2-Amino-5-(2-deoxy-ꢁ-D-ribofuranosyl)pyridine 23
5-(2-Deoxy-3,5-di-O-acetyl-ꢀ(ꢁ)-D-ribofuranosyl)-2-dibenzyl-
amino-3-methylpyridines 27 and 28
Ammonium cerium() nitrate (1.60 g, 2.9 mmol) was added
to a stirred solution of 5-(2-deoxy-3,5-di-O-acetyl-α--ribo-
furanosyl)-2-(dibenzylamino)pyridine 22a (0.35 g, 0.74 mmol)
in acetonitrile–water (98 : 2 v/v; 6 cm3) at room temperature.
After 25 min, the products were worked-up and chromato-
graphed as in the preparation of the β-isomer 2a (see (a) above)
to give a residual oil (0.15 g). A solution of this material (0.20 g,
from two batches) in ethanol (0.8 cm3) was treated as above
with 8 M ethanolic methylamine (0.84 cm3, 6.7 mmol) at room
temperature. After 16 h, the products were worked-up and
chromatographed as in the preparation of the β-isomer (see (a)
above) to give the title compound 23 (0.11 g, 53%) (HRMS
A 1.0 M solution of tetraethylammonium fluoride in aceto-
nitrile (15 cm3, 15 mmol) was added to a stirred solution
of 5-[2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-
β(α)--ribofuranosyl]-2-dibenzylamino-3-methylpyridines 26
(2.42 g, 3.74 mmol) in acetonitrile (5 cm3) at room temperature.
After 1.5 h, the products were worked up as in the above prep-
aration of 5-(2-deoxy-3,5-di-O-acetyl-β(α)--ribofuranosyl-2-
(dibenzylamino)pyridines 21a and 22a to give a colourless oil.
This material was evaporated from pyridine (3 × 10 cm3) solu-
tion and was then redissolved in pyridine (20 cm3). 1-Methyl-
imidazole (0.89 cm3, 11.2 mmol) and acetic anhydride (2.12
cm3, 22.5 mmol) were added to the stirred solution at room
temperature. After 1.5 h, methanol (3 cm3) was added and, after
a further period of 10 min, the products were concentrated
under reduced pressure. The residue was partitioned between
dichloromethane (50 cm3) and saturated aqueous sodium
hydrogen carbonate (2 × 30 cm3). The dried (MgSO4) organic
layer was evaporated under reduced pressure. The residue was
fractionated by short column chromatography into two com-
ponents which were both eluted with dichloromethane–meth-
anol (99.5 : 0.5 v/v). Fractions containing the first eluted major
component were combined and evaporated under reduced
pressure to give 5-(2-deoxy-3,5-di-O-acetyl-β--ribofuranosyl)-
2-dibenzylamino-3-methylpyridine 27 (0.86 g, 47%) (HRMS
1
Found: (M ϩ H)ϩ, 211.1082. 12C10 H1414N216O3 requires: (M ϩ
H)ϩ, 211.1083) as a colourless oil; δH[(CD3)2SO] 1.73 (1 H, m),
2.41 (1 H, m), 3.40 (1 H, dd, J 5.4 and 11.6), 3.50 (1H, dd, J 3.8
and 11.6), 3.76 (1 H, m), 4.17 (1 H, m), 4.69 (1 H, br), 4.75 (1 H,
dd, J 6.5 and 8.9), 5.05 (1 H, br), 5.86 (2 H, br s), 6.42 (1 H, d,
J 8.5), 7.42 (1 H, dd, J 2.4 and 8.5), 7.84 (1 H, d, J 2.1);
δC[(CD3)2SO] 43.16, 62.09, 72.02, 77.10, 86.29, 108.09, 126.43,
136.03, 146.22, 159.56. In the NOESY spectrum of 2-amino-5-
(2-deoxy-α--ribofuranosyl)pyridine 23: (a) cross-peaks are
observed only between the higher field (presumed α) H-2Ј
(δ 1.73) and the H-4 (δ 7.42) and H-6 (δ 7.84) resonance signals;
(b) strong cross peaks are observed between the lower field
(presumed β) H-2Ј (δ 2.41) and the H-1Ј (δ 4.75) and H-3Ј
(δ 4.17) resonance signals; (c) the cross-peak between the H-1Ј
and H-3Ј resonance signals is stronger than that between the
H-1Ј and H-4Ј (δ 3.76) resonance signals; (d) a cross-peak is
observed between only the higher field H-2Ј resonance signal
and that of H-4Ј.
1
Found: (M ϩ H)ϩ, 489.2402. 12C29 H3314N216O5 requires: (M ϩ
H)ϩ, 489.2389) as a colourless oil; δH[CDCl3] 1.99 (1 H, m), 2.01
(3 H, s), 2.04 (3 H, s), 2.21 (1 H, dd, J 5.1 and 13.7), 2.33 (3 H,
s), 4.13 (1 H, m), 4.19 (1 H, m), 4.26 (4 H, s), 4.29 (1 H, dd, J 3.8
and 11.5), 4.95 (1 H, dd, J 5.0 and 10.9), 5.15 (1 H, d, J 6.5),
7.16 (10 H, m), 7.35 (1 H, d, J 2.1), 8.01 (1 H, d, J 2.2);
δC[CDCl3] 19.35, 21.26, 21.48, 41.11, 54.78, 64.84, 76.97, 78.86,
82.95, 125.81, 127.20, 128.58, 128.61, 129.75, 137.86, 139.34,
143.85, 161.82, 170.96, 171.08.
5-[2-Deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-
ꢀ(ꢁ)-D-ribofuranosyl]-2-dibenzylamino-3-methylpyridines 26
Later fractions containing the minor component were
combined and evaporated under reduced pressure to give 5-(2-
deoxy-3,5-di-O-acetyl-α--ribofuranosyl)-2-dibenzylamino-3-
methylpyridine 28 (0.14 g, 7.7%) (HRMS Found: (M ϩ H)ϩ,
489.2363) as a colourless oil; δH[CDCl3] 1.93 (3 H, s), 2.01 (1 H,
m), 2.04 (3 H, s), 2.34 (3 H, s), 2.69 (1 H, m), 4.17 (2 H, m), 4.26
(4 H, s), 4.31 (1 H, m), 5.01 (1 H, t, J 7.3), 5.14 (1 H, m), 7.15
(10 H, m), 7.40 (1 H, d, J 2.1), 8.02 (1 H, d, J 2.3); δC[CDCl3]
18.94, 20.95, 20.98, 39.84, 54.50, 63.99, 75.70, 77.92, 81.47,
125.40, 126.83, 128.22, 128.25, 130.69, 137.60, 139.03, 143.32,
161.16, 170.63, 170.81.
n-Butyllithium (1.6 M in hexane, 15.7 cm3, 25.1 mmol) was
added to a stirred solution of 5-bromo-2-dibenzylamino-3-
methylpyridine 25 (9.25 g, 25.2 mmol) in dry THF (100 cm3) at
Ϫ78 ЊC (acetone–dry ice bath). After 40 min, a pre-cooled (to
Ϫ78 ЊC) solution of 2-deoxy-(1,1,3,3-tetraisopropyldisiloxan-
1,3-diyl)--ribofuranose 15 (3.39 g, 9.00 mmol) in THF
(40 cm3) was added. The reactants were stirred at Ϫ78 ЊC for
1 h, and were then allowed to warm up to 0 ЊC over a period of
3 h. The products were then worked up and chromatographed
as in the above preparation of 5-[2-deoxy-3,5-O-(1,1,3,3-tetra-
isopropyldisiloxan-1,3-diyl)-β(α)--ribofuranosyl]-2-(dibenzyl-
amino)pyridines 19a to give a colourless oil (3.95 g). Diiso-
propyl azodicarboxylate (2.92 cm3, 14.8 mmol) was added
dropwise to a stirred solution of this material and triphenyl-
phosphine (3.90 g, 14.9 mmol) in THF (60 cm3) at 0 ЊC (ice–
water bath). After 3 h, a 0.5 M solution of iodine in dichloro-
methane was added dropwise until the iodine coloration just
persisted. The products were then worked-up and fractionated
as in the above preparation of 5-[2-deoxy-3,5-O-(1,1,3,3-tetra-
isopropyldisiloxan-1,3-diyl)-β(α)--ribofuranosyl]-2-(dibenzyl-
amino)pyridine 19a to give the title compounds 26 as a colour-
2-Amino-5-(2-deoxy-ꢀ-D-ribofuranosyl)-3-methylpyridine 2b
Ammonium cerium() nitrate (2.88 g, 5.25 mmol) was added
to a stirred solution of 5-(2-deoxy-3,5-di-O-acetyl-β--ribo-
furanosyl)-2-dibenzylamino-3-methylpyridine 27 (0.86 g, 1.76
mmol) in acetonitrile–water (98 : 2 v/v, 20 cm3) at room temper-
ature. After 25 min, the products were worked up and fraction-
ated as in the above preparation of 2-amino-5-(2-deoxy-β--
ribofuranosyl)pyridine 2a to give a colourless oil (0.41 g). This
material was dissolved in ethanol (1.6 cm3) and an 8 M solution
of methylamine in ethanol (1.62 cm3, 13.0 mmol) was added
to the stirred solution at room temperature. After 16 h, the
products were worked up and chromatographed as in the above
preparation of 2-amino-5-(2-deoxy-β--ribofuranosyl)pyridine
less oil (2.42, 41.5% overall yield; β : α ratio ca. 1.5 : 1) (HRMS
12
Found: (M ϩ H)ϩ, 647.3681.
C
1H5514N216O428Si2 requires:
37
(M ϩ H)ϩ, 647.3700); δH[CDCl3] 0.99 (28 H, m), 2.05 (1 H, m),
2.23 (0.6 H, m), 2.31 (1.8 H, s), 2.33 (1.2 H, s), 2.51 (0.4 H, m),
3.81 (2 H, m), 3.96 (0.4 H, dd, J 2.5 and 10.8), 4.02 (0.6 H, dd,
J 2.2 and 10.2), 2.34 (4 H, s), 4.49 (1 H, m), 4.84 (0.4 H, dd,
J 5.9 and 10.0), 4.95 (0.6 H, t, J 7.2), 7.14 (10 H, m), 7.34 (0.6 H,
d, J 2.1), 7.45 (0.4 H, d, J 2.1), 7.99 (1 H, s); δC[CDCl3] 12.94,
12.99, 13.29, 13.39, 13.74, 13.84, 13.91, 17.37, 17.43, 17.46,
17.52, 17.56, 17.67, 17.72, 17.79, 17.83, 17.86, 17.94, 17.97,
19.21, 19.25, 42.93, 43.01, 54.84, 63.75, 64.05, 73.95, 74.20,
76.68, 77.34, 84.00, 86.85, 125.85, 127.15, 128.58, 128.63,
131.30, 131.86, 137.88, 139.43, 143.77, 161.50.
2a to give the title compound 2b (0.23 g, 58%) (HRMS Found:
12
Mϩ, 224.1156.
C
1H1614N216O3 requires: Mϩ, 224.1161) as a
11
colourless glass; δH[(CD3)2SO] 1.81 (1 H, m), 1.94 (1 H, m), 2.03
(3 H, s), 3.42 (2 H, m), 3.70 (1 H, m), 4.17 (1 H, m), 4.75 (1 H,
br), 4.82 (1 H, dd, J 5.3 and 10.5), 5.03 (1 H, br), 5.66 (2 H, br
s), 7.23 (1 H, d, J 1.4), 7.73 (1 H, d, J 2.0); δC[(CD3)2SO] 17.42,
43.16, 62.84, 72.82, 77.64, 87.83, 115.94, 125.84, 135.86, 143.65,
158.23.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 1 6 0 – 3 1 7 2
3170