J.-M. Beau, G. Doisneau and C. Papin
1:1) to furnish C-sialoside 2 (1.20 g, 1.78 mmol, 95%) as a white powder.
M.p. 114–1158C; [a]2D6 =À22.7 (c=0.4 in CHCl3); 1H NMR (360 MHz,
ACTHNUTRGNEUNG
CDCl3): d=5.48 (d, 1H; 3J(NH,H-5)=10.1 Hz, NH), 5.39 (ddd, 1H; 3J-
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
(H-8,H-7)=8.3 Hz, 3J (H-8,H-9b)=6.1 Hz, 3J
[2] a) Cell Biology Monograph series: Sialic Acids: Chemistry, Metabo-
lism and Function, Vol. 10 (Ed.: R. Schauer), Springer, Vienna,
3
3
5.27 (dd, 1H; J
ACHTUNGTRENNUNG(H-7,H-8)=8.3 Hz, JACTHUNGTRENNNUG
1H; 3J(H-4,H-3ax)=12.6 Hz, 3J
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
[3] Biology of Sialic Acids (Ed.: A. Rosenberg), Plenum, NewYork,
1995.
4.04–3.97 (m, 2H; H-5, H-6), 3.97–3.88 (m, 2H; NCH2 of cyclohexyl),
3.76 (s, 3H; COOCH3), 3.11–2.95 (m, 2H; NCH2 of cyclohexyl), 2.80
(brs, 1H; OH), 2.43 (dd, 1H; 3J(H-3eq,H-3ax)=12.6 Hz, 3J(H-3eq,H-4)=
4.4 Hz, H-3eq), 2.15, 2.11, 2.03, 2.00 (4s, 12H; 4 OCOCH3), 1.86 (t, 1H;
3J(H-3ax,H-3eq)=3J(H-3ax,H-4)=12.6 Hz, H-3ax), 1.85 (s, 3H; NCOCH3),
1.78–1.54 (m, 4H; 2CH2 of cyclohexyl), 1.44 ppm (s, 9H; C
13C NMR (90 MHz, CDCl3): d=170.9, 170.8, 170.6, 170.2, 169.9, 169.6
(5COCH3, C-1), 154.6 (COOC(CH3)3), 85.5 (C-2), 79.3 (OC(CH3)3), 73.7
[4] R. Schauer in Carbohydrates in Chemistry and Biology, Vol. 3 (Eds.:
B. Ernst, G. W. Hart, P. Sinaꢄ), Wiley-VCH, Weinheim, 2000,
102, 471–490; b) I. Hemeon, A. J. Bennet, Synthesis 2007, 1899–
1926.
ACHTUGNRTNE(NUNG CH3)3);
G
ACHTUNGTRENNUNG
(COH), 73.1 (C-6), 70.1 (C-4), 68.4 (C-8), 67.6 (C-7), 62.6 (C-9), 52.4
(COOCH3), 49.1 (C-5), 39.3, 39.1 (2 NCH2 of cyclohexyl), 32.8 (C-3),
[8] a) O. Blixt, S. Head, T. Mondala, C. Scanlan, M. E. Huflejt, R. Al-
varez, M. C. Bryan, F. Fazio, D. Calarese, J. Stevens, N. Razi, D. J.
Stevens, J. J. Skehel, I. van Die, D. R. Burton, I. A. Wilson, R. Cum-
Price, J. F. Harris, D. M. Lewallen, B. I. Swanson, J. G. Schmidt, S. S.
[9] M. M. Ngundi, N. V. Kulagina, G. P. Anderson, C. R. Taitt, Expert
[10] a) A. Malapelle, Z. Abdallah, G. Doisneau, J.-M. Beau, Angew.
6020; b) A. Malapelle, A. Coslovi, G. Doisneau, J.-M. Beau, Eur. J.
[11] a) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless,
41, 2596–2599; b) C. W. Tornøe, C. Christensen, M. Meldal, J. Org.
Chem. 2002, 67, 3057–3064.
[13] For recent reviews, see: a) V. D. Bock, H. Hiemstra, J. H. van Maar-
[14] For a very recent clustering of S-sialosides to calix[4]arene scaffolds
see: A. Marra, L. Moni, D. Pazzi, A. Corallini, D. Bridib, A. Dondo-
[15] The bromo-azides were prepared by treating an excess of the corre-
sponding dibromoalcanes with sodium azide in DMF at 808C over-
night (46–65% yield).
[16] M. Iwakubo, A. Takami, Y. Okada, T. Kawata, Y. Tagami, M. Sato,
T. Sugiyama, K. Fukushima, S. Taya, M. Amano, K. Kaibuchi, H.
[17] Propargylation of this scaffold will be described in a full paper.
[18] P. Wu, A. K. Feldman, A. K. Nugent, C. J. Hawker, A. Scheel, B.
Voit, J. Pyun, J. M. J. Frꢀchet, K. B. Sharpless, V. V. Fokin, Angew.
[20] a) A. Natarajan, W. Du, C.-Y. Xiong, G. L. DeNardo, S. J. DeNardo,
31.4, 31.0 (2 CH2 of cyclohexyl), 28.3 (OCACHTNUGTRNE(UNG CH3)3), 23.0 (NCOCH3), 20.8,
20.7, 20.6 ppm (4OCOCH3); MS (ESI POS): m/z: 697.1 [M+Na]+;
HRMS: m/z: calcd for C30H46N2O15Na: 697.2790; found: 697.2794.
Hexamer 12 (condition B): A solution of hexa-O-propargylated myo-ino-
sitol (5.0 mg, 0.012 mmol), 3 (49 mg, 0.074 mmol), diisopropylethylamine
(6 mL, 0.034 mmol) and [CuACHTNUGTRNEUGN(PPh3)3Br] (2.3 mg, 0.002 mmol) in THF
(0.2 mL) was stirred at room temperature for 48 h. After evaporation,
the residue was purified by flash chromatography (dichloromethane/
methanol: 8/1 with 0.5% Et3N) to afford 12 (48 mg, 0.011 mmol, 90%).
18
[a] = À0.4 (c=0.47 in CHCl3); 1H NMR (360 MHz, CDCl3): d=8.16,
D
8.14, 8.11, 7.89 (4 s, 6H; CH of triazoles), 5.39 (ddd, 6H; 3J
(H-8,H-7)=
A
ACHTUNGTRENN(UNG H-8,H-9a)=2.6 Hz, H-8), 5.28 (dd, 6H;
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
H-9a), 4.15 (brs, 1H; H-1’), 4.07–3.92 (m, 18H; H-5, H-6 and H-9b), 3.86
(t, 2H; 3J=9.6 Hz, H-4ꢃ and H-6’), 3.78 (s, 18H; COOCH3), 3.37–3.23
(m, 3H; H-1’, H-3ꢃ and H-5’), 2.98–2.66 (m, 18H; OH and NCH2 of cy-
clohexyl), 2.62–2.31 (m, 24H; NCH2 of cyclohexyl and NCH2ACHTUNTRGNEUNG(CH2)2N-tri-
azole), 2.44 (dd, 6H; 3J(H-3eq,H-3ax)=12.7 Hz, J(H-3eq,H-4)=4.8 Hz, H-
3eq), 2.22–2.05 (m, 12H; NCH2CH2CH2N-triazole), 2.14, 2.11, 2.02, 2.00
(4 s, 72H; OCOCH3), 1.92 (t, 6H; 3J(H-3ax,H-3eq)=3J(H-3ax,H-4)=
12.7 Hz, H-3ax), 1.85 (s, 18H; NCOCH3), 1.98–1.87, 1.79–1.59 ppm (m,
24H; CH2 of cyclohexyl); 13C NMR (62,5 MHz, CDCl3): d=171.0, 170.9,
170.7, 170.1, 170.0, 169.8 (5 COCH3 and C-1), 145.1, 145.0, 144.7 (C of tri-
azoles), 124.3, 124.2, 124.1 (CH of triazoles), 85.2 (C-2), 82.7 (C5’), 81.0
(C4’, C6’), 80.2 (C1’, C3’), 73.2 (C-6), 77.2 (COH), 71.7 (C2’), 70.1 (C-4),
68.4 (C-8), 67.7 (C-7), 62.7 (C-9), 54.7 (NCH2ACTHNUTRGEN(UNG CH2)2N-triazole), 52.6
(COOCH3), 49.3 (C-5), 48.8, 48.7, 48.3 (CH2N-triazole and NCH2-cy),
32.8 (C-3), 31.4, 31.0 (CH2 of cyclohexyl), 29.6 23.1 (NCOCH3), 21.3,
20.9, 20.8, 20.7 (4 OCOCH3) ppm; MS (MALDI-TOF): m/z: 4354.81
[M+H]+; HRMS: m/z: calcd for C192H283N30O84
: 4352.8790; found:
4352.8810.
Acknowledgements
The authors gratefully acknowledge the Ministꢁre de la Recherche for a
Ph.D. grant to C.P.
[21] V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew.
Keywords: click reaction · cycloaddition · glycoconjugates ·
samarium · sialic acids
[22] M. Malkoch, K. Schleicher, E. Drockenmuller, C. J. Hawker, T. P.
[23] a) A. Nelson, J. M. Belitsky, S. Vidal, C. S. Joiner, L. G. Baum, J. F.
Rad, S. Behrouz, A. Khalafi-Nezhad, Tetrahedron Lett. 2007, 48,
3445–3449.
56
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 53 – 57