1
150
J. R. HWU ET AL.
(
10a, 48.7 mg, 0.250 mmol, 1.2 equiv.). After the solution was stirred at room temperature
for 15 min and then worked up, the residue was purified by use of column chromatography
15% methanol in CH2Cl2 as the eluant) to give 11a (81.4 mg, 0.172 mmol) in 83% yield
(
1
as white solids: H NMR (DMSO-d6, 400 MHz) δ: 10.63 (br, 1 H, NH), 7.95 (s, 1 H,
CH C COO), 7.62–7.56 (m, 2 H, 2 × ArH), 7.40 (d, J = 8.0 Hz, 1 H, ArH), 7.32 (dd,
ꢁꢁ
J = 7.6, 7.2 Hz, 1 H, ArH), 6.40 (s, 2 H, NH2), 5.70 (d, J = 6.4 Hz, 1 H, H-1 ), 5.35 (d,
J = 6.4 Hz, 1 H, OH), 5.05 (d, J = 4.8 Hz, 1 H, OH), 4.93 (dd, J = 6.4, 5.2 Hz, 1 H, OH),
ꢁ
ꢁ
ꢁ
4
4
(
.90–4.84 (m, 1 H, H-2 ), 4.25 (d, J = 13.8 Hz, 1 H, SCH), 4.20 (d, J = 13.8 Hz, 1 H, SCH),
ꢁ
ꢁꢁ
ꢁꢁ
.09–4.06 (m, 1 H, H-3 ), 3.80–3.77 (m, 1 H, H-4 ), 3.62–3.57 (m, 1 H, H-5 ), 3.50–3.44
m, 1 H, H-5 ); C NMR (DMSO-d6, 100 MHz) δ 160.12 (C O), 155.62, 153.11, 152.91,
ꢁꢁ
13
1
8
1
52.52, 141.69, 140.97, 131.74, 128.31, 124.69, 124.16, 118.85, 117.37, 116.09, 88.23,
5.75, 70.56, 70.54, 61.99, 32.67 (SCH2); IR (ATR) 3140 (br, OH), 2924 (w), 1711 (m),
−1
+
+
688 (s), 1608 (s), 1073 (s), 923 (m) cm ; MS (FAB ) m/z 474 (MH , 16), 342 (32), 219
+
(29), 105 (18), 97 (100); HRMS (FAB) Anal. Calcd. for (C20H19N5O7S + H) : 474.1083;
Found 474.1091.
ꢀ
ꢀ
8
-[(6 -Fluorocoumarin-3 -yl)methylthio]guanosine (11b). Standard proce-
dure 2 was followed by use of 9 (65.2 mg, 0.207 mmol, 1.0 equiv.) and 3-chloromethyl-
6-fluorocoumarin (10b, 52.8 mg, 0.248 mmol, 1.2 equiv). After the solution was stirred
at room temperature for 15 min and then worked up, the residue was purified by use of
column chromatography (15% methanol in CH2Cl2 as the eluant) to give 11b (92.4 mg,
0.188 mmol) in 91% yield as white solids: 1H NMR (DMSO-d6, 400 MHz) δ: 10.68 (br, 1
H, NH), 7.90 (s, 1 H, CH C COO), 7.53–7.42 (m, 3 H, 3 × ArH), 6.41 (s, 2 H, NH2),
ꢁ
ꢁ
5
1
.70 (d, J = 6.8 Hz, 1 H, H-1 ), 5.35 (d, J = 6.0 Hz, 1 H, OH), 5.07 (d, J = 4.8 Hz,
ꢁꢁ
H, OH), 4.94 (dd, J = 6.8, 5.2 Hz, 1 H, OH), 4.89–4.85 (m, 1 H, H-2 ), 4.24 (d, J = 14.0
ꢁꢁ
Hz, 1 H, SCH), 4.19 (d, J = 14.0 Hz, 1 H, SCH), 4.10–4.06 (m, 1 H, H-3 ), 3.80–3.76 (m,
ꢁꢁ
ꢁꢁ
ꢁꢁ 13
1
1
1
6
1
H, H-4 ), 3.62–3.56 (m, 1 H, H-5 ), 3.49–3.43 (m, 1 H, H-5 ); C NMR (DMSO-d6,
00 MHz) δ 159.83 (C O), 158.07 (d), 155.60, 153.10, 152.47, 149.25, 141.48, 139.84,
25.44, 119.81 (d), 118.83 (d), 118.00 (d), 117.42, 113.47 (d), 88.27, 85.74, 70.53, 70.50,
1.96, 32.77 (SCH2); IR (ATR) 3146 (br, OH), 2922 (w), 1723 (m), 1681 (s), 1626 (s),
−1
+
+
071(s) cm ; MS (FAB ) m/z 492 (MH , 35), 360 (62), 307 (98), 219 (23), 156 (100), 107
+
(
100); HRMS (FAB) Anal. Calcd. for (C20H18FN5O7S + H) : 492.0989; Found 492.0996.
ꢀ
ꢀ
8
-[(6 -Bromocoumarin-3 -yl)methylthio]guanosine (11c). Standard proce-
dure 2 was followed by use of 9 (62.2 mg, 0.197 mmol, 1.0 equiv.) and 6-bromo-3-
chloromethyl)coumarin (10c, 64.7 mg, 0.237 mmol, 1.2 equiv.). After the solution was
(
stirred at room temperature for 15 min and then worked up, the residue was purified by use
of column chromatography (15% methanol in CH2Cl2 as the eluant) to give 11c (85.7 mg,
0.155 mmol) in 79% yield as white solids: 1H NMR (DMSO-d6, 400 MHz) δ: 10.66 (br, 1
H, NH), 7.89 (s, 1 H, CH C COO), 7.88 (d, J = 2.4 Hz, 1 H, ArH), 7.73 (dd, J = 8.8,
2
1
6
.4 Hz, 1 H, ArH), 7.38 (d, J = 8.8 Hz, 1 H, ArH), 6.40 (s, 2 H, NH2), 5.70 (d, J = 6.8 Hz,
ꢁꢁ
H, H-1 ), 5.34 (d, J = 6.4 Hz, 1 H, OH), 5.06 (d, J = 4.8 Hz, 1 H, OH), 4.93 (dd, J =
ꢁꢁ
.8, 5.2 Hz, 1 H, OH), 4.89–4.85 (m, 1 H, H-2 ), 4.23 (d, J = 14.0 Hz, 1 H, SCH), 4.19 (d,
ꢁꢁ
ꢁꢁ
J = 14.0 Hz, 1 H, SCH), 4.10–4.06 (m, 1 H, H-3 ), 3.80–3.76 (m, 1 H, H-4 ), 3.62–3.56 (m,
ꢁꢁ
ꢁꢁ 13
1
1
1
2
3
H, H-5 ), 3.49–3.43 (m, 1 H, H-5 ); C NMR (DMSO-d6, 100 MHz) δ: 159.65 (C O),
55.70, 153.18, 152.52, 151.95, 141.46, 139.52, 134.03, 130.29, 125.50, 120.78, 118.39,
17.43, 116.24, 88.23, 85.77, 70.57, 70.54, 61.99, 32.80 (SCH2); IR (ATR) 3334 (br, OH),
920 (w), 1709 (s), 1692 (s), 1599 (s), 1066 (s) cm ; MS (FAB ) m/z 552 (MH , 12),
07 (36), 289 (25), 154 (100), 136 (74); HRMS (FAB) Anal. Calcd. for (C20H18BrN5O7S
−1
+
+
+
+
H) : 552.0189; Found 552.0180.