B. Vauzeilles et al. / Tetrahedron Letters 42 (2001) 7567–7570
7569
OH
O
OH
O
NHAc
NHAc
OR
HO
HO
O
HO
HO
O
O
O
HO
O
NH
NHAc
OH
OH
O
O
16 R = H
17 R = allyl
Scheme 4.
tetramer or pentamer), no dissolving was observed after
4 h of stirring in DMF, and virtually no transforma-
tion could be detected by TLC (entries 3, 5 and 8, Table
). Chitin fragments are notoriously insoluble and solu-
References
2
1. (a) Feizi, T. Curr. Opin. Struct. Biol. 1993, 3, 107; (b)
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2
bility has always been recognized as a major problem in
their chemical transformation in aprotic or protic sol-
2
5
a
vents. DMSO as a solvent resulted in a modest
improvement leading to selectively allylated chitotetra-
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1
9% respectively, entries 6 and 9, Table 2). Solubility
remained an issue affecting both yield and reproducibil-
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topentaose were however solubilized in the DMF-LiBr
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with good yields (57–68%) and selectivities (a:b ratio of
1
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3
4
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6-9:1) as shown in Table 2 (entries 4, 7 and 10). Finally,
the Boc-protected tetramer 16 was converted to allyl
glycosides 17 (entry 11, Table 2 and Scheme 4).
2
(
The solubilizing effect of salts is well documented both
in polysaccharide chemistry, where N,N-dimethylacet-
amide with LiCl was originally developed to dissolve
1
5
1
3
14
6
chitin , cellulose or other polysaccharides, and in
peptide chemistry where Seebach has shown that addi-
tion of lithium salts greatly increases solubility of pep-
1
5
tides in ether solvents. We further observe a salt effect
on stereoselectivity with an apparent increase in the
reactivity of the b-alkoxide which suggests that discrete
complexes may be formed and this important aspect is
currently being considered.
7
8
We have shown that direct anomeric O-alkylation pro-
vides a fast, efficient and selective synthesis of gly-
9
cosides of N-acetyl
D-glucosamine and derivatives
useful as building blocks in carbohydrate chemistry,
together with an easy derivatization procedure for chi-
16
tooligosaccharides. This procedure should also prove
useful in the synthesis of glycosides of other bioactive
oligosaccharides for biological research.
9
2, 1167; (c) For a recent example, see: Kamst, E.;
Zegelaar-Jaarsveld, K.; van der Marel, G. A.; van Boom,
J. A.; Lugtenberg, B. J. J.; Spaink, H. P. Carbohydr. Res.
1
999, 321, 176.
0. For this experiment, N-acetyl
2 equiv.) were suspended in DMF (1 mL per mmol of 1)
1
D-glucosamine 1 and LiBr
Acknowledgements
(
under argon. This suspension was stirred at room temper-
ature until a homogeneous solution was obtained (1 h),
after which sodium hydride (1.3 equiv.) and allyl bromide
We are grateful to Drs H. Driguez and E. Samain for
supplying the chitooligosaccharides. This work was
supported by grants from the Centre National de la
Recherche Scientifique (Physique et Chimie du Vivant
program) and the European Communities (Training
and Mobility of Researchers Program, contract no.
ERBFMRX-CT98-0243).
(
3 equiv.) were added.
11. D e´ nari e´ , J.; Debell e´ , F.; Prom e´ , J.-C. Annu. Rev.
Biochem. 1996, 65, 503.
12. Nishimura, S.-I.; Kuzuhara, H.; Takiguchi, Y.; Shima-
hara, K. Carbohydr. Res. 1989, 194, 223.