1014
J . Org. Chem. 2001, 66, 1014-1017
Notes
Sch em e 1
En a n tioselective Syn th esis of Op tica lly
Active Ca r bocyclic Su ga r s
Nicholas Gathergood, Kristian Rahbek Knudsen, and
Karl Anker J ørgensen*
Center for Metal Catalyzed Reactions, Department of
Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark
kaj@kemi.aau.dk.
Received October 2, 2000
In tr od u ction
Optically active carbocyclic sugars, having various
types of biological activity, are important analogues of
sugars.1 These properties can be due to the carbocyclic
sugar itself or the incorporation of the carbosugar frag-
ment into other molecules. The presence of carbocyclic
sugars in biologically active compounds includes the
natural carbocyclic nucleosides such as aristeromycin2
and neplanocin A,3 which display antibiotic and antitu-
mor activity. Synthetic carbocyclic nucleosides with
important therapeutic properties have also been devel-
oped,4 including carbovir5 and structurally related com-
pounds.6
The most widely used synthetic procedures for the
preparation of optically active carbocyclic sugars are (i)
modification of abundant optically pure compounds,
usually carbohydrates, to the carbosugar structure7 and
(1) For a review see, e.g., Crimmins, M. T. Tetrahedron 1998, 54,
9229.
(2) Kusaka, T.; Yamamoto, H.; Shibata, M.; Muroi, M.; Kishi, T.;
Mizuno; K. J . Antibiot. 1968, 21, 255.
(3) Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi, M.;
Otani, M. J . Antibiot. 1981, 34, 359.
(4) See, e.g., (a) J acobs, G. A.; Tino, J . A.; Zahler, R. Tetrahedron
Lett. 1989, 30, 6955. (b) Slusarchyk, W. A.; Young, M. G.; Bisacchi, G.
S.; Hockstein, D. R.; Zahler, R. Tetrahedron Lett. 1989, 30, 6453. (c)
Diaz, M.; Ortuno, R. M. Tetrahedron: Asymmetry 1997, 20, 3421. (d)
Ezzitouni, A.; Barchi, J . J ., J r.; Marquez, V. E. J . Chem. Soc., Chem.
Commun. 1995, 1345. (e) Biggadike, K.; Borthwick, A. D.; Exall, A.
M.; Kirk, B. E.; Roberts, S. M.; Youlds, P. J . Chem. Soc., Chem.
Commun. 1987, 1083. (f) Biggadike, K.; Borthwick, A. D.; Exall, A.
M.; Kirk, B. E.; Roberts, S. M.; Youlds, P.; Slawin, A. M. Z.; Williams,
D. J . J . Chem. Soc., Chem. Commun. 1987, 255. (g) Morizawa, Y.;
Nakayama, T.; Matsumura, Y.; Uchida, K.; Yasuda, A. Bull. Chem.
Soc. J pn. 1993, 66, 2714. (h) Ahmed, S. Tetrahedron Lett. 1991, 32,
6997. (i) Antle, V. D.; Caperelli, C. A. Nucleosides Nucleotides 1999,
18, 1911. (j) Comin, M. J .; Pujol, C. A.; Damonte, E. B.; Rodriguez, J .
B. Nucleosides Nucleotides 1999, 18, 2219.
(5) See, e.g., (a) Vince, R.; Hua, M. J . Med. Chem. 1990, 33, 17. (b)
Trost, B. M.; Madsen, R.; Guile, S. D.; Brown, B. J . Am. Chem. Soc.
2000, 122, 5947. (c) J ones, M. F.; Myers, P. L.; Robertson, C. A.; Storer,
R.; Williamson, C. J . Chem. Soc., Perkin Trans. 1 1991, 2479.
(6) See, e.g., (a) Katagiri, N.; Nomura, M.; Sato, H.; Kaneko, C.;
Yusa, K.; Tsutuo, T. J . Med. Chem. 1992, 35, 1882. (b) Hildbrand, S.;
Leumann, C.; Scheffold, R. Helv. Chim. Acta 1996, 79, 702. (c) Daluge,
S. M. U.S. Patent 5,034,394, 1991
(ii) synthesis by modification of achiral or racemic start-
ing materials.8
This paper presents a simple enantioselective approach
for the preparation of the optically active carbocyclic
sugars 1a -f using cyclopentadiene as the carbon frag-
ment (Scheme 1). All of the stereogenic centers in 1a -f
are directed by the two stereogenic centers in 3 intro-
duced by an asymmetric hydroboration reaction of a
substituted cyclopentadiene, prepared from cyclopenta-
diene 2. It is possible to prepare both enantiomers of the
hydroborating reagent used for the preparation of 3, and
thus the other enantiomer of 3 is also easily accessible.
Alcohol 3 has been prepared before and is known as a
(8) (a) Marschner, C.; Baumgartner, Griengl, H. J . Org. Chem. 1995,
60, 5224. (b) Yakura, T.; Ueki, A.; Kitamura, T.; Tanaka, K.; Nameki,
M.; Ikeda, M. Tetrahedron 1999, 55, 7461. (c) Landis, Y.; Rapado, P.
Eur. J . Org. Chem. 2000, 401. (d) Bodenteich, M.; Marquez, V. E.
Tetrahedron 1992, 48, 5961. (e) Desire, J .; Prandi, J . Tetrahedron Lett.
1997, 38, 6189.
(7) (a) Horneman, A. M.; Lundt, I.; Søtofte, I. Synlett 1995, 918. (b)
Horneman, A. M.; Lundt, I. Tetrahedron 1997, 53, 6879. (c) Callam,
C. S.; Lowary, T. L. Org. Lett. 2000, 2, 167. (d) Horneman, A. M.; Lundt,
I. J . Org. Chem. 1998, 63, 1919. (e) J ohansen, S. K.; Lundt, I. J . Chem.
Soc., Perkin Trans. 1 1999, 3615.
10.1021/jo001427r CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/10/2001