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N. J. Greco, Y. Tor / Tetrahedron 63 (2007) 3515–3527
(400 MHz, DMSO-d6): d 11.93 (s, NH, 1H), 8.82 (s, H-6,
1H), 7.85 (d, J¼3.2 Hz, H-500, 1H), 7.65 (d, J¼3.2 Hz, H-
400, 1H), 6.21 (t, J¼6.6 Hz, H-10, 1H), 5.29 (d, J¼4.4 Hz,
30-OH, 1H), 5.01 (t, J¼5.0 Hz, 50-OH, 1H), 4.29–4.25 (m,
H-30, 1H), 3.88–3.86 (m, H-40, 1H), 3.61–3.58 (m, H-50,
2H), 2.23–2.19 (m, H-20, 2H); 13C NMR (100 MHz,
DMSO-d6): d 161.3 (C-4), 158.1 (C-200), 149.4 (C-2),
141.8 (C-400), 138.5 (C-6), 119.8 (C-500), 107.6 (C-5), 87.8
(C-40), 85.3 (C-10), 70.5 (C-30), 61.3 (C-50), 40.1 (C-20);
ESI-MS calcd for C12H13N3NaO5S [M+Na]+ 334.05, found
333.94; UV (buffer) lmax¼316 nm (3¼11,500).
4.1.8. 8-(Fur-2-yl)-adenosine (3). To a suspension of 11
(208 mg, 0.6 mmol) and ammonium sulfate (43 mg) in
anhydrous 1,1,1,3,3,3-hexamethyldisilazane (20 ml) was
added anhydrous pyridine (2 ml). The reaction was refluxed
under argon overnight. Solvent was removed under reduced
pressure and the resulting oil was used without further
purification. To a solution of the resulting trimethylsilyl
protected nucleoside and dichlorobis(triphenylphosphine)-
Pd(II) (28 mg, 0.04 mmol) in anhydrous tetrahydrofuran
(10 ml) was added 2-(tributylstannyl)furan (950 ml, 1.0 g,
3.0 mmol) in a pressure tube and was heated to 90 ꢂC for
24 h. Solvent was removed under reduced pressure and the
resulting oil run through a silica plug with 5% methanol/di-
chloromethane. The resulting oil was taken up in methanol
(5 ml) to which potassium carbonate (500 mg, 3.6 mmol)
was added. The reaction was allowed to stir at room temper-
ature overnight. Solid was filtered off and the product was
recrystallized from methanol. Resulting white solid was
run through a silica plug using 50/50 water/acetonitrile to
remove any remaining potassium carbonate. Product: white
solid (18.6 mg, 0.056 mmol, 9% yield). 1H NMR (400 MHz,
DMSO-d6): d 8.13 (s, H-2, 1H), 8.01 (d, J¼2.4 Hz, H-500,
1H), 7.58 (br s, 6-NH2, 2H), 7.13 (d, J¼4.8 Hz, H-300, 1H),
6.77–6.76 (m, H-400, 1H), 6.10 (d, J¼8.8 Hz, H-10, 1H),
5.77 (dd, J¼4.4 and 12 Hz, 50-OH, 1H), 5.46 (d, J¼8.4 Hz,
20-OH, 1H), 5.21 (d, J¼5.6 Hz, 30-OH, 1H), 5.14–5.08 (m,
H-20, 1H), 4.21–4.17 (m, H-30, 1H), 3.98 (d, J¼2.4 Hz, H-
40, 1H), 3.72–3.67 (m, H-50, 1H), 3.51–3.49 (m, H-50, 1H);
13C NMR (100 MHz, DMSO-d6): d 156.3 (C-6), 152.3 (C-
2), 149.6 (C-4), 145.6 and 143.3 (C-200 and C-500), 141.5
(C-8), 119.4 (C-5), 113.9 and 112.1 (C-300 and C-400), 89.3
(C-10), 86.7 (C-40), 71.6 (C-20), 71.0 (C-30), 62.2 (C-50);
ESI-MS calcd for C14H16N5O5 [M+H]+ 334.12, found
334.02; UV (buffer) lmax¼304 nm (3¼18,000).
4.1.6. 30,50-Di-O-acetyl-5-(fur-2-yl)-20-deoxyuridine (10).
To a solution of 1 (1.0 g, 3.5 mmol) in anhydrous pyridine
(15 ml) was added acetic anhydride (825 ml, 891 mg,
8.73 mmol). The reaction was allowed to stir under argon
at room temperature overnight. Solvent was removed under
reduced pressure. Resulting oil was taken up in chloroform
(200 ml) and washed with 1 M HCl (3ꢀ100 ml) and water
(100 ml). The organic layer was dried over sodium sulfate
and the solvent removed under reduced pressure. Product:
1
light orange foam (1.34 g, 3.5 mmol, 99% yield). H NMR
(400 MHz, CDCl3): d 8.60 (s, NH, 1H), 7.97 (s, H-6, 1H),
7.32 (d, J¼1.6 Hz, H-500, 1H), 7.05 (d, J¼3.2 Hz, H-300,
1H), 6.45 (q, J¼2 and 3.2 Hz, H-300, 1H), 6.41 (td, J¼5.6
and 8.8 Hz, H-10, 1H), 5.28–5.26 (m, H-30, 1H), 4.38–4.37
(m, H-50, 2H), 4.29 (q, J¼3 and 5 Hz, H-40, 1H), 2.55–
2.50 (m, H-20, 1H), 2.28–2.19 (m, H-20, 1H), 2.14 (s, Ac,
3H), 2.11 (s, Ac, 3H); 13C NMR (100 MHz, CD3Cl):
d 170.1 (Ac carbonyl), 170.0 (Ac carbonyl), 159.2 (C-4),
148.9 (C-2), 145.4 (C-200), 140.9 (C-500), 132.2 (C-6), 112.0
(C-400), 109.7 (C-300), 107.7 (C-5), 85.2 (C-40), 82.5 (C-10),
74.6 (C-30), 64.1 (C-50), 38.1 (C-20), 21.0 (Ac methyl), 20.8
(Ac methyl); d ESI-MS calcd for C17H19N2O8 [M+H]+
379.11, found 378.84 and for C17H18N2NNaO8 [M+Na]+
401.10, found 401.00.
4.1.9. 8-(Fur-2-yl)-guanosine (4). To a suspension of 12
(139 mg, 0.4 mmol) and ammonium sulfate (21 mg) in
anhydrous 1,1,1,3,3,3-hexamethyldisilazane (10 ml) was
added anhydrous pyridine (1 ml). The reaction was stirred
under argon and refluxed overnight. Solvent was removed
under reduced pressure and the resulting oil was used
without further purification. To a solution of the resulting tri-
methylsilyl protected nucleoside and dichlorobis(triphenyl-
phosphine)Pd(II) (8.5 mg, 0.01 mmol) in anhydrous
tetrahydrofuran (10 ml) was added 2-(tributylstannyl)furan
(600 ml, 680 mg, 1.9 mmol) in a pressure tube and was
heated to 90 ꢂC for 24 h. Solvent was removed under re-
duced pressure and the resulting oil run through a silica
plug with 5% methanol/dichloromethane. The resulting oil
was taken up in methanol (5 ml) to which potassium carbon-
ate (300 mg, 2.2 mmol) was added. The reaction was al-
lowed to stir at room temperature overnight. Solid was
filtered off and the product was recrystallized from metha-
nol. Resulting white solid was run through a silica plug using
50/50 water/acetonitrile to remove any remaining potassium
carbonate. Product: white solid (13.8 mg, 0.04 mmol, 10%
4.1.7. 5-(Fur-2-yl)-20-deoxycytidine (2). To a solution of
10 (800 mg, 2.1 mmol), 2,4,6-triisopropylbenzenesulfonyl
chloride (2.0 g, 6.72 mmol), and 4-dimethylaminopyridine
(825 mg, 6.72 mmol) in anhydrous acetonitrile (70 ml)
was added triethylamine (937 ml, 680 mg, 6.72 mmol).
The reaction was allowed to stir under argon at room tem-
perature for 36 h. Once all starting material was consumed
(monitored by TLC), concentrated ammonium hydroxide
(90 ml) was added to the reaction flask. The reaction was
again allowed to stir at room temperature overnight. Solvent
was removed under reduced pressure. Resulting solid was
taken up in cold chloroform and solid filtered off. Product:
1
off white solid (590 mg, 2.0 mmol, 95% yield). H NMR
(400 MHz, DMSO-d6): d 8.25 (s, H-6, 1H), 7.68–7.67 (m,
H-500, 1H), 7.64 (br s, 4-NH2, 1H), 6.65 (br s, 4-NH2,
1H), 6.57–6.54 (m, H-400 and H-300, 2H), 6.16 (t,
J¼6.4 Hz, H-10, 1H), 5.22 (d, J¼4 Hz, 30-OH, 1H), 5.08
(t, J¼4.8 Hz, 50-OH, 1H), 4.24–4.20 (m, H-30, 1H), 3.80–
3.78 (m, H-40, 1H), 3.64–3.54 (m, H-50, 2H), 2.20–2.15
(m, H-20, 1H), 2.07–2.01 (m, H-20, 1H); 13C NMR
(100 MHz, DMSO-d6): d 161.5 (C-4), 153.5 (C-2), 147.2
(C-200), 142.3 (C-500), 139.6 (C-6), 111.3 (C-400), 106.5
(C-300), 98.0 (C-5), 87.3 (C-40), 85.2 (C-10), 69.9 (C-30),
60.9 (C-50), 40.8 (C-20); ESI-MS calcd for C13H16N3O5
[M+H]+ 294.11, found 293.84; UV (buffer) lmax¼306 nm
(3¼5000).
1
yield). H NMR (400 MHz, DMSO-d6): d 10.83 (s, 1-NH,
1H), 7.90 (d, J¼1.6 Hz, H-500, 1H), 6.94 (d, J¼3.2 Hz, H-
300, 1H), 6.68 (q, J¼1.7 Hz, H-400, 1H), 6.46 (br s, 2-NH2,
2H), 5.91 (d, J¼6.4 Hz, H-10, 1H), 5.38 (d, J¼6.0 Hz, 20-
OH, 1H), 5.04–4.96 (m, 30-OH, 50-OH, and H-20, 3H),
4.13–4.08 (m, H-30, 1H), 3.84 (dt, J¼4.8 and 8.8 Hz, H-40,
1H), 3.68–3.63 (m, H-50, 1H), 3.54–3.48 (m, H-50, 1H);