method has emerged and they behave very differently in
glycosylation reactions, their reactivity and selectivity being
strongly depended on the N protective group.14
The superarmed glucosamine derivatives 17 and 19 couple
very efficiently to glucose derivatives that are themselves
thioglycosides (Scheme 6).
These experiments proved that it is also possible to increase
the reactivity of a glucosamine donor through silylation with
bulky silyl protecting groups. The stereoelectronical effects from
the conformational change even overrules the unfavourable
electron withdrawing effect of the 6-OAc group (Scheme 6).
In conclusion, we have developed a quantitative method to
measure the rate of glycosylation reactions and demonstrated
that the difference in reactivity between the superarmed and
other donors is significant.
Scheme 4 Glycosylation with glucosamine acceptor.
Notes and references
1 (a) J. S. Debenham, R. Rodebaugh and B. Fraser-Reid, J. Org.
Chem., 1997, 62, 4591–4600; (b) H. M. Nguyen and J. L. Poole,
Angew. Chem., Int. Ed., 2001, 40, 414–416; (c) X. Huang, L.
Huang, H. Wang and X. S. Ye, Angew. Chem., Int. Ed., 2004,
43, 5221–5224; (d) K. M. Koeller and C.-H. Wong, Chem. Rev.,
2000, 100, 4465–4493; (e) S. V. Ley and H. W. M. Priepke, Angew.
Chem., Int. Ed. Engl., 1994, 33, 2292–2294; (f) N. L. Douglas, S. V.
Ley, U. Lucking and S. L. Warriner, J. Chem. Soc., Perkin Trans.
1, 1998, 51–65; (g) M. Lahmann and S. Oscarson, Org. Lett., 2001,
3, 4201–4204.
Scheme 5 One pot–one addition synthesis of trisaccharide 16.
As expected, one pot–one addition synthesis of the trisac-
charide 16 was performed and resulted in a good yield by a
sequential temperature activation of the donors (Scheme 5).
In order to differentiate between the relative reactivities of
donors and acceptors, an armed 6-OH acceptor 4 and a
disarmed 4-OH acceptor 15 were chosen as components in
the one pot glycosylation. The best yield was obtained when
having 1.1 eq. of superarmed donor 14 together with 1.2 eq. of
15 and activation at low temperature. This procedure is a
valuable method using the superarmed donors in oligosacchar-
ide one-pot synthesis, since in the literature the trend is to use a
stepwise addition of donor and acceptors.10
2 H. H. Jensen, C. M. Pedersen and M. Bols, Chem.–Eur. J., 2007,
13, 7576–7582.
3 (a) H. H. Jensen and M. Bols, Acc. Chem. Res., 2006, 39, 259–265;
(b) H. H. Jensen, L. Lyngbye, A. Jensen and M. Bols, Chem.–Eur.
J., 2002, 8, 1218–1226; (c) H. H. Jensen, L. Lyngbye and M. Bols,
Angew. Chem., Int. Ed., 2001, 40, 3447–3449; (d) H. H. Jensen and
M. Bols, Org. Lett., 2003, 5, 3201–3102.
4 (a) C. H. Marzabadi, J. E. Anderson, J. Gonzalez-Outeirino, P. R.
J. Gaffney, C. G. H. White, D. A. Tocher and L. J. Todaro, J. Am.
Chem. Soc., 2003, 125, 15163–15173; (b) J. Broddefalk, K.-E.
Bergquist and J. Kihlberg, Tetrahedron, 1998, 54, 12047–12070.
5 C. M. Pedersen, L. U. Nordstrøm and M. Bols, J. Am. Chem. Soc.,
2007, 129, 9222–9235.
As a part of our kinetic studies we were interested in
determining the relative rate of glucosaminyl donors, one
example being shown in Table 1, entry 13. Amino sugars are
known for their wide biological occurrence,11 including those
of the bacterial cell wall12 and the constitution of the core
pentasaccharide,13 but also for their potential biomedical
applications. There has been much research in developing
new methods for the synthesis of glucosamine derivatives in
the last decades. However, no general widely applicable
6 B. Fraser-Reid, Z. Wu, C. W. Andrews and E. Skowronski, J. Am.
Chem. Soc., 1991, 113, 1434–1435.
7 Z. Zhang, I. R. Ollmann, X.-S. Ye, R. Wischnat, T. Baasov and C.
H. Wong, J. Am. Chem. Soc., 1999, 121, 734–753.
8 (a) N. L. Douglas, S. V. Ley, U. Lucking and S. L. Warriner, J.
Chem. Soc., Perkin Trans. 1, 1998, 51–65; (b) M. Lahmann and S.
Oscarson, Can. J. Chem., 2002, 80, 889–893; (c) A. Bulow, T. Meyer,
T. K. Olszewski and M. Bols, Eur. J. Org. Chem., 2004, 323–329.
9 D. Crich and V. Dudkin, J. Am. Chem. Soc., 2001, 123, 6819–6825.
10 The field has recently been reviewed: (a) B. Yu, Z. Yang and H.
Cao, Curr. Org. Chem., 2005, 9, 179–194; (b) Y. Wang, L.-H.
Zhang and X.-S. Ye, Comb. Chem. High Throughput Screening,
2006, 9, 63–75. For examples: ; (c) X. Huang, L. Huang, H. Wang
and X.-S. Ye, Angew. Chem., Int. Ed., 2004, 43, 5221–5224; (d) J.
D. C. Codee, L. J. van den Bos, R. E. J. N. Litjens, H. S.
Overkleeft, J. H. van Boom and G. A. van der Marel, Org. Lett.,
2003, 5, 1947–1950; (e) S. V. Ley and H. W. M. Priepke, Angew.
Chem., Int. Ed. Engl., 1994, 33, 2292–2294; (f) H. Yamada, T.
Harada and T. Takahashi, J. Am. Chem. Soc., 1994, 116,
7919–7920; (g) M. Lahmann and S. Oscarson, Org. Lett., 2000,
2, 3881–3882.
11 (a) J. Banoub, P. Boullanger and D. Lafont, Chem. Rev., 1992, 92,
1167–1195; (b) S. Knapp, Chem. Soc. Rev., 1999, 28, 61–72.
12 D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry,
4th edn, 2005, pp. 245–252.
13 T. Buskas, S. Ingale and G.-J. Boons, Glycobiology, 2006, 16,
113R–136R.
14 A. F. G. Bongat and A. V. Demchenko, Carbohydr. Res., 2007,
342, 374–406.
Scheme 6 Glycosylations with very reactive glucosaminyl donors.
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 2465–2467 | 2467