F. M. Ibatullin, S. I. Selivanov / Tetrahedron Letters 50 (2009) 6351–6354
6353
13. (a) Garg, H. G.; Jeanloz, R. W. Carbohydr. Res. 1972, 23, 437–439; (b) Garg, H. G.;
Jeanloz, R. W. Carbohydr. Res. 1979, 70, 47–58; (c) Tamura, M.; Nishizaki, H.;
Okai, H.; Oka, S. Peptide Chem. 1980, 15–20.
14. (a) Huang, X.; Luo, X.; Roupioz, Y.; Keillor, J. W. J. Org. Chem. 1997, 62, 8821–
8825; (b) Cooper, W. J.; Waters, M. L. Org. Lett. 2005, 7, 3825–3828.
15. (a) Ibatullin, F. M.; Shabalin, K. A. Synth. Commun. 2000, 30, 2818–2823; (b)
Ibatullin, F. M.; Shabalin, K. A. Carbohydr. Lett. 2000, 3, 427–429.
The spectrum (rm + 3%
mixture with 97% ee, was measured after the addition of about
3% per-O-acetylated glucosyl N-Fmoc-D-asparagine to the reaction
mixture.
In summary, a simple and efficient one-step method for the
preparation of N-glycosyl asparagine derivatives, based on the
reaction of glycosyl amines with N-Fmoc-aspartic anhydride in
DMSO, has been developed. The starting anhydride can easily be
prepared in two steps from aspartic acid. The method provides
an efficient and simple route for the preparation of various N-gly-
cosyl asparagine derivatives, the building blocks for liquid- and
solid-phase syntheses of glycopeptides.
D), corresponding to the reaction
16. The NMR data are presented using the convention followed in Carbohydrate
Research (see instructions to Authors).N-Fmoc-L
-aspartic anhydride (1). 1H
NMR (DMSO-d6, 500 MHz): d (ppm) 8.21 (d, 1H, J = 7.6 Hz, NH-Asp), 7.88 (d,
2H, J = 7.4 Hz, HAr-Fmoc), 7.68 (d, 2H, J = 7.4 Hz, HAr-Fmoc), 7.42 (t, 2H, J = 7.4,
Hz, HAr-Fmoc), 7.34 (t, 2H, J = 7.4 Hz, HAr-Fmoc), 4.70 (dq, 1H, J,1 = 10.1 Hz,
J,2 = 6.2 Hz, a-H-Asp), 4.44 (dd, 1H, J2a,2b = 10.4 Hz, a-CH2-Fmoc), 4.41 (dd, 1H,
b-CH2-Fmoc), 4.26 (dd, 1H, Ja,9 = 6.7 Hz, Jb,9 = 6.3 Hz, H-9 Fmoc), 3.27 (dd, 1H,
J1,2 = 18.4 Hz, b1-H-Asp), 2.89 (dd, 1H, b2-H-Asp). 13C NMR (DMSO-d6,
125 MHz): d (ppm) 172.2, 169.9 (CO-Asp), 156.0 (CO-Fmoc), 143.7, 143.6,
140.9, 127.8, 127.2, 127.1, 125.2, 125.1, 120.3, 120.2 (Ar-Fmoc), 66.2 (CH2-
Fmoc), 50.5 (CH-Asp), 46.7 (CH-Fmoc), 34.8 (CH2-Asp).2,3,4,6-tetra-O-acetyl-
Acknowledgments
N-[N-Fmoc-L-aspart-4-oyl]-b-D
-glucopyranosylamine (2). Yield 82%. 1H NMR
(DMSO-d6, 500 MHz): d (ppm) 8.75 d 1H J1NH = 9.4 Hz, NH-Glc), 7.88 (d, 2H,
J = 7.5 Hz, HAr-Fmoc), 7.70 (dd, 2H, J = 7.4 Hz, J = 7.4 Hz, HAr-Fmoc), 7.57 (d, 1H,
The authors thank Dr. K. A. Shabalin for help with recording
some of the NMR spectra, and Dr. J. V. Jänis and Dr. G. Sundqvist
for mass spectrometry, and Professor V. Bulone and Dr. C. Hooij-
maijers for assistance in the preparation of the manuscript.
J = 8.4 Hz, NH-Asn), 7.40 (t, 2H, J = 7.5 Hz, HAr-Fmoc), 7.32 (t, 2H, J = 7.4 Hz, HAr
-
Fmoc), 5.41 (dd, 1H, J1,2 = 9.3 Hz, H-1), 5.33 (dd, 1H, J3,4 = 9.6 Hz, H-3), 4.91 (dd,
1H, J4,5 = 9.7 Hz, H-4), 4.82 (dd, 1H, J2,3 = 9.4 Hz, H-2), 4.38 (dt, 1H, J,1 = 6.1 Hz,
J,2 = 7.4 Hz, a-CH-Asn), 4.27 (d, 2H, a,b-CH2-Fmoc), 4.20 (dd, 1H, J = 6.6 Hz, H-9
Fmoc), 4.16 (dd, 1H, J6a,6b = 12.3 Hz, H-6a), 4.09 (dq, 1H, J5,6a = 4.4 Hz, J5,6b = 2.2,
H-5), 3.97 (dd, 1H, H-6b), 2.64 (dd, 1H, J1,2 = 15.8 Hz, b1-H-Asn), 2.52 (m, 1H,
b2-H-Asn), 1.99, 1.98, 1.92, 1.89 (4s, each 3H, 4 ꢀ CH3CO). 13C NMR (DMSO-d6,
125 MHz): d (ppm) 172.81 (COOH), 169.90 (CO-NH), 169.63, 169.39, 169.20,
169.00 (CO-Ac), 155.73 (CO-Fmoc), 143.70, 143.64, 140.59, 127.53, 126.98,
125.16, 120.00 (Ar-Fmoc), 76.70 (C-1), 72.77 (C-3), 71.99 (C-5), 70.45 (C-2),
67.69 (C-4), 65.60 (CH2-Fmoc), 61.62 (C-6), 50.12 (CH-Asn), 46.49 (CH-Fmoc),
20.41, 20.27, 20.21, 20.18 (CH3-Ac). ESI FT-ICR HRMS (m/z): 707.2066
(707.2064 calculated for C33H36N2NaO14 [M+Na]+).2,3,4,6-tetra-O-acetyl-N-
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
[N-Fmoc-D-aspart-4-oyl]-b-D
-glucopyranosylamine (3). Yield 51%. 1H NMR
(DMSO-d6, 500 MHz): d (ppm) 8.83 d 1H J1NH = 9.4 Hz, NH-Glc), 7.89 (d, 2H,
J = 7.5 Hz, HAr-Fmoc), 7.70 (dd, 2H, J = 7.4 Hz, HAr-Fmoc), 7.59 (d, 1H, J = 7.9 Hz,
NH-Asn), 7.41 (dt, 2H, J = 7.5 Hz, HAr-Fmoc), 7.33 (2dt, 2H, J = 7.5 Hz, J = 7.4 Hz,
HAr-Fmoc), 5.41 (dd, 1H, J1,2 = 9.4 Hz, H-1), 5.34 (dd, 1H, J3,4 = 9.6 Hz, H-3), 4.88
(dd, 1H, J4,5 = 9.7 Hz, H-4), 4.81 (dd, 1H, J2,3 = 9.4 Hz, H-2), 4.36 (dt, 1H,
J,1 = 6.2 Hz, J,2 = 7.3 Hz, a-CH-Asn), 4.29 (d, 2H, a,b-CH2-Fmoc), 4.22 (m, 1H, H-9
Fmoc), 4.13 (dd, 1H, J6a,6b = 12.3 Hz, H-6a), 4.08 (ddd, 1H, J5,6a = 4.4 Hz,
J5,6b = 2.2, H-5), 3.95 (dd, 1H, H-6b), 2.64 (dd, 1H, J1,2 = 15.7 Hz, b1-H-Asn),
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3578.
2.44 (dd, 1H, b2-H-Asn), 1.983, 1.978, 1.93, 1.92 (4s, each 3H, 4 ꢀ CH3CO).13
C
NMR (DMSO-d6, 125 MHz): d (ppm) 172.79 (COOH), 169.89 (CO-NH), 169.64,
169.40, 169.21, 169.08 (CO-Ac), 155.71 (CO-Fmoc), 143.69, 140.60, 127.53,
127.00, 125.15, 120.02 (Ar-Fmoc), 76.69 (C-1), 72.75 (C-3), 71.99 (C-5), 70.53
(C-2), 67.70 (C-4), 65.58 (CH2-Fmoc), 61.61 (C-6), 50.10 (CH-Asn), 46.1 (CH-
Fmoc), 20.41, 20.28, 20.22, 20.20 (CH3-Ac). ESI FT-ICR HRMS (m/z): 707.2066
(707.2064 calculated for C33H36N2NaO14 [M+Na]+).2-acetamido-2-deoxy-3,4,6-
tri-O-acetyl-N-[N-Fmoc-L-aspart-4-oyl]-b-D-glucopyranosylamine (4). Yield
85%. 1H NMR (DMSO-d6, 500 MHz): d (ppm) 8.61 d 1H J1NH = 9.0 Hz, NH-Glc),
7.91 (d, 1H, J = 9.0 Hz, NH-Ac), 7.88 (d, 2H, J = 7.6 Hz, HAr-Fmoc), 7.70 (dd, 2H,
J = 7.5 Hz, HAr-Fmoc), 7.52 (d, 1H, J = 8.6 Hz, a-NH-Asn), 7.41 (t, 2H, J = 7.5 Hz,
HAr-Fmoc), 7.32 (t, 2H, J = 7.5 Hz, HAr-Fmoc), 5.19 (dd, 1H, J1,2 = 9.5 Hz, H-1),
5.11 (dd, 1H, J3,4 = 9.8 Hz, H-3), 4.83 (dd, 1H, J4,5 = 9.8 Hz, H-4), 4.40 (dt, 1H,
J,1 = 5.5 Hz, J,2 = 8.3 Hz,
a-CH-Asn), 4.36 (dd, 1H, Ja,b = 10.3 Hz, Ja,9 = 7.0 Hz, a-
CH2 Fmoc), 4.25 (dd, 1H, Jb,9 = 6.9 Hz, b-CH2 Fmoc), 4.21 (m, 1H, H-9 Fmoc),
4.19 (dd, 1H, J6a,6b = 12.4 Hz, H-6a), 3.95 (m, 1H, H-6b), 3.88 (dd, 1H,
J2,3 = 9.8 Hz, J2,NH = 9.8 Hz, H-2), 3.82 (dq, 1H, J5,6a = 4.1 Hz, J5,6b = 1.9 Hz, H-5),
2.67 (dd, 1H, Ja,b = 16.1 Hz, b1-H-Asn), 2.51 (m, 1H, b2-H-Asn), 1.99, 1.96, 1.91
(3s, each 3H, 3 ꢀ CH3CO), 1.73 (s, 3H, CH3CON). 13C NMR (DMSO-d6, 125 MHz):
d (ppm) 172.85 (COOH), 169.92 (CO-NH Asn), 169.70 (CO-AcNH), 169.39,
169.37, 169.20 (CO-Ac), 155.72 (CO-Fmoc), 143.68, 140.59, 127.53, 126.98,
125.15, 120.00 (Ar-Fmoc), 77.98 (C-1), 73.26 (C-3), 72.18 (C-5), 68.28 (C-4),
65.60 (CH2-Fmoc), 61.73 (C-6), 52.01 (C-2), 49.91 (CH-Asn), 46.50 (CH-Fmoc),
36.77 (CH3-NAc), 20.42, 20.30, 20.27 (CH3-Ac). ESI FT-ICR HRMS (m/z):
706.2225 (706.2224 calculated for C33H37N3NaO13 [M+Na]+).4-O-(2,3,4,6-
tetra-O-acetyl-b-
D-glucopyranosyl)-2,3,6-tri-O-acetyl-N-[N-Fmoc-L-aspart-4-
oyl]-b-
D
-glucopyranosylamine (5). Yield 73%. 1H NMR (CDCl3, 500 MHz): d
(ppm) 7.75 (d, 2H, J = 7.5 Hz, HAr-Fmoc), 7.58 (dd, 2H, J = 7.5 Hz, HAr-Fmoc),
7.39 (t, 2H, J = 7.4 Hz, HAr-Fmoc), 7.30 (t, 2H, J = 7.4 Hz, HAr-Fmoc), 6.68 d 1H
J1NH = 9.0 Hz, NH-Glc), 6.19 (d, 1H, J = 8.1 Hz, NH-Asn), 5.30 (dd, 1H,
0
0
J3,4 = 8.2 Hz, H-3), 5.23 (dd, 1H, J1,2 = 9.4 Hz, H-1), 5.14 (dd, 1H, J3 ,4 = 9.3 Hz,
H-30), 5.07 (dd, 1H, J4 ,5 = 9.7 Hz, H-40), 4.92 (dd, 1H, J2 ,3 = 9.0 Hz, H-20) 4.84
(dd, 1H, J2,3 = 9.5 Hz, H-2), 4.57 (m, 1H, J,1 = 4.6 Hz, J,2 = 5.0 Hz, H- -Asn), 4.50
0
0
0
0
a
0
0
(d, 1H, J1 ,2 = 8.0 Hz, H-1), 4.46 (m, 1H, J6a,6b = 11.9 Hz, H-6a), 4.39 (m, 1H,
Ja,b = 10.8 Hz, a-CH2-Fmoc), 4.36 (m, 1H, J6 a,6 b = 12.7 Hz, H-60a), 4.34 (m, 1H, b-
CH2-Fmoc), 4.21 (dd, 1H, J = 7.3 Hz, H-9-Fmoc), 4.14 (m, 1H, H-6b), 4.03 (dd,
0
0
1H, H-60b), 3.75 (m, 2H, H-4, H-5), 3.65 (dq, 1H, J5 ,6 a = 3.5 Hz, J5 ,6 b = 2.4 Hz, H-
50), 2.89 (dd, 1H, J1,2 = 16.2 Hz, H-b1-Asn), 2.75 (dd, 1H, H-b2-Asn), 2.09, 2.08,
2.024, 2.02, 2.01, 1.98 (6s, 21H, 7 ꢀ CH3CO). 13C NMR (CDCl3, 125 MHz): d
(ppm) 172.61 (COOH), 171.59, 171.47, 170.51, 170.36, 170.24, 169.65, 169.30,
169.06 (CO-NH, CO-Ac), 156.64 (CO-Fmoc), 143.69, 143.61, 141.25, 127.76,
127.10, 125.12, 120.00 (Ar-Fmoc), 100.63 (C-10), 77.89 (C-1), 76.09, 74.72,
72.87, 72.15, 71.93, 71.52, 70.75, 67.79 (C-2, C-20, C-3, C-30, C-4, C-40, C-5, C-50),
0
0
0
0
11. Tennant-Eyles, R. J.; Fairbanks, A. J. Tetrahedron: Asymmetry 1999, 10, 391–401.
12. (a) Bergmann, M.; Zervas, L. Ber. Deutsch. Chem. Ges. 1932, 65, 1192–1201; (b)
Bergmann, M.; Zervas, L.; Salzmann, L.; Schleich, H. Z. Physiol. Chem. 1934, 224,
17–26; (c) Le Quesne, W. J.; Young, G. T. J. Chem. Soc. 1952, 24–28.