2.19, 2.14 and 2.09 (all 3H, s, acetates); δH (dimer 5, obtained
from mixtures with its monomer 4) 8.08 (1H, s, 8-H), 6.34 (1H,
d, J 6.5, 1Ј-H), 6.04 (2H, br s, NH2), 5.58 (1H, dd, J 5.8 and 6.5,
2Ј-H), 5.45 (1H, dd, J 2.4 and 5.8, 3Ј-H), 4.6–4.4 (3H, m, 4Ј-H
and 5Ј-H2), 2.22, 2.17 and 2.14 (all 3H, s, acetates).
isomers) was obtained. KCN (26 mg, 0.40 mmol) was added
and after ca. 1 h crystallisation started. This KCN-catalysed
deprotection was in general complete after 6 h, but filtration
of the product at this stage of the reaction gave much lower
yields of the crystalline isomer and the filtrate consisted mainly
of the second isomer. When stirring was continued for 48 h
12 was obtained as a single isomer by filtration (0.633 g,
87%), mp >200 ЊC (decomp.) (Found: C, 49.66; H, 4.95; N,
23.08. C15H18N6O5 requires C, 49.72; H, 5.01; N, 23.19%);
δH (d6-DMSO) 8.09 (1H, s, 8-H), 7.16 (2H, s, NH2), 6.36 (1H,
m, 5Љ-H or 6Љ-H), 6.24 (1H, m, 6Љ-H or 5Љ-H), 5.76 (1H, d, J 5.6,
1Ј-H), 5.40 (1H, d, J 6.2, 2Ј-OH), 5.36 (1H, m, 1Љ-H or 4Љ-H),
5.20 (1H, m, 4Љ-H or 1Љ-H), 5.15 (1H, d, J 4.5, 3Ј-OH), 5.02 (1H,
dd, J 7.0 and 4.8, 5Ј-OH), 4.67 (1H, m, 2Ј-H), 4.17 (1H,
m, 3Ј-H), 3.93 (1H, m, 4Ј-H), 3.64 (1H, m, 5Ј-Ha), 3.55 (1H, m,
5-Hb), 1.93 (1H, d, J 8.3, 7Љ-Ha), 1.71 (1H, d, J 8.3, 7Љ-Hb);
m/z (FABϩ) 363 (Mϩ ϩ 1, 4%), 307 (33), 289 (27), 154 (100) and
136 (96) (Found: Mϩ ϩ 1, 363.1413. C15H19N6O5 requires m/z,
363.1317).
2-(Hydroxyamino)adenosine 6
Aq. ammonia (25%; 3 mL) was added to a solution of 3 (0.20 g,
0.47 mmol) in methanol (3 mL) and the resulting solution was
stirred at rt for 16 h. The mixture was evaporated and the resi-
due was coevaporated twice with ethanol. Trituration with a
small amount of ethanol produced 6 (0.114 g, 81%) as a solid,
mp 185–195 ЊC; δH (d6-DMSO) 8.56 (1H, br, NHOH), 8.27 (1H,
br, NHOH), 8.03 (1H, s, 2-H), 6.96 (2H, br, NH2), 5.80 (1H, d,
J 6.8, 1Ј-H), 5.39 (1H, d, J 6.1, OH), 5.20 (1H, d, J 5.0, OH),
5.14 (1H, d, J 5.6, OH), 4.59 (1H, dd, J 6.8 and 5.3, 2Ј-H),
4.18 (1H, m, 3Ј-H), 3.98 (1H, m, 4Ј-H), 3.60 (2H, m, 5Ј-H2);
δC (d6-DMSO) 162.8, 156.2, 155.9, 151.0, 137.1, 114.8, 86.9,
85.7, 73.2, 70.8 and 64.9; m/z (FABϩ) 299 (Mϩ ϩ 1, 22%), 217
(62), 154 (100) and 136 (87) (Found: Mϩ ϩ 1, 299.1103.
C10H15N6O5 requires m/z 299.1104).
When this NMR sample was heated for a short time at 50 ЊC
complete isomerisation occurred and a 1 : 1 mixture of two
isomers 12 was formed. From the second isomer only two pro-
ton signals were observed separately at 500 MHz (d6-DMSO):
δH 5.06 (1H, m, 5Ј-OH) and 4.61 (1H, m, 2Ј-H).
2Ј,3Ј,5Ј-Tris-O-(tert-butyldimethylsilyl)-2-nitroadenosine 9
A solution of 2-nitroadenosine 8 (0.106 g, 0.5 mmol), TBDM-
SCl (0.377 g, 2.5 mmol) and imidazole (0.198 g, 3.0 mmol) in
DMF (3 mL) was stirred for 42 h at room temperature. Extrac-
tive work-up using water and diethyl ether followed by tritur-
ation with methanol produced 9 (0.271 g, 83%): mp 92–96 ЊC;
νmax/cmϪ1 (KBr) 1490, 1345; δH 8.45 (s, 1H, 8-H), 7.39 (br, s, 2H,
NH2), 5.99 (d, 1H, J 4.2, H-1Ј), 4.66 (dd, 1H, J 4.2, 4.3, 2Ј-H),
4.33 (m, 1H, 3Ј-H), 4.18 (m, 1H, 4Ј-H), 4.15 (m, 1H, 5Ј-Ha),
3.83 (m, 1H, 5Ј-Hb), 0.15, 0.14, 0.09, 0.08, 0.01, Ϫ0.10 (6 s,
SiCH3); δC 152.4, 152.1, 151.1, 148.0, 134.8, 89.6, 85.6, 76.2,
71.1, 61.8, 25.7, 25.4, 18.4, 17.9, Ϫ4.10, Ϫ4.58, Ϫ4.59, Ϫ4.76,
Ϫ5.13 and Ϫ5.28.
2-Nitrosoadenosine 7
A vigorous stream of N2 was led through a solution of 12
(0.2 g, 0.55 mmol) in anhydrous DMF (8 mL) at 95 ЊC (bath
temperature). After 15 min the solvent was evaporated off and
the residue was crystallised from water (ca. 3 mL) to give 7
(0.072 g) as a yellow crystalline solid. The filtrate was evapor-
ated, and the residue was thermolyzed in DMF (3 mL) as
described before to give a combined yield of 0.094 mg of title
compound 7 (58%), mp >250 ЊC (decomp.) (Found: C, 40.40;
H, 4.10; N, 28.21. C10H12N6O5 requires C, 40.54; H, 4.08;
N, 28.37%); λmax/nm (H2O) 247, 311, 400; νmax/cmϪ1 (KBr) 1655,
1597, 1492, 1365 and 1330; δH monomer (d6-DMSO; 70 ЊC,
1 mg in 0.6 mL; monomer : dimer = 1 : 1) 8.68 (1H, s, 2-H), 7.7
(2H, s, NH2), 6.05 (1H, d, J 5.6, 1Ј-H), 5.33 (1H, d, J 5.6, OH),
4.99 (1H, m, OH), 4.87 (1H, m, OH), 4,67 (1H, m, 2Ј-H), 4.24
(1H, m, 3Ј-H), 4.02 (1H, m, 4Ј-H), 3.62–3.75 (2H, m, 5Ј-H2);
δH dimer 8.43 (1H, s, 8-H), 7.8 (2H, br, NH2), 5.64 (1H, d, J 5.6,
1Ј-H), 5.54 (1H, d, J 6.1, OH), 5.17 (1H, m, OH), 5.10 (1H, m,
OH), 4.32 (1H, m, 2Ј-H), 4.09 (1H, m, 3Ј-H), 3.88 (1H, m,
4Ј-H), 3.65–3.55 (2H, m, 5Ј-H2); distinct 13C NMR spectra of 4
or 5 could not be obtained; with FAB techniques the Mϩ or
Mϩ ϩ 1 ion could not be detected.
2Ј,3Ј,5Ј-Tris-O-(tert-butyldimethylsilyl)-2-nitrosoadenosine 10
A mixture of 9 (0.171 g, 0.261 mmol) and 10% Pd/C (10 mg) in
EtOAc (10 mL) was stirred at 45–50 ЊC (bath temperature)
under hydrogen (1 atm). After 3 h the catalyst was removed by
filtration and the resulting solution was cooled to 0 ЊC. An ice-
cold solution of sodium periodate (0.075 g, 0.35 mmol) in 30
mL of water was added and the mixture was stirred vigorously
for 30 min. Separation of the layers, drying of the organic layer
(Na2SO4), and trituration of the residue obtained after evapor-
ation produced 10 (0.116 g, 69%) as a yellow solid: mp >180 ЊC
(decomp.); δH (mixture of monomer and dimer, selected
signals): 8.61 (s, 1H, 8-H monomer), 8.31 (s, 1H, 8-H dimer),
6.32 (d, J 4.3, 1Ј-H monomer), 5.72 (d, J 4.1, 1Ј-H dimer).
2-(cis-3-Hydroxycyclopentylamino)adenosine 13
A suspension of 12 (0.048 g, 0.13 mmol) and 10% Pd/C (10 mg)
in a mixture of ethanol (3 mL) and water (2 mL) was stirred
under 1 atm hydrogen for 24 h. Chromatography on silica, and
elution with EtOAc–MeOH 4 : 1, gave 13 (0.035 g, 74%) as a
white solid, mp 131–151 ЊC; δH (d6-DMSO) 7.90 (1H, s, 8-H),
6.72 (2H, s, NH2), 6.01 (1H, d, J 8.2, NH), 5.72 (1H, d, J 6.0,
1Ј-H), 5.37 (1H, br, OH), 5.13 (1H, br, OH), 4.64 (1H, m, 2Ј-H),
4.60 (1H, br, OH), 4.21 (1H, br, OH), 4.13 (2H, m), 3.90 (1H, m,
4Ј-H), 3.5–3.7 (2H, m, 5Ј-H2), 2.10 (1H, m), 1.90 (1H, m), 1.65–
1.75 (3H, m), 1.44 (1H, m); m/z (FABϩ) 367 (Mϩ ϩ 1, 55%), 235
(25), 154 (100) and 136 (96) (Found: Mϩ ϩ 1, 367.1735.
C15H23N6O5 requires m/z, 367.1722).
2Ј,3Ј,5Ј-Tri-O-acetyl-2-(2-oxa-3-azabicyclo[2.2.1]hept-5-en-3-
yl)adenosine 11
Cyclopentadiene (30 µL, 0.5 mmol) was added to a suspension
of 4 (0.085 g, 0.2 mmol) in DCM (2 mL). After stirring of the
mixture for 30 min the volatiles were removed by evaporation,
yielding pure 11 (quantitative) as a glass (inseparable 1 : 1 mix-
ture of isomers). The 1H NMR spectrum could not be resolved
except for the signals for 8-H, δH 7.70 and 7.64; δC 170.5, 170.4,
169.5, 169.42, 169.4, 169.3, 162.7, 155.7, 155.6, 150.3, 150.2,
136.0, 135.4, 133.2, 132.9, 116.2, 116.0, 87.39, 86.82, 83.39,
83.37, 79.50, 79.48, 73.10, 72.85, 70.19, 70.17, 65.93, 65.92,
63.15, 62.70, 48.16, 48.02, 20.62, 20.55, 20.43, 20.39 and 20.38.
2Ј,3Ј,5Ј-Tri-O-acetyl-2-(cis-4-hydroxycyclohexylamino)
adenosine 15
2-(2-Oxa-3-azabicyclo[2.2.1]hept-5-en-3-yl)adenosine 12
Cyclohexa-1,3-diene (19 µL, 0.2 mmol) was added to a suspen-
sion of 4 (0.042 g, 0.1 mmol) in DCM (2 mL). After stirring of
the mixture for 30 min the volatiles were removed by evapor-
ation, leaving pure 2Ј,3Ј,5Ј-tri-O-acetyl-2-(2-oxa-3-azabicyclo-
Direct preparation via 11: a suspension of 4 (0.844 g, 2.0 mmol)
in methanol (25 mL) was stirred with cyclopentadiene (0.248
mL, 3 mmol) for 1 h until a clear solution of 11 (1 : 1 mixture of
J. Chem. Soc., Perkin Trans. 1, 2001, 1908–1915
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