G. Zhang et al. / Bioorg. Med. Chem. 11 (2003) 3273–3278
3277
(C-600), 54.4 (C-200), 37.0 (C-20), 29.6 (CH3), 20.8–20.4
(4C, 4ꢂCH3CO); ESI-TOF MS: 702.1284 (M++1)
724.1027 (M++Na).
(1:1) to elute the desired products. The product was
purified again on the short C18 column (H2O) to give
the pure target compound (14–19).
300,400,600-Tri-O-acetyl-200-deoxy-200-phthalimido-ꢀ-D-ga-
lactopyranosyl (1!5)-20, 30-di-O-acetyl-uridine 11.
200-Deoxy-200-amino-ꢀ-D-glucopyranosyl (1!5)-uridine 14.
18
Yield: 77%; ½aꢁD +4.4 (c 0.020, H2O); H NMR (D2O)
1
18
Yield: 90%; ½aꢁD À25.6 (c 0.027, CHCl3); 1H NMR
d: 7.65 (d, 1H, J5,6=7.5 Hz, H-6), 5.72 (m, 2H, H-10, H-
0
5), 4.69 (1H, H-100), 4.23 (t, 1H, J1 ,2 =4.2 Hz, H-2 ),
0
0
(CDCl3) d: 9.08 (s, 1H, HN), 7.83, 7.75 (2m, 4H, Ph),
7.72 (d, 1H, J5,6=8.5 Hz, H-6), 6.14 (d, 1H, J1 ,2 =6.0
4.12 (m, 3H, H-40, H-30, H-5a0), 3.82 (m, 2H, H-5b0, H-
00
0
00
Hz, H-10), 5.91–5.88 (m, 2H, H-5, H-3 ), 5.53 (m, 1H,
300), 3.57 (m, 2H, H-6a00, H-400), 3.35 (m, 2H, H-500, H-
6b00), 2.94 (t, 1H, J1 ,2 =8.7 Hz, H-2 ); 13C NMR (D2O)
00
00
H-400), 5.31 (d, 1H, J1 ,2 =8.0 Hz, H-1 ), 5.08 (m, 1H,
00 00
00 00
H-20), 5.00 (t, 1H, H-30), 4.51 (dd, 1H, J2 ,3 =11.50 Hz,
d: 168.9 (C-4), 154.3 (C-6), 145.0 (C-2), 105.0 (C-5),
101.4 (C-100), 93.0 (C-10), 85.2 (C-40), 79.0 (C-30), 76.0
(C-500), 74.7 (C-300), 72.6 (C-20), 72.3 (C-400), 71.9 (C-50),
63.2 (C-600), 58.6 (C-200); HRFAB+ (C15H24O10N3+H+)
calcd 406.1462, found 406.1494.
00 00
H-200), 4.25–4.12 (m, 5H, H-6a00, H-40, H-5a0, H-6b00, H-
500), 3.69 (m, 1H, H-5b0), 1.86, 1.98, 1.99, 2.08, 2.25 (5s,
15H, 5ꢂOAc); 13C NMR (CDCl3) d: 170.4–162.8 (8C,
MeCO, PhCO), 150.4 (C-4), 139.8 (C-6), 134.4, 123.7 (2C,
Ph), 131.8 (C-2), 103.2 (C-5), 98.0 (C-100), 86.0 (C-10), 81.4
(C-40), 73.2 (C-30), 71.0 (C-500), 70.8 (C-300), 67.7 (C-20),
67.4 (C-400), 66.6 (C-50), 61.2 (C-600), 51.1 (C-200), 20.8–20.2
(5C, 5ꢂCH3CO); ESI-TOF MS: 746. 2148 (M++1).
200-Deoxy-200-amino-ꢀ-D-glucopyranosyl (1!5)-cytidine 15.
18
Yield: 83%; ½aꢁD +10.1 (c 0.018, H2O); 1H NMR
(D2O) d: 7.69 (d, 1H, J5,6=7.5 0Hz, H-6), 5.89 (d, 1H, H-
0
0
00 00
5), 5.73 (d, J1 ,2 =3.9 Hz, H-1 ), 4.50 (d,1H, J1 ,2 =8.4
300,400,600-Tri-O-acetyl-200-deoxy-200-phthalimido-ꢀ-D-ga-
Hz, H-100), 4.21 (t, 1H, J1 ,2 =4.2 Hz, H-2 ), 4.19–4.13
(m, 3H, H-40, H-30, H-5a0), 3.80 (m, 2H, H-6a00,H-300),
3.40 (m, 1H, H-5b0), 3.43–3.26 (m, 3H, H-400, H-500, H-
6b00), 2.74 (1H, H-200); 13C NMR (D2O) d: 168.9 (C-4),
160.1 (C-6), 145.0 (C-2), 101.5 (C-5), 98.9 (C-100), 94.1
(C-10), 84.8 (C-40), 79.0 (C-30), 76.2 (C-500), 74.8 (C-300),
72.6 (C-20), 72.2 (C-400), 71.9 (C-50), 63.2 (C-600), 58.6 (C-
200); HRFAB+ (C15H25O9N4+H+) calcd 405.1622,
found 405.1614.
0
0
0
lactopyranosyl
(1!5)-20,30-di-O-acetyl-N4-acetyl-cyti-
18
1
dine 12. Yield: 65%; ½aꢁD À10.3 (c 0.017, CHCl3); H
NMR (CDCl3) d: 9.97 (s, 1H, HNAc), 8.17 (d, 1H,
J5,6=7.0 Hz, H-6), 7.85–7.71 (2m, 4H, Ph), 7.58 (d, 1H,
0
00
0
0
H-5), 6.24 (d, 1H, J1 ,2 =4.0 Hz, H-1 ), 5.68 (m, H-3 ),
5.47-5.28 (m, 4H, H-100;, H-400, H-20, H-30), 5.07 (m, 1H,
H-200), 4.70 (m, 1H, H-6a00), 4.49–4.15 (m, 4H, H-40, H-5a0,
H-6b00, H-500), 3.65 (m, 1H, H-5b0), 2.00, 2.06, 2.08, 2.09,
2.25, 2.30 (6s, 18H, 5ꢂOAc, 1ꢂNHAc ); 13C NMR
(CDCl3) d: 170.5–167.4 (6C, CO), 131.6 (C-2), 134.2,
123.7 (Ph), 104.4 (C-5), 97.3 (C-100), 88.0 (C-10), 81.2 (C-
40), 78.4 (C-30), 74.1 (C-500), 72.6 (C-300), 70.1 (C-20), 68.7
(C-400), 67.1 (C-50), 62.2 (C-600), 61.2 (C-200), 24.9–20.3 (6C,
6ꢂCH3CO); ESI-TOF MS: 787.2454 (M++1).
200-Deoxy-200-amino-ꢀ-D-glucopyranosyl (1!5)-thymidine
18
1
16. Yield: 85%; ½aꢁD +0.5 (c 0.008, H2O); H NMR
0
0
0
(D2O) d: 7.44 (s, 1H, H-6), 6.17 (t, J1 ,2 =6.7 Hz, H-1 ),
4.68 (d, 1H, H-100), 4.40 (dd, 1H, H-30), 4.09–4.05 (m,
2H, H-5a0, H-40), 3.84–3.79 (m, 2H, H-200, H-6a00), 3.64–
3.57 (m, 2H, H-400, H-5b0), 3.39–3.33 (m, 2H, H-500, H-
300,400,600-Tri-O-acetyl-200-deoxy-200-phthalimido-ꢀ-D-ga-
6b00), 2.95 (dd, 1H, J2 ,3 =8.5 Hz, J3 ,4 =10.5 Hz, H-
300), 2.34–2.25 (m, 2H, H-20), 1.79 (s, 3H, CH3); 13C
NMR (D2O) d: 166.8 (C-4), 152.0 (C-6), 138.1 (C-2),
111.8 (C-5), 99.1 (C-100), 85.9 (C-10), 85.0 (C-40), 76.7 (C-
30), 72.4 (C-500), 71.0 (C-50), 70.2 (C-300), 70.0 (C-600), 60.9
(C-600), 56.2 (C-200), 38.3 (C-20), 26.3 (CH3); HRFAB+
(C16H26O9N3+H+) calcd 404.1669, found 404.1680.
00 00
00 00
lactopyranosyl (1!5)-30-O-acetyl-thymidine 13. Yield:
18
87%; ½aꢁD À37.8 (c 0.046, CHCl3); 1H NMR (CDCl3) d:
8.49 (s,1H, HN), 7.88–7.76 (2m, 4H, Ph), 7.62 (s, 1H, H-
6), 6.34 (m, 1H, H-10), 5.94 (dd, 1H,00 J2 ,3 =11 Hz,
00 00
00
00 00
J3 ,4 =3.0 Hz, H-3 ), 5.55 (m, 1H, H-4 ), 5.29 (d, 1H,
00 00
00
0
J1 ,2 =8.5 Hz, H-1 ), 4.74 (m, 1H, H-3 ), 4.53 (dd, 1H,
H-200), 4.27–4.14 (m, 4H, H-6a00, H-5a0, H-6b00, H-500),
4.08 (m, 1H, H-40), 3.67 (m, 1H, H-5b0), 2.17–1.95 (5s,
15H, 4ꢂOAc, CH3), 1.88 (m, 2H, H-20); 13C
NMR(CDCl3) d: 170.0, 170.1, 170.0, 169.6 (4C, CO),
168.0, 163.8 (PhCO), 150.6 (C-4), 135.6 (C-6), 134.4,
123.7 (2C, Ph), 130.9 (C-2), 111.5 (C-5), 98.5 (C-100),
84.4 (C-10), 83.0 (C-40), 75.0 (C-30), 71.2 (C-500), 69.7 (C-
50), 67.4 (C-300), 66.6 (C-400), 61.2 (C-600), 51.3 (C-200),
37.0 (C-20), 20.7–20.4 (4C, 4ꢂCH3CO); 12.6 (CH3);
ESI-TOF MS: 702.2216 (M++1), 724.2122 (M++Na).
200-Deoxy-200-amino-ꢀ-D-galactopyranosyl (1!5)-uridine
18
17. Yield: 83%; ½aꢁD +10.4 (c 0.020, H2O); H NMR
1
(D2O) d: 7.78 (d, 1H, J5,6=8.1 Hz, H-6), 5.72 (m, 2H,
00
H-10, H-5), 4.28 (d,1H, J1 ,2 =8.1 Hz, H-1 ), 4.21 (m,
00 00
4H, H-20, H-40, H-30, H-5a0), 3.76–3.43 (m, 6H, H-6a00,
H-400, H-300, H-6b00, H-500, H-5b0), 2.84-2.73 (m, 1H, H-
200); 13C NMR (D2O) d: 169.5 (C-4), 154.7 (C-2), 144.8
(C-6), 105.7 (C-5), 104.9 (C-100), 92.5 (C-10), 85.5 (C-40),
78.1 (C-30), 76.4 (C-500), 74.9 (C-300), 72.2 (C-20), 71.2 (C-
400), 70.6 (C-50), 64.0 (C-600), 55.7 (C-200); HRFAB+
(C15H24O10N3+H+) calcd 406.1462, found 406.1478.
General procedure for deprotection
Compound (8–13) (50 mg) was added to 10 mL of 25–
30% methylamine in absolute ethanol with stirring at
room temperature. After 8 h, the clear solution obtained
was refluxed for 6 h. The mixture was evaporated under
reduced pressure. The residue was purified by chroma-
tography on silica gel using dichloromethane/methanol
200-Deoxy-200-amino-ꢀ-D-galactopyranosyl (1!5)-cytidine
18
18. Yield: 83%; ½aꢁD +5.7 (c 0.021, H2O); H NMR
1
(D2O) d: 7.63 (d, 1H, J5,6=7.5 Hz, H-6), 5.89 (d, 1H, H-
0
00
0
0
5), 5.69 (d, 1H, J1 ,2 =3.6 Hz, H-1 ), 4.66 (1H, H-1 ),
4.21 (t, 1H, H-20), 4.11 (m, 3H, H-40, H-30, H-5a0), 3.77
(m, 2H, H-6a00, H-300), 3.61 (m, 2H, H-5b0, H-400), 3.32