ORGANIC
LETTERS
2000
Vol. 2, No. 20
3135-3138
The Mild Cleavage of
2-Amino-2-deoxy-D-glucoside
Methoxycarbonyl Derivatives
Bryan K. S. Yeung, Sara L. Adamski-Werner, Jennifer B. Bernard,
Gae1lle Poulenat, and Peter A. Petillo*
Department of Chemistry, UniVersity of Illinois at Urbana-Champaign,
600 South Mathews AVenue, Urbana, Illinois 61801
Received July 15, 2000
ABSTRACT
The conversion of methyl carbamate to the corresponding free amine is described for a series of 2-amino-2-deoxy-D-glucosamine derivatives.
Cleavage of methoxycarbonyl moiety with MeSiCl3 and triethylamine in dry THF at 60 °C and subsequent aqueous hydrolysis yields the free
amine in 54 to 93% yields. The selective cleavage of methyl carbamates with MeSiCl3 in the presence of a 2,2,2-trichloroethoxycarbonyl group
or 2-azido glycosides affords selectively, orthogonal N-deprotected carbohydrates.
N-Acetylglucosamine-containing oligosaccharides are ubiq-
uitous in biological systems and are major constituents of
mucopolysaccharides, peptidoglycans, glycoproteins, and
blood group antigens.1 Consequently, and because of their
biological importance, N-acetylglucosamine oligosaccharides
are important synthetic targets.2 In general, the successful
chemical synthesis of these species requires careful selection
of the N-protecting group on the 2-amino-2-deoxy sugar that
is compatible with the glycosylation methodology employed
and is readily removed in the presence of other carbohydrate
functionality. In general, 2-acetamido glycoside derivatives
are not directly employed because of poor solubility in
organic solvents, and formation of the methyloxazoline3 is
oftentimes the major product isolated, thus making them poor
glycosyl donors.4
carbamates is limited in generality and scope.5 For example,
methoxycarbonyl has not been widely employed, as N-
deprotection typically involves a strong base and/or elevated
reaction temperatures.6 However, recent reports demonstrated
that the methoxycarbonyl moiety is readily cleaved in the
presence of a Lewis acid such as TMSI,7 HSiCl3,8,9 or H2-
SiI2.10 Additionally, different chlorosilanes were shown to
activate carbamates differently, leading to multilevel selectiv-
ity in the cleavage of carbamates to isocyanates.9 This latter
(4) A one-pot glycosylation method was recently reported with methyl-
oxazolines as glycosyl donors. See: Di Bussolo, V.; Liu, J.; Huffman, L.
G.; Gin, D. Y. Angew. Chem., Int. Ed. 2000, 1, 204.
(5) (a) Green, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 2nd ed.; John Wiley & Sons: New York, 1991; pp 315-348.
(b) Kocienski, P. J. Protecting Groups; Georg Thiem Verlag: Stuttgart,
1994. (c) Shapiro, G.; Marzi, M. J. Org. Chem. 1997, 62, 7096. (d) Ozaki,
S. Chem. ReV. 1972, 72, 457. (e) Valli, V. L. K.; Alper, H. J. Org. Chem.
1995, 60, 257.
(6) A single report exists on the base-induced cleavage of methoxycar-
bonyl monosaccharide derivatives. See: Kobayashi, Y.; Tsuchiya, T.; Ohgi,
T.; Taneichi, N.; Koyama, Y. Carbohydr. Res. 1992, 230, 89.
(7) (a) Lott, R. S.; Chauhan, V. S.; Stammer, C. H. J. Chem. Soc., Chem.
Commun. 1979, 495. (b) Raucher, S.; Bray, B. L.; Lawrence, R. F. J. Am.
Chem. Soc. 1987, 109, 442. (c) Kende, A. S.; Luzzio, M. J.; Mendoza, J.
S. J. Org. Chem. 1990, 55, 918.
Carbamates that act as protecting groups find widespread
use in the synthesis of N-acetylglucosamine-containing
oligosaccharides.2 Among these, CBz- and TROC-carbam-
ates are commonly employed, although the use of other
(1) Carbohydrate Chemistry; Kennedy, J. F., Ed.; Oxford University
Press: Oxford, 1988.
(2) Yeung, B. K. S.; Chong, P. Y.; Petillo, P. A. The Synthesis of
Glycosaminoglycans. In Glycochemistry: Principles, Synthesis and Ap-
plications; Bertozzi, C., Wang, G., Eds.; Marcel-Dekker, in press.
(3) Banoub, J.; Boullanger, P.; Lafont, D. Chem. ReV. 1992, 92, 1167.
(8) (a) Greber, G.; Kricheldorf, H. R. Angew. Chem., Int. Ed. Engl. 1968,
7, 941. (b) Pirkle, W. H.; Hauske, J. R. J. Org. Chem. 1977, 42, 2781. (c)
Pirkle, W. H.; Hoekstra, M. S. J. Org. Chem. 19747, 39, 3904. (d) Pirkle,
W. H.; Rinaldi, P. L. J. Org. Chem. 1978, 43, 3808.
10.1021/ol0063353 CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/09/2000