F. Diederich et al.
FULL PAPER
6.6 Hz, 1H), 6.03 (d, J 6.6 Hz, 1H), 5.68 ± 5.67 (m, 1H), 5.57 (t, J 5.4 Hz,
1H), 4.41 ± 4.40 (m, 1H), 4.37 ± 4.35 (d, J 7.4 Hz, 2H), 4.22 (t, J 7.4 Hz,
1H), 3.85 (d, J 9.3 Hz, 1H), 3.73 (d, J 5.2 Hz, 2H), 3.62 ± 3.61 (m, 1H),
3.50 ± 3.48 (m, 2H), 2.17 (s, 3H), 2.07 (s, 3H); 13C NMR (125 MHz, CDCl3):
d 167.63, 167.47, 162.26, 154.36, 150.68, 149.69, 147.34, 141.76, 141.69,
138.87, 131.15, 130.42, 126.49, 125.50, 125.28, 124.65, 124.55, 122.81, 117.57,
82.65, 80.08, 71.54, 69.42, 68.40, 67.96, 64.62, 44.69, 38.53, 18.22, 17.96; MS
132.61, 128.44, 127.89, 126.78, 122.53, 115.39, 113.88, 111.31, 85.45, 82.34,
73.15, 71.35, 69.81, 69.74, 39.09, 20.19, 19.87; HR-MS (FAB): calcd for
C30H30N7O12 [MH] : 680.1952; found: 680.1952.
(2S,3R,4R,5R)-2-[4-(Benzoylamino)-2-oxo-1,2-dihydropyrimidin-1-yl]-5-
({2-[(2,3-dihydroxy-5-nitrobenzoyl)amino]ethoxy}methyl)tetrahydrofur-
an-3,4-diyl diacetate (22): Starting from 9 (100 mg, 0.14 mmol) and 11
(41 mg, 0.14 mmol), the procedure described for 21 afforded 22 (46 mg,
(FAB): m/z (%): 743 (22) [MNa] , 721 (100) [MH] ; HR-MS (FAB):
20
49%) as an orange powder. M.p. 1468C; [a] 40.0 (c 1.0, THF); IR
D
calcd for C38H37N6O9 [MH] : 721.2622; found: 721.2625.
(KBr): nÄ 3422, 2978, 2933, 1750, 1700, 1656, 1628, 1561, 1483, 1372, 1311,
1250, 1128, 1072, 806, 783, 706 cm 1; 1H NMR (500 MHz, CD3OD): d 8.50
(d, J 3.0 Hz, 1H), 8.39 (d, J 7.6 Hz, 1H), 8.00 ± 7.90 (m, 2H), 7.67 ± 7.56
(m, 3H), 7.51 (d, J 7.6 Hz, 1H), 7.46 (d, J 3.0 Hz, 1H), 6.24 (d, J
5.2 Hz, 1H), 5.70 ± 5.65 (m, 1H), 5.62 ± 5.58 (m, 1H), 4.50 ± 4.45 (m, 1H),
4.05 ± 3.65 (m, 6H), 2.15 (s, 3H), 2.10 (s, 3H); 13C NMR (125 MHz,
CD3OD): d 171.47, 171.14, 170.04, 168.81, 164.99, 157.96, 150.13, 146.07,
134.67, 134.00, 129.87, 129.74, 129.22, 120.53, 115.91, 108.17, 99.12, 96.76,
89.65, 83.92, 76.00, 72.75, 71.43, 70.73, 40.13, 20.53, 20.34; MS (FAB): m/z
(2S,3R,4R,5R)-2-[4-(Benzoylamino)-2-oxo-1,2-dihydropyrimidin-1-yl]-5-
[(2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethoxy)methyl]tetrahy-
drofuran-3,4-diyl diacetate (9): BSA (0.16 mL, 0.66 mmol) was added at
508C to a stirred suspension of 4-N-benzoylcytosine (72 mg, 0.33 mmol) in
MeCN (2 mL). After 10 min, a colorless solution formed to which 7
(150 mg, 0.28 mmol) in MeCN (1 mL) and TMSOTf (0.25 mL, 1.38 mmol)
were added under Ar. The mixture was stirred at 558C for 20 min, then
quenched with a saturated aqueous solution of NaHCO3 (20 mL) and
EtOAc (20 mL), and extracted with EtOAc (3 Â 50 mL). The combined
organic layers were evaporated in vacuo, and FC (SiO2 H, CH2Cl2/MeOH
98.5:1.5) afforded 9 as a white powder (0.152 g, 79%). M.p. 184 ± 1858C;
[a]2D0 29.0 (c 1.0, CHCl3); IR (KBr): nÄ 3370, 3067, 2956, 2878, 1746,
(%): 678.1 (24) [MNa] , 656.1 (100) [MH] ; HR-MS (FAB): calcd for
C29H30N5O13 [MH] : 656.1840; found: 656.1843.
(2S,3R,4R,5R)-2-[4-(Benzoylamino)-6-oxo-1,6-dihydropyrimidin-1-yl]-5-
({2-[(2,3-dihydroxy-5-nitrobenzoyl)amino]ethoxy}methyl)tetrahydrofur-
an-3,4-diyl diacetate (23): Starting from 10 (100 mg, 0.14 mmol) and 11
(41 mg, 0.14 mmol), the procedure described for 21 afforded 23 (53 mg,
56%) as an orange powder. M.p. 1478C; [a]2D0 25.0 (c 1.0, THF); IR
(KBr): nÄ 3400, 2967, 2867, 1750, 1690, 1558, 1509, 1444, 1372, 1328, 1248,
1695, 1670, 1615, 1555, 1525, 1488, 1374, 1309, 1248, 1139, 1090, 790, 738,
1
706 cm
;
1H NMR (500 MHz, CDCl3): d 8.65 (s, 1H), 8.21 ± 8.18 (m,
1H), 7.78 (d, J 5.7 Hz, 2H), 7.67 (d, J 7.5 Hz, 2H), 7.65 ± 7.55 (m, 4H),
7.48 ± 7.44 (m, 2H), 7.36 ± 7.32 (m, 2H), 7.28 ± 7.22 (m, 2H), 6.37 (d, J
5.4 Hz, 1H), 5.55 ± 5.48 (m, 3H), 4.41 (d, J 7.3 Hz, 2H), 4.33 (m, 1H), 4.23
(t, J 7.3 Hz, 1H), 3.89 (d, J 10.4 Hz, 1H), 3.77 ± 3.75 (m, 1H), 3.68 (d,
J 10.4 Hz, 1H), 3.62 ± 3.60 (m, 1H), 3.50 ± 3.45 (m, 2H), 2.12 (s, 3H), 2.11
(s, 3H); 13C NMR (125 MHz, CDCl3): d 169.88, 166.04, 162.35, 156.58,
144.34, 144.01, 143.98, 141.21, 133.11, 128.91, 127.56, 126.94, 125.22, 125.19,
119.84, 87.44, 81.84, 74.22, 70.91, 70.71, 69.71, 66.94, 47.18, 40.97, 20.64, 20.51
1
1133, 1074, 844, 806, 702 cm 1; H NMR (500 MHz, CD3OD): d 8.75 (d,
J 0.7 Hz, 1H), 8.50 (d, J 3.0 Hz, 1H), 8.00 ± 7.90 (m, 2H), 7.70 ± 7.50 (m,
3H), 7.48 (d, J 3.0 Hz, 1H), 7.29 (d, J 0.7 Hz, 1H), 6.30 (d, J 5.1 Hz,
1H), 5.76 ± 5.70 (m, 1H), 5.68 ± 5.62 (m, 1H), 4.48 ± 4.42 (m, 1H), 4.05 ± 3.80
(m, 6H), 2.10 (s, 3H), 2.06 (s, 3H); 13C NMR (125 MHz, CD3OD): d
171.47, 171.14, 170.14, 168.83, 164.47, 157.57, 150.26, 149.67, 149.62, 134.97,
133.65, 129.77, 128.90, 120.67, 116.09, 107.50, 98.42, 88.02, 83.85, 76.12, 72.52,
71.11, 70.64, 40.21, 20.52, 20.30 (1 peak missing); HR-MS (FAB): calcd for
(3 peaks missing); MS (FAB): m/z (%): 697.2 (100) [MH] ; HR-MS (FAB):
calcd for C37H37N4O10 [MH] : 697.2509; found: 697.2516; C37H36N4O10
(696.72): calcd: C 63.79, H 5.21, N 7.76; found: C 63.85, H 5.39, N 7.97.
C29H29N5NaO13 [MNa] : 678.1659; found: 678.1646.
(2S,3R,4R,5R)-2-[4-(Benzoylamino)-6-oxo-1,6-dihydropyrimidin-1-yl]-5-
[(2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethoxy)methyl]tetrahy-
drofuran-3,4-diyl diacetate (10): BSA (0.38 mL, 1.55 mmol) was added
under Ar at 608C to a stirred suspension of 18 (160 mg, 0.75 mmol) and 7
(168 mg, 0.31 mmol) in MeCN (2 mL), and the resulting colorless solution
was stirred for 1 h at this temperature. TMSOTf (0.28 mL, 1.55 mmol) was
added, and the mixture was stirred at 608C for 50 min, then saturated
aqueous solutions of NaHCO3 (20 mL) and EtOAc (20 mL) were added.
The mixture was extracted with EtOAc (3 Â 50 mL), and the combined
organic phases were evaporated in vacuo. FC (SiO2 H, CH2Cl2/MeOH
N-(2-{[(2S,3R,4R,5R)-5-(6-Aminopurin-9-yl)-3,4-dihydroxytetrahydrofur-
an-2-yl]methoxy}ethyl)-2,3-dihydroxy-5-nitrobenzamide (1): A solution of
21 (48 mg, 0.07 mmol) in MeNH2 (25% in EtOH, 5 mL) was stirred for
30 min at 208C. After evaporation in vacuo, the orange residue was
dissolved in H2O (10 mL) and extracted three times each with Et2O
(10 mL), toluene (10 mL), and CH2Cl2 (10 mL). After lyophilization from
H2O, 1 (29 mg, 82%) was obtained as a yellow powder and shown by
analytical HPLC (H2O/MeCN/CF3COOH 90:10:0.1 !40:60:0.1) to be
pure. M.p. 1418C; [a]D20
16.0 (c 1.0, H2O); IR (KBr): nÄ 3422, 2944,
1639, 1556, 1500, 1472, 1422, 1333, 1261, 1122, 1072, 989, 828, 806, 700, 650,
100:1) afforded 10 as a white powder (0.11 g, 58%). M.p. 928C; [a]D20
1
556, 478, 406 cm 1; H NMR (300 MHz, CD3OD): d 8.48 (d, J 3.3 Hz,
33.0 (c 1.0, CHCl3); IR (KBr): nÄ 3342, 3056, 938, 1750, 1961, 1508,
1H), 8.45 (s, 1H), 8.18 (s, 1H), 7.50 (d, J 3.3 Hz, 1H), 6.06 (d, J 5.0 Hz,
1H), 4.69 (t, J 5.4 Hz, 1H), 4.49 (t, J 5.4 Hz, 1H), 4.22 ± 4.20 (m, 1H),
3.84 ± 3.65 (m, 6H); 13C NMR (125 MHz, D2O1 drop CD3OD): d
169.39, 156.83, 155.78, 153.12, 149.14, 148.47, 140.33, 133.03, 121.31,
119.21, 116.00, 108.74, 89.08, 84.70, 75.34, 71.37, 70.38, 70.18, 39.79; HR-
1
1444, 1372, 1329, 1243, 1094, 849, 760, 741 cm
;
1H NMR (300 MHz,
CDCl3): d 8.62 (s, 1H), 7.97 (s, 1H), 7.70 ± 7.16 (m, 14H), 6.34 (d, J
4.2 Hz, 1H), 5.82 ± 5.80 (m, 1H), 5.60 ± 5.55 (m, 2H), 4.54 ± 4.16 (m, 4H),
3.96 ± 3.34 (m, 6H), 2.14 (s, 3H), 2.12 (s, 3H); 13C NMR (125 MHz, CDCl3):
d 169.77, 169.57, 165.45, 161.44, 156.71, 154.01, 147.90, 143.89, 143.86,
141.28, 141.25, 133.14, 132.65, 128.98, 128.85, 127.70, 127.66, 127.18, 126.99,
126.95, 125.06, 124.95, 119.92, 98.24, 86.58, 81.68, 74.51, 70.83, 70.08, 69.20,
MS (FAB): calcd for C19H22N7O9 [MH] : 492.1479; found: 492.1460.
N-(2-{[(2S,3R,4R,5R)-5-(4-Amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-
dihydroxytetrahydrofuran-2-yl]methoxy}ethyl)-2,3-dihydroxy-5-nitroben-
zamide (2): Starting from 22 (48 mg, 0.07 mmol), the procedure described
for 1 gave 2 (28 mg, 82%) as an orange powder. M.p. 1668C; [a]2D0 15.0
66.71, 47.25, 41.06, 20.60, 20.50; MS (FAB): m/z (%): 719.2 (14) [MNa] ,
697.2 (100) [MH] ; HR-MS (FAB): calcd for C37H37N4O10 [MH] : 697.2509;
found: 697.2511.
(c 1.0, CHCl3); IR (KBr): nÄ 3412, 3211, 2922, 2878, 1646, 1561, 1494,
(2S,3R,4R,5R)-2-[6-(Benzoylamino)purin-9-yl]-5-({2-[(2,3-dihydroxy-5-
nitrobenzoyl)amino]ethoxy} methyl)tetrahydrofuran-3,4-diyl diacetate
(21): HNEt2 (40 mL) was added to 8 (100 mg, 0.14 mmol) in DMF
(40 mL), and the solution was stirred under Ar for 2.5 h at 208C. After
evaporation of HNEt2 in vacuo, 11 (41 mg, 0.14 mmol) and NEt3 (0.06 mL,
0.43 mmol) were added and the mixture was stirred for 24 h at 208C.
Evaporation in vacuo and recrystallization from 2-propanol gave 21 as an
1
1406, 1339, 1273, 1122, 1076, 989, 911, 789, 700, 600, 561 cm
;
1H NMR
(500 MHz, D2O): d 8.44 (d, J 3.0 Hz, 1H), 7.81 (d, J 7.6 Hz, 1H), 7.66
(d, J 3.0 Hz, 1H), 5.88 (d, J 4.0 Hz, 1H), 5.68 (d, J 7.6 Hz, 1H), 4.40 ±
4.37 (m, 1H), 4.30 ± 4.29 (m, 1H), 4.28 ± 4.24 (m, 1H), 4.00 (d, J 9.5 Hz,
1H), 3.90 ± 3.60 (m, 5H); 13C NMR (125 MHz, D2O1 drop of CD3OD):
d 169.83, 168.64, 166.67, 158.42, 149.10, 141.77, 132.77, 122.15, 116.60,
108.83, 96.62, 90.73, 83.91, 75.58, 70.52, 70.44, 70.03, 39.98; HR-MS (FAB):
orange powder (28 mg, 30%). M.p. 1278C; [a]D20
21.0 (c 1.0, THF); IR
calcd for C18H21N5O10Na [MNa] : 490.1186; found: 490.1176.
(KBr): nÄ 3411, 2922, 2344, 1744, 1700, 1639, 1611, 1583, 1516, 1460, 1336,
1241, 1073, 904, 792, 747, 708 cm 1; 1H NMR (500 MHz, CDCl3): d 8.71 (s,
1H), 8.69 (s, 1H), 8.43 (d, J 2.7 Hz, 1H), 8.06 (d, J 7.2 Hz, 2H), 7.67 ±
7.53 (m, 3H), 7.43 (d, J 2.7 Hz, 1H), 6.37 (d, J 5.7 Hz, 1H), 5.98 (t, J
5.7 Hz, 1H), 5.81 ± 5.78 (m, 1H), 4.29 ± 4.28 (m, 1H), 3.94 ± 3.59 (m, 6H),
2.15 (s, 3H), 2.00 (s, 3H); 13C NMR (125 MHz, CD3OD): d 170.09,
169.74, 168.52, 165.86, 152.33, 151.93, 151.53, 149.55, 146.74, 141.51, 133.22,
N-(2-[{(2S,3R,4R,5R)-5-[4-(Benzoylamino)-6-oxo-1,6-dihydropyrimidin-
1-yl]-3,4-dihydroxytetrahydrofuran-2-yl}methoxy]ethyl)-2,3-dihydroxy-5-
nitrobenzamide (24): Starting from 23 (30 mg, 0.05 mmol), the procedure
described for 1 provided 24 (21 mg, 80%) as an orange powder. M.p.
1428C; [a]2D0 7.0 (c 1.0, CHCl3); IR (KBr): nÄ 3421, 2933, 2867, 1683,
1
1656, 1550, 1508, 1444, 1333, 1261, 1122, 989, 844, 806, 700, 556 cm
;
980
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Chem. Eur. J. 2000, 6, No. 6