LETTER
Influence of Protecting Groups on the Reactivity of chiro-Inositol Glycosyl Acceptors
2055
in 2 mL of CH Cl under argon and stirred at r.t. for 30 min, then
4.30–4.20 (m, 3 H, H or H , H , H ), 4.18 (t, 1 H, J = 9.9 Hz, H ),
2
2
4
3
2
5
3a¢
0
–
.1 equiv (60 mL of a 0.1 M solution) of TMSOTf were added at
25 °C. After stirring the reaction mixture for 1 h, it was quenched
3.97 (t, 1 H, J = 9.9 Hz H ), 3.73–3.38 (m, 8 H, 2 H , 2 H6b¢¢, H4b¢¢,
4a¢ 6a¢
H2b¢¢, H3b¢¢, H5b¢¢), 3.17 (dd, 1 H, J = 10.0, 3.5 Hz, H2a¢).
with Et N, concentrated and purified by flash chromatography
3
Competitive experiments of aceptors 8–11 with trichloroacetimi-
date donor 10 were carried out from a equimolecular mixture of
trichloroacetimidate (0.024 mmol) and acceptors (0.024 mmol) as
described in the preparation of 18 and 22, adding 0.1 equiv of
TMSOTf at –25 °C, in CH Cl (1 mL) and stirring the reaction
(
(
hexane–EtOAc, 4:1 to 2:1) to yield 13 mg (18%) of 18 and 5 mg
7%) of 22.
2
0
Data of a(1→1) pseudodisaccharide 18: [a]D +70.6 (c 0.6,
1
CHCl ). H NMR (500 MHz, CDCl ): d = 7.96 (d, 2 H, J = 8.0 Hz,
3
3
2
2
Hortho), 7.91 (d, 2 H, J = 8.0 Hz, Hortho), 7.87 (d, 2 H, J = 8.0 Hz,
Hortho), 7.85 (d, 2 H, J = 8.0 Hz, Hortho), 7.50–7.00 (m, 15 H, 3 Bn
mixture for 1 h.
and 12 H, 4 Bz), 6.23 (t, 1 H, J = 9.9 Hz, H ), 6.16 (t, 1 H, J = 9.9
4
Acknowledgment
Hz, H ), 5.90–5.85 (m, 2 H, H and H ), 5.05 (d, 1 H, J = 3.6 Hz,
3
5
2
H ), 5.00–4.07 (3 AB syst., 6 H), 4.63 (br s, 1 H, H ), 4.57 (t, 1 H,
1¢
6
This research was supported by the Dirección General de Investig-
ación Científica y Técnica (Grant BQU2002-00120). MBC thanks
MCyT (Ministerio de Ciencia y Tecnología) for a Ramón y Cajal
contract.
J = 3.8 Hz, H ), 4.13 (t, 1 H, J = 9.6 Hz, H ), 3.91 (m, 1 H, H ), 3.69
1
3¢
5¢
(
t, 1 H, J = 9.6 Hz, H ), 3.53 (dd, 1 H, J = 9.6, 3.6 Hz, H ), 2.96 (br
4
¢
2
¢
d, 1 H, J = 10.8 Hz, H ), 2.82 (br d, 1 H, J = 10.7 Hz, H ), 2.67
6
a¢
6b¢
(
br s, 1 H, C OH). Anal. Calcd for C H O N + 3 H O (%): C,
6 61 55 14 3 2
6
6.11; H, 5.50; N, 3.79. Found: C, 66.22; H, 5.30; N, 3.57
2
0
Data of b(1→1) pseudodisaccharide 22: [a]D +14.0 (c 0.2, References
1
CHCl ). H NMR (500 MHz, CDCl ): d = 8.02 (d, 2 H, J = 8.0 Hz,
3
3
(
1) Present address: Departamento de Química Orgánica,
Universidad Autónoma de Madrid, Cantoblanco 28049,
Spain; fax +34(91)4973966; email: Belen.cid@uam.es.
2) (a) Dwek, R. A. Chem Rev. 1996, 96, 683. (b) Varki, A.
Glycobiology 1993, 3, 97. (c) Carbohydrates in Chemistry
and Biology, Vol. 1-4; Ernst, B.; Hart, G. W.; Sinaÿ, P., Eds.;
Wiley-VCH: Weinheim, 2000.
Hortho), 7.93 (d, 2 H, J = 8.0 Hz, Hortho), 7.87 (d, 2 H, J = 8.0 Hz,
Hortho), 7.85 (d, 2 H, J = 8.0 Hz, Hortho), 7.50–7.00 (m, 15 H, 3 Bn
and 12 H, 4 Bz), 6.24 (t, 1 H, J = 9.7 Hz, H ), 6.17 (t, 1 H, J = 9.7
3
(
Hz, H ), 5.87 (dd, 1 H, J = 9.7, 3.1 Hz, H ), 5.80 (dd, 1 H, J = 9.7,
4
2
2
4
2
.9 Hz, H ), 4.87–4.42 (m, 6 H, 3 AB syst.), 4.68 (br s, 1 H, H ),
5
6
.56 (s, 1 H, H ), 4.38 (d, 1 H, J = 8.2 Hz, H ), 3.65–3.57 (m, 4 H,
1
1¢
H , H , H ), 3.34–3.28 (m, 2 H, H , H ), 2.47 (br s, 1 H, C OH).
6
¢
3¢
2¢
4¢
5¢
6
(3) (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
Anal. Calcd for C H O N + 3 H O (%): C, 66.11; H, 5.50; N, 3.7.
6
1
55 14
3
2
(b) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-
Found: C, 66.34; H, 5.58; N, 3.38.
Reid, B. J. Am. Chem. Soc. 1988, 110, 5583.
(
4) (a) Fraser-Reid, B.; Wu, Z. F.; Andrews, C. W.; Skowronski,
E.; Bowen, J. P. J. Am. Chem. Soc. 1991, 113, 1434.
3
2
2
,4,6-Tri-O-benzyl-2-azido-2-deoxy-D-glucopyranosyl-a(1→1)-
,3,4,5-tetra-O-benzyl-D-chiro-inositol (19), 3,4,6-Tri-O-benzyl-
-azido-2-deoxy-D-glucopyranosyl-b(1→1)-2,3,4,5-tetra-O-ben-
(
b) Douglas, N. L.; Ley, S. V.; Lücking, U.; Warriner, S. L.
J. Chem. Soc., Perkin Trans. 1 1998, 51. (c) Zhang, Z.;
Ollman, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.
H. J. Am. Chem. Soc. 1999, 121, 734.
zyl-D-chiro-inositol (23) and Di(3,4,6-tri-O-benzyl-2-azido-2-
deoxy-D-glucopyranosyl)-a,a-(1→1:1→6)-2,3,4,5-tetra-O-ben-
zyl-D-chiro-inositol (26)
These compounds were prepared from 12 (55 mg, 0.088 mmol) and
1
2
(
5) For a review on one-pot glycosylation reactions, see:
Koeller, K. M.; Wong, C. H. Chem. Rev. 2000, 100, 4465.
6) See for example: Ritter, T. K.; Mong, K.-K. T.; Liu, H.;
Nakatani, T.; Wong, C.-H. Angew. Chem. Int. Ed. 2003, 42,
1 (30 mg, 0.055 mmol) as described in the preparation of 18 and
2, adding 0.1 equiv (55 mL of a 0.1 M solution) of TMSOTf at –25
(
°
C, in CH Cl (2 mL) and stirring the reaction mixture for 1 h, yield-
2 2
5221; and references cited therein.
ing after flash chromatography (hexane–EtOAc, 6:1 to 2:1), 33 mg
60%) of 19, 8 mg (14%) of 23, and 10 mg (12%) of the pseudo-
(
7) (a) Huang, X.; Huang, L.; Wang, H.; Ye, X. S. Angew.
Chem. Int. Ed. 2004, 43, 5221. (b) Xia, J.; Alderfer, J. L.;
Locke, R. D.; Piskorz, C. F.; Matta, K. L. J. Org. Chem.
2003, 68, 2752. (c) Xue, J.; Khaja, D.; Locke, R. D.; Matta,
K. L. Synlett 2004, 861.
(
trisaccharide ab 26.
2
0
Data of a(1→1) pseudodisaccharide 19: [a]
CHCl ). H NMR (500 MHz, C D ): d = 7.50–7.10 (m, 35 H, 7 Bn),
5
1
+37.3 (c 1.6,
D
1
3
6
6
.10–4.32 (7 AB syst., 14 H), 4.56 (d, 1 H, J = 3.5 Hz, H ), 4.49 (m,
(8) Sinaÿ, P. Pure Appl. Chem. 1978, 50, 1437.
(9) Boons, G.-J.; Zhu, T. Synlett 1997, 809.
(10) Crich, D.; Dudkin, V. J. Am. Chem. Soc. 2001, 123, 6819.
(11) (a) Khiar, N.; Martín-Lomas, M. In Carbohydrate Mimics.
Concepts and Methods; Chapleur, Y., Ed.; Wiley-VCH:
Weinheim, 1998, 433–462; and references therein.
1
¢
H, H ), 4.31 (br t, 1 H, J = 3.3 Hz, H ), 4.25–4.03 (m, 5 H, H , H ,
5
¢
1
2
3
H , H , H ), 3.99 (br t, 1 H, H ), 3.95 (t, 1 H, J = 9.6 Hz, H ), 3.58
4
5
3¢
6
4¢
(
(
dd, 1 H, J = 10.1, 2.8 Hz, H ), 3.39 (d, 1 H, J = 10.0 Hz H ), 3.22
dd, 1 H, J = 10.1, 3.5 Hz, H ), 2.55 (br s, 1 H, C OH). Anal. Calcd
6¢a 6¢b
2¢
6
for C H O N + H O (%): C, 72.74; H, 6.40; N, 4.17. Found: C,
7
61
63 10
3
2
2.81; H, 6.45; N, 4.50.
(b) Dietrich, H.; Espinosa, J. F.; Chiara, J. L.; Jiménez-
Barbero, J.; León, Y.; Varela-Nieto, I.; Mato, J. M.; Cano, F.
H.; Foces-Foces, C.; Martín-Lomas, M. Chem.–Eur. J. 1999,
2
0
Data of b(1→1) pseudodisaccharide 23: [a]D +2.0 (c 0.6, CHCl3).
1
H NMR (500 MHz, C D ): d = 7.50–7.10 (m, 35 H, 7 Bn), 5.28–
6
6
5, 320. (c) Martín-Lomas, M.; Flores-Mosquera, M.; Chiara,
4
3
.55 (7 AB syst, 14 H), 4.66 (d, 1 H, J = 8.0 Hz, H ), 4.53–4.40 (m,
1¢
J. L. Eur. J. Org. Chem. 2000, 1547. (d) Reichardt, N.-C.;
Martín-Lomas, M. Angew. Chem. Int. Ed. 2003, 40, 4674.
12) (a) Martín-Lomas, M.; Flores-Mosquera, M.; Khiar, N. Eur.
J. Org. Chem. 2000, 1539. (b) Martín-Lomas, M.; Khiar,
N.; Garcia, S.; Koessler, J. L.; Nieto, P. M.; Rademacher, T.
W. Chem.–Eur. J. 2000, 6, 3608. (c) Martín-Lomas, M.;
Nieto, P. M.; Khiar, N.; García, S.; Flores-Mosquera, M.;
Poirot, E.; Angulo, J.; Muñoz, J. L. Tetrahedron: Asymmetry
H, H , H , H or H ), 4.25 (dd, 1 H, J = 9.5, 2.6 Hz, H or H ), 4.14
6
1
4
3
5
2
(dd, 1 H, J = 9.5, 2.6 Hz, H or H ), 4.09 (t, 1 H, J = 9.5 Hz, H or
2
5
3
(
H ), 3.65 (m, 3 H, H , 2 H ), 3.44 (dd, 1 H, J = 9.0, 8.0 Hz, H ),
3
Anal. Calcd for C H O N (%): C, 73.40; H, 6.36; N, 4.21.
Found: C, 73.73; H, 6.69; N, 4.13.
4
4¢
6¢
2¢
.35 (t, 1 H, J = 9.0 Hz H ), 3.28 (m, 1 H, H ), 2.45 (br s, 1 H, OH).
3¢ 5¢
61
63 10
3
1
Data of ab pseudotrisaccharide 26: H NMR (500 MHz, C D ):
d = 7.60–7.10 (m, 50 H, 10 Bn), 5.30–4.40 (10 AB syst., 20 H), 4.86
6
6
2000, 11, 37.
(
d, 1 H, J = 3.5 Hz, H ), 4.73 (d, 1 H, J = 8.7 Hz, H1b¢¢), 4.63 (br t,
1a¢
1
H, H or H ), 4.42 (m, 1 H, H ), 4.43 (m, 2 H, H or H , H or H ),
1 6 5a¢ 4 3 1 6
Synlett 2005, No. 13, 2052–2056 © Thieme Stuttgart · New York