F. Diederich, Markus G. Rudolph et al.
filtered, and concentrated in vacuo. The residue was purified by flash
chromatography (SiO2; CH2Cl2/MeOH 98:2!95:5) to give 7 as a color-
less foam (192 mg, 44%).
ACHTUNGTRENNUNG
[a]2D0 =+16 (c=0.59, CHCl3); 1H NMR (300 MHz, CDCl3: d=2.01 (s,
3H), 2.02 (s, 3H), 4.26 (d, J=5.5 Hz, 2H), 4.58–4.54 (m, 1H), 5.09 (ddd,
J=12.2, 7.8, 4.2 Hz, 2H), 5.38 (d, J=4.9 Hz, 1H), 5.80 (dd, J=15.6,
5.8 Hz, 1H), 5.87–5.96 (m, 1H), 6.29 (d, J=7.8 Hz, 2H), 7.38 (d, J=
7.9 Hz, 2H), 7.63–7.67 (m, 2H), 7.72–7.77 ppm (m, 2H); 13C NMR
(75 MHz, CDCl3): d=20.48, 20.59, 38.73, 72.66, 73.99, 81.65, 94.26,
118.79, 123.27, 128.16, 129.25, 131.70, 134.10, 136.26, 167.49, 169.19,
169.25, 179.42 ppm; IR (neat): n˜ =2939 w, 1749 m, 1712 s, 1638 m, 1582
m, 1490 w, 1466 w, 1426 w, 1394 m, 1240 s, 1185 m, 1110 w, 1051 w, 951 w,
897 w, 851 w, 756 m, 722 m, 629 mcmꢁ1; HR-MALDI-MS (3-HPA): m/z
[a]2D0 =ꢁ49 (c=1.03, CHCl3); 1H NMR (300 MHz, CDCl3): d=2.07 (s,
6H), 4.29–4.27 (m, 2H), 4.60–4.64 (m, 1H), 5.19 (t, J=4.8 Hz, 1H), 5.33
(t, J=5.2 Hz, 1H), 5.57 (d, J=5.4 Hz, 1H), 5.77 (ddt, J=15.4, 5.8, 1.2 Hz,
1H), 5.94 (dtd, J=15.4, 5.9, 1.2 Hz, 1H), 7.29 (d, J=6.2 Hz, 2H), 7.71
(dd, J=5.5, 3.1 Hz, 2H), 7.83 (dt, J=5.6, 2.8 Hz, 2H), 8.42 ppm (d, J=
6.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=20.74, 20.81, 38.85, 73.92,
74.13, 82.71, 85.60, 122.77, 123.39, 128.04, 129.85, 132.00, 134.05, 146.04,
149.52, 167.63, 169.21, 169.54 ppm; IR (neat): n˜ =2934 w, 1749 m, 1712 s,
1574 m, 1541 w, 1483 w, 1467 w, 1427 w, 1394 m, 1378 w, 1237 s, 1100 w,
1049 w, 948 w, 900 w, 804 w, 756 w, 722 m, 629 m cmꢁ1; HR-MALDI-MS
(3-HPA): m/z (%): 483.1228 (100, calcd for C24H23N2O7S+ [M+H]+:
483.1221).
+
(%): 467.1456 (100, calcd for C24H23N2O8 [M+H]+: 467.1449).
6-Chloro-9-[(5E)-2,3-di-O-acetyl-5,6,7-trideoxy-7-phthalimido-b-d-ribo-
hept-5-enofuranosyl]purine (10): A dry N2-flushed Schlenk tube (20 mL),
equipped with a magnetic stirrer and a septum, was charged with 6-
chloroACHTUNGTRENNUNGpurine (452 mg, 2.92 mmol), toluene (12 mL), and N,O-bis(trime-
thylsilyl)acetamide (0.59 mL, 2.44 mmol). The mixture was heated to
608C. After 30 min, the mixture was cooled to 208C and then 5 (420 mg,
0.97 mmol) and trimethylsilyl trifluoromethanesulfonate (1.06 mL,
5.85 mmol) were added slowly. The mixture was heated to 608C, stirred
for 20 h, and then cooled to 208C. Afterwards, a saturated aqueous solu-
tion of NaHCO3 (200 mL) and CH2Cl2 (200 mL) were added and the ob-
tained phases separated. The aqueous phase was extracted with CH2Cl2
(2ꢅ200 mL), the combined organic phases were dried (MgSO4), filtered,
and concentrated in vacuo. The residue was purified twice by flash chro-
matography (SiO2; CH2Cl2/MeOH 97:3) (SiO2; hexane/EtOAc 1:1) to
give 10 as a yellow oil (432 mg, 84%).
5-[(5E)-2,3-Di-O-acetyl-5,6,7-trideoxy-7-phthalimido-b-d-ribo-hept-5-
enofuranosyl]-5H-pyrrolo
tube (20 mL), equipped with a magnetic stirrer and a septum, was
charged with 5H-pyrrolo[3,2-c]pyridine (62.4 mg, 52.89 mmol), N,O-bis-
(trimethylsilyl)acetamide (0.22 mL, 88.14 mmol), and 1,2-dichloroethane
ACHTUNGTRENN[UGN 3,2-c]pyridine (17): A dry N2-flushed Schlenk
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(7.5 mL). The mixture was heated to 608C. After 30 min, the mixture was
cooled to 208C and then 5 (0.19 g, 44.07 mmol) in dry 1,2-dichloroethane
(7.5 mL), and trimethylsilyl trifluoromethanesulfonate (0.32 mL,
1.76 mmol) were added slowly. The mixture was heated to 608C, stirred
for 20 h, and then cooled to 208C. Afterwards, H2O (100 mL) and
CH2Cl2 (100 mL) were added and the obtained phases were separated.
The aqueous phase was extracted with CH2Cl2 (2ꢅ100 mL), the com-
bined organic phases were dried (MgSO4), filtered, and concentrated in
vacuo. The residue was purified by flash chromatography (SiO2; CH2Cl2/
MeOH 40:1) to give product 17 as a red oil (92.4 mg, 43%).
[a]2D0 =+20 (c=0.59, CHCl3); 1H NMR (400 MHz, CDCl3): d=2.06 (s,
3H), 2.14 (s, 3H), 4.34 (m, 2H), 4.67 (t, J=4.4 Hz, 1H), 5.53 (t, J=
5.1 Hz, 1H), 5.97 (m, 3H), 6.14 (d, J=5.1 Hz, 1H), 7.74 (m, 2H), 7.86
(m, 2H), 8.21 (s, 1H), 8.69 ppm (s, 1H); 13C NMR (101 MHz, CDCl3):
d=20.37, 20.54, 38.64, 72.77, 73.55, 82.34, 87.06, 123.46, 128.68, 129.18,
132.01, 132.50, 134.17, 143.96, 151.26, 151.63, 152.30, 167.69, 169.32,
169.51 ppm; IR (neat): n˜ =2360 s, 2341 s, 1717 m, 1609 w, 1512 m, 1465 s,
1247 s, 1209 s, 1171 s, 1025 s, 1004 m, 933 s, 828 s, 780 m, 720 w, 668 w,
w ; HR-ESI-MS: m/z (%): 548.0936 (100, calcd for
cmꢁ1
+
[a]2D0 =ꢁ4 (c=0.1, CHCl3); 1H NMR (300 MHz, CDCl3: d=2.15 (s, 6H),
4.42 (dd, J=1.7, 4.5 Hz, 2H), 4.90 (t, J=5.5 Hz, 1H), 5.23 (t, J=5.3 Hz,
1H), 5.34 (dd, J=4.2, 5.2 Hz, 1H), 6.05 (m, 2H), 6.30 (d, J=4.1 Hz, 1H),
7.02 (dd, J=0.7, 3.4 Hz, 1H), 7.68 (d, J=3.4 Hz, 1H), 7.75 (m, 2H), 7.88
(m, 2H), 8.09 (d, J=7.1 Hz, 1H), 8.26 (dd, J=1.5, 7.1 Hz, 1H), 9.05 ppm
(d, J=1.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=20.51, 22.66, 38.92,
72.35, 75.93, 83.11, 96.94, 105.04, 110.83, 123.24, 123.42, 125.20, 127.47,
129.66, 131.06, 131.70, 133.38, 134.09, 134.26, 167.71, 169.86, 172.66 ppm;
IR (neat): n˜ =3463 m, 3331 m, 3133 m, 2360 s, 1708 s, 1392 m, 1239 s,
1025 m, 970 w, 718 s, 632 s cmꢁ1; HR-MALDI-MS (3-HPA): m/z (%):
635
C24H20ClN5NaO7 [M+Na]+: 548.0943).
9-[(5E)-2,3-Di-O-acetyl-5,6,7-trideoxy-7-phthalimido-b-d-ribo-hept-5-
enofuranosyl]-6-methylpurine (12):
A dry N2-flushed Schlenk tube
(20 mL), equipped with a magnetic stirrer and a septum, was charged
with 6-methylpurine (186 mg, 1.39 mmol), 1,2-dichloroethane (9 mL), and
N,O-bis(trimethylsilyl)acetamide (0.25 mL, 1.04 mmol). The mixture was
heated to 608C. After 30 min, the mixture was cooled to 208C and then 5
(300 mg, 0.70 mmol) and trimethylsilyl trifluoromethanesulfonate
(0.38 mL, 1.04 mmol) were added slowly. The mixture was heated to
808C for 4 h, stirred at 708C for 18 h, and then cooled to 208C. After-
wards, a saturated aqueous solution of NaHCO3 (200 mL) and CH2Cl2
(200 mL) were added and the obtained phases separated. The aqueous
phase was extracted with CH2Cl2 (2ꢅ200 mL), the combined organic
phases were dried (MgSO4), filtered, and concentrated in vacuo. No pu-
rification was needed to give 12 as a yellow oil (349 mg, 99%).
+
490.1615 (100, calcd for C26H24N3O7 [M+H]+: 490.1609).
1-[(5E)-5,6,7-Trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-b-d-ribo-
hept-5-enofuranosyl]benzo[d]imidazole (18): Nucleoside
6
(24 mg,
0.024 mmol) was dissolved in a solution of methylamine (2 mL, 33% in
ethanol) and stirred for 16 h at 208C. Afterwards, the solvents were re-
moved in vacuo. The residue was dissolved in MeOH, filtered, and puri-
fied by reverse-phase HPLC (H2O/MeCN/HCOOH 90:10:0.01!
20:80:0.01) to give the allylamine, which was dissolved in DMF (1 mL).
Compound 4 (16 mg, 0.054 mmol) and Et3N (0.04 mL) were added, and
the mixture was stirred at 208C for 24 h. The mixture was purified twice
by reverse-phase HPLC (H2O/MeCN/HCOOH 90:10:0.01!20:80:0.01)
to give product 18 as a yellow solid (9 mg, 42%).
M.p. 76–808C (decomp); [a]2D0 =+ 10 (c=0.35, Me2SO); 1H NMR
(500 MHz, (CD3)2SO): d=4.00–4.03 (m, 3H), 4.46 (m, 2H), 5.84–5.89
(m, 1H), 5.95 (dd, J=15.5, 6.9 Hz, 1H), 6.01 (d, J=5.1 Hz, 1H), 7.38–
7.41 (m, 2H), 7.72 (d, J=2.7 Hz, 1H), 7.76 (m, 2H), 8.45 (d, J=2.7 Hz,
1H), 8.89 (s, 1H), 9.44–9.46 ppm (m, 1H); 13C NMR ((CD3)2SO,
125 MHz): d=40.43, 73.30, 73.56, 84.29, 89.48, 112.02, 112.16, 114.36,
114.54, 117.95, 123.84, 124.07, 129.38, 129.42, 131.77, 138.41, 141.47,
146.92, 156.12, 157.89, 158.16, 167.90 ppm; IR (neat): n˜ =3259 br, 2973 w,
1670 s, 1548 w, 1515 m, 1474 w, 1448 w, 1327 s, 1284 s, 1197 s, 1131 s, 1096
[a]2D0 =+23 (c=0.84, CHCl3); 1H NMR (400 MHz, CDCl3): d=1.96 (s,
3H), 2.04 (s, 3H), 2.75 (s, 3H), 4.24 (m, 2H), 4.57 (t, J=4.5 Hz, 1H),
5.47 (t, J=5.1 Hz, 1H), 5.88–5.92 (m, 3H), 6.07 (d, J=5.1 Hz, 1H), 7.64
(m, 2H), 7.75 (m, 2H), 8.04 (s, 1H), 8.68 ppm (s, 1H); 13C NMR
(101 MHz, CDCl3): d=19.56, 20.44, 20.61, 38.75, 72.87, 73.69, 82.15,
86.63, 123.47, 128.99, 129.07, 132.11, 133.81, 134.16, 142.47, 150.22, 152.58,
159.86, 167.74, 169.37, 169.57 ppm; IR (neat): n˜ =2962 w, 1748 m, 1709 s,
1599 m, 1499 w, 1467 w, 1426 w, 1393 m, 1371 m, 1336 m, 1236 w, 1209 s,
1046 m, 944 m, 892 m, 828 w, 795 w, 720 s, 644 w cmꢁ1; HR-ESI-MS: m/z
+
(%): 506.1678 (85, calcd for C25H24N5O7 [M+H]+: 506.1670), 528.1500
+
(100, calcd for C25H23NaN5O7 [M+Na]+: 528.1490).
Pyridin-4-yl (5E)-2,3-Di-O-acetyl-5,6,7-trideoxy-7-phthalimido-1-thio-b-
d-ribo-hept-5-enofuranoside (14):
A dry N2-flushed flask (25 mL),
equipped with a magnetic stirrer and a septum, was charged with 4-thio-
pyridine (154 mg, 1.39 mmol), MeCN (3 mL), and N,O-bis(trimethylsil-
6378
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6369 – 6381