
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(6) Usami, Y.; Hatsuno, C.; Yamamoto, H.; Tanabe, M.; Numata, A.
Chem. Pharm. Bull 2004, 52, 1130–1133; Erratum Chem. Pharm. Bull. 2005,
(8) Usami, Y.; Mizuki, K.; Ichikawa, H.; Arimoto, M. Tetrahedron:
Asymmetry 2008, 19, 1460–1463
(9) Usami, Y.; Suzuki, K.; Mizuki, K.; Ichikawa, H.; Arimoto, M. Org.
Biomol. Chem. 2009, 7, 315–318
(10) Donohoe, T. J.; Blades, K.; Helliwell, M.; Warning, M. J.;
Newcombe, N. J. Tetrahedron Lett. 1998, 39, 8755–8758
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53, 271
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(7) Usami, Y.; Takaoka, I.; Ichikawa, H.; Horibe, Y.; Tomiyama, Y.;
.
Otsuka, M.; Imanishi, Y.; Arimoto, M. J. Org. Chem. 2007, 72, 6127–
6134
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.
10.1021/ol9008188 CCC: $40.75
Published on Web 05/27/2009
2009 American Chemical Society