8542
I. Maya et al. / Tetrahedron Letters 44 (2003) 8539–8543
5.05 (m, 6H, H-1B–G), 4.87–4.71 (m, 7H, H-2A–G), 4.58–
References
4.49 (m, 6H, H-6aB–G), 4.31–4.23 (m, 6H, H-6bB–G),
4.18–4.11 (m, 6H, H-5B–G), 3.98–3.94 (m, 1H, H-5A),
3.88–3.82 (m, 1H, H-6aA), 3.76–3.64 (m, 7H, H-4A–G),
3.46–3.41 (m, 1H, H-6bA), 2.14–2.03 (20 s, 60H, 20Ac);
13C NMR (125.7 MHz, CDCl3): l 170.65–170.33, 169.57–
169.32 (CH3CO), 158.20 (CO urea), 96.90–96.67 (C-1A–G),
77.85–76.46 (C-4A–G), 71.24–69.37 (C-2A–G, C-3A–G, C-
5A–G), 62.88–62.36 (C-6B–G), 40.40 (C-6A), 20.80–20.60
(CH3CO) ppm. MALDITOF-MS, m/z 3980 [M+H]+.
17. (a) Cotarca, L.; Eckert, H. Phosgenations - A Handbook;
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21. General procedure for the preparation of sugar ureas: to
a vigorously stirred solution of the hydrohalides 5, 6, 18,
19 (0.6 mmol) in a 1:1 mixture of CH2Cl2 and saturated
aqueous NaHCO3 (12 mL) at 0°C in an ice bath was
added solid triphosgene (0.22 mmol) in a single portion.
After 10 min of stirring, butylamine, p-toludine, or the
corresponding hydrohalides 5, 6, 18, 19 (0.66 mmol) were
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added in a single portion. For the preparation of
D-glu-
cosamine derived ureas 9–14 the coupling with the amines
was performed at rt for 10 min; for the preparation of
glycopyranosyl ureas 22–27 the coupling of the isocyan-
ate with the amines was carried out at 0°C for 20 min.
Conventional work-up and column chromatography
afforded ureas 9–14 and 22–27.
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Jicsinszky, L. Helv. Chim. Acta 1998, 81, 632–645.
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22. For the preparation of 15: the above described procedure
(Ref. 21) was carried out starting from hydrochloride 6
(0.13 mmol). Azide 1 (260 mg, 0.13 mmol) was trans-
formed into amino cyclodextrin derivative 2 as described
above (Ref. 16) which was added to the crude isocyanate
8, and the coupling reaction took place at rt for 15 min.
Conventional work-up and column chromatography
afforded 15 (140 mg, 46%). [h]2D6 +101 (c 1.0, CH2Cl2); IR
1
14. Liu, Q.; Luedtke, N. W.; Tor, Y. Tetrahedron Lett. 2001,
42, 1445–1447.
3295, 1746, 1520, 1456, 1366, 1221 cm−1; H NMR (500
MHz, CDCl3): 5.80 (d, 1H, J1%,2%=8.9 Hz, H-1%), 5.35–
5.21 (m, 8H, H-3A–G, H-3%), 5.14 (d, 1H, J1,2=3.5 Hz,
H-1), 5.15–5.12 (m, 1H, NH), 5.10 (t, 1H, J3%,4%=10.0 Hz,
J4%,5%=10.0 Hz, H-4%), 5.09–5.06 (m, 5H, H-1B–F), 4.98 (d,
1H, J1,2=3.0 Hz, H-1), 4.94–4.91 (m, 1H, NH-CH2), 4.89
(dd, 1H, J1,2=4.5, J2,3=8.5 Hz, H-2), 4.84 (dd, 1H,
15. Jochims, J. C.; Seeliger, A. Tetrahedron 1965, 21, 2611–
2616.
16. A solution of 6A-azido-6A-deoxy-b-
D-cyclodextrin 1 (260
mg, 0.13 mmol) in methanol (10 mL) was hydrogenated
at atmospheric pressure by stirring with 10% Pd(C) cata-
lyst for 2.5 h at rt. After filtration of the mixture through
a Celite pad, the filtrate was concentrated to dryness to
afford the crude amine 2 and divided into two equal
portions. One portion was dissolved in an 1:1 CH2Cl2–
satd aqueous NaHCO3 mixture (12 mL), cooled to 0°C in
an ice bath and treated with solid triphosgene in a single
portion (6.5 mg, 0.022 mmol). After 15 min of vigorous
stirring the other portion of amine 2 was added and the
stirring was maintained at rt for 15 min. Conventional
work-up and column chromatography afforded cyclodex-
trin dimer 4 (127 mg, 49%). [h]2D6 +117 (c 1.1, CH2Cl2); IR
J
J
1,2=4.0, J2,3=9.7 Hz, H-2), 4.81 (dd, 1H, J1,2=3.5,
2,3=10.0 Hz, H-2), 4.80 (dd, 1H, J1,2=3.5, J2,3=9.5 Hz,
H-2), 4.77 (dd, 1H, J1,2=4.1, J2,3=9.5 Hz, H-2), 4.75 (dd,
1H, J1,2=3.6, J2,3=9.5 Hz, H-2), 4.67 (dd, 1H, J1,2=3.5,
J
2,3=10.0 Hz, H-2), 4.65–4.47 (m, 6H, H-6aB–G), 4.33–
4.22 (m, 7H, H-6bB–G, H-6a%), 4.18–4.07 (m, 8H, H-5B–G
,
H-2%, H-6b%), 4.01–3.97 (m, 1H, H-5A), 3.94–3.89 (m, 1H,
H-5%), 3.76–3.59 (m, 8H, H-4A–G, H-6aA), 3.47–3.42 (m,
1H, H-6bA), 2.16–1.99 (24 s, 72H, 24Ac); 13C NMR
(125.7 MHz, CDCl3): l 171.50, 170.94–170.29, 169.55–
169.32 (CH3CO), 157.73 (CO urea), 97.38, 96.96, 96.92,
96.87, 96.76, 96.51, 96.48 (C-1A–G), 92.79 (C-1%), 78.41
(C-4A), 77.25-76.14 (C-4B–G), 72.81 (C-5%), 72.44 (C-3%),
71.46-69.02 (C-2A–G, C-3A–G, C-5A–G), 68.14 (C-4%), 63.05,
1
3300, 1748, 1541, 1433, 1371, 1233, 1042 cm−1; H NMR
(500 MHz, CDCl3): 5.32–5.25 (m, 7H, H-3A–G), 5.17 (d,
1H, J1,2=3.5 Hz, H-1A), 5.14–5.11 (m, 1H, NH), 5.10–