ORGANIC
LETTERS
2005
Vol. 7, No. 3
511-513
Enantioselective Route from
Carbohydrates to Cyclooctane Polyols
Leo A. Paquette* and Yunlong Zhang
EVans Chemical Laboratories, The Ohio State UniVersity, Columbus, Ohio 43210
Received December 14, 2004
ABSTRACT
A synthetic route to select cyclooctane-1,2,3-triols and 1,2,3,4,5-pentaols has been defined. The starting materials are D-glucose or D-arabinose,
and the key steps consist of a zirconocene-promoted ring contraction, a [3,3] sigmatropic rearrangement, and more extended functionalization
of the resulting cyclooctadienone.
Polysaccharides are recognized to mediate a host of cell
surface interactions, which include binding to toxins and
pathogens, and to form much of the structural framework of
cells and tissues. Such utilization of carbohydrates operates
widely despite long-recognized disadvantages associated with
unwelcomed hydrolytic instability, limitations linked to the
adoption of specific unfavorable conformations, and degrad-
ability brought on by glycosidases. As a result, carbohydrate
recognition events have been probed with polyhydroxylated
carbocyclic mimetics originally consisting of five- and six-
membered cyclitols.1 More recently, attention has been
increasingly accorded to eight-membered ring systems.2-6
The general perception is that replacement of the endocyclic
oxygen atom of a pyranoside ring by three methylene groups
would provide for unprecedented conformational projections
of the appended hydroxyl substituents while precluding
degradation by carbohydrate-processing enzymes. The prob-
ing of inhibitory activities toward glycosidases could be
meaningfully expanded as well.
(1) (a) Ogawa, S. In Carbohydrate Mimics, Concepts and Methods;
Chapleur, Y., Ed.; Wiley-VCH: Weinheim, 1998; pp 87-106. (b) Tang,
Y.-Q.; Maul, C.; Ho¨fs, R.; Sattler, I.; Grabley, S.; Feng, X.-Z.; Zeeck, A.;
Thiericke, R. Eur. J. Org. Chem. 2000, 149.
(2) (a) Ble´riot, Y.; Giroult, A.; Mallet, J.-M.; Rodriguez, E.; Vogel, P.;
Sinay¨, P. Tetrahedron: Asymmetry 2002, 13, 2553. (b) Wang, W.; Zhang,
Y.; Zhou, H.; Ble´riot, Y.; Sinay¨, P Eur. J. Org. Chem. 2001, 1053. (c)
Wang, W.; Zhang, Y.; Sollogoub, M.; Sinay¨, P. Angew. Chem., Int. Ed.
2000, 39, 2466.
(3) (a) van Hooft, P. A. V.; van der Marel, G. A.; van Boeckel, C. A.
A.; van Boom, J. H. Tetrahedron Lett. 2001, 42, 1769. (b) van Hooft, P.
A. V.; Litjens, R. E. J. N.; van der Marel, G. A.; van Boeckel, C. A. A.;
van Boom, J. H. Org. Lett. 2001, 3, 731.
Several years ago, our group reported on the discovery
that triisobutylaluminum (TIBAL) is capable of promoting
[3,3] sigmatropy within 2-methylene-6-vinyltetrahydropyrans
as a general route to functionalized eight-membered rings.7
(6) (a) McNulty, J.; Grunner, V.; Mao, J. Tetrahedron Lett. 2001, 42,
5609. (b) Gravier-Pelletier, C. A.; Andriuzzi, O.; Le Merrer, Y. Tetrahedron
Lett. 2002, 43, 245. (c) Fawcett, J.; Griffiths, G. A.; Percy, J. M.; Pintat,
S.; Smith, C. A.; Spencer, N. S.; Unemaya, E. Chem. Commun. 2002, 2828.
(4) Mehta, G.; Pallavi, K. Tetrahedron Lett. 2004, 45, 3865.
(5) (a) Boyer, F.-D.; Hanna, I.; Nolan, S. P J. Org. Chem. 2001, 66,
4094. (b) Hanna, I.; Ricard, L. Org. Lett. 2000, 2, 2651.
10.1021/ol0474296 CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/13/2005