N, 27.25%); dH (250 MHz; DMSO-d6) 8.38 (1H, s, H-8), 8.15
(1H, s, H-2), 7.42 (2H, br s, NH2), 5.89 (1H, dd, J1 ,2 6.2, J1 ,C−1
164.3, H-1ꢀ), 5.51 (2H, m overlapping OH-2ꢀ and OH-5ꢀ), 5.25
(1H, d, J 6.2, J2 ,C−1 3.6, H-
3 ,3 −OH 4.5, OH-3ꢀ), 4.63 (1H, m, J1 ,2
2ꢀ), 4.15 (1H, m, J3 ,4 4.7, H-3ꢀ), 3.98 (1H, unresolved
3.1, J3 ,C−1
m, H-4ꢀ), 3.69 (1H, dt, J 5 a,5 b 12.1, H-5ꢀa) and 3.56 (1H,
4 ,5 a 4.1, J
dt, J5 b,4 3.7, J5 a,5 b
12.1, H-5ꢀb); (unlabelled: 8.37 (1H, s H-8),
8.15 (1H, s, H-2), 7.41 (2H, br s, NH2), 5.89 (1H, d, J1 ,2 6.2,
H-1ꢀ), 5.49 (2H, m, overlapping OH-2ꢀ and OH-5ꢀ), 5.25 (1H, d,
J3 ,3 −OH 6.2, J2 ,3
4.6, OH-3ꢀ), 4.63 (1H, m, J1 ,2 4.9, H-2ꢀ), 4.16
(1H, m, J2 ,3 4.9, J3 ,4 3.0 and J 6.0,
3.0, H-3ꢀ), 3.98 (1H, m J3 ,4
H-4ꢀ), 3.69 (1H, dt, J 5 a,5 b 12.0, H-5ꢀa) and 3.56 (1H, dt,
4 ,5 a 3.9, J
J4 ,5 b 3.7, J5 a,5 b
12.0, H-5ꢀb)); dC (62.9 MHz; DMSO-d6) 156.5
(C-6), 152.7 (C-2), 149.4 (C-4), 140.3 (C-8), 119.7 (C-5, d, J5,1
C10H13N5O4 requires C, 44.9; H, 4.9; N, 26.2%); dH (300 MHz;
DMSO-d6) 8.35 (1H, s, H-8), 8.19 (1H, s, H-2), 7.55 (2H, br s,
NH2), 5.90 (2H, m, overlapping OH-2ꢀ and OH-3ꢀ), 5.87 (1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
d, J1 ,2
4.31 (1H, unresolved m, H-2ꢀ), 4.16 (1H, m, J3 ,4
4 ,5 b 6.1, H-4ꢀ), 4.04 (1H, m, H-3ꢀ), 3.77 (1H, dd, J
11.5, H-5ꢀa) and 3.65 (1H, dd, J4 ,5 b 11.5, H-5ꢀb); dC
6.1, J5 a,5 b
ꢀ
ꢀ
1.6, H-1ꢀ), 4.73 (1H, t, J5 a,5 −OH
ꢀ
ꢀ
= J5 b,5 −OH
3.8, J4 ,5 a
4 ,5 a 4.9, J5 a,5 b
ꢀ
ꢀ
5.5, OH-5ꢀ),
4.9,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(62.9 MHz; DMSO-d6) 155.1 (C-6), 151.2 (C-2), 149.0 (C-4),
140.4 (C-8), 119.2 (C-5), 89.9 (C-1ꢀ), 84.1 (C-4ꢀ), 81.2 (C-2ꢀ),
75.5 (C-3ꢀ) and 59.8 (C-5ꢀ); m/z (ES) 268 (100%, M+ + H) and
136 ((M+ − C5H9O4) + H); Rf (90 : 10 chloroform–methanol)
0.06, (90 : 10 acetone–water) 0.65.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Synthesis of 9-(a-D-lyxofuranosyl)adenine 2920. This was
prepared from D-lyxose with final purification on a silica column
(70 : 30 chloroform–methanol) to give 29 (94 mg) as a very pale
yellow powder; dH (300 MHz; DMSO-d6) 8.37 (1H, s, H-8), 8.14
ꢀ
2.2), 88.3 (C-1ꢀ)*, 86.3 (C-4ꢀ), 73.8 (C-2ꢀ, d, J1 ,2 42.6), 71.0 (C-3ꢀ,
ꢀ
ꢀ
d, J1 ,3
ꢀ
ꢀ
3.5) and 62.0 (C-5ꢀ); m/z (EI) 269 (M+ + H), 251 (M+ −
OH), 238 (M+ − CH2OH), 179 (36%), 165 (74), 135 (100, M+ −
sugar), 119 (34, 135 − NH2); m/z (ES) 291 (100%, M+ + Na);
m/z (ES) 291.0896 (M+ + Na, required for C913CH13N5O4Na
291.0899, difference 1.0 ppm); Rf (90 : 10 acetone–water) 0.82,
(80 : 20 chloroform–methanol) 0.20.
(1H, s, H-2), 7.28 (2H, br s, NH2), 5.85 (1H, d, J1 ,2
1ꢀ), 5.49 (1H, br unresolved d, OH-2ꢀ), 5.18 (1H, br unresolved
d, OH-3ꢀ), 5.02 (1H, dd, J1 ,2 4.3, H-2ꢀ), 4.64 (1H, br
7.0, J2 ,3
unresolved d, OH-5ꢀ), 4.43 (1H, m, H-4ꢀ), 4.15 (1H, m, H-3ꢀ),
11.1, H-5ꢀa) and 3.53 (1H, m,
ꢀ
ꢀ
7.0, H-
ꢀ
ꢀ
ꢀ
ꢀ
3.66 (1H, dd, J4 ,5 a
ꢀ
ꢀ
4.8, J5 a,5 b
ꢀ
ꢀ
Synthesis of 9-(b-D-arabinofuranosyl)adenine 2621 (adapted
from ref. 22). At room temperature a solution of 9-(2ꢀ,3ꢀ,5ꢀ-
tri-O-benzyl-b-D-arabino-furanosyl)adenine (1.0 g, 1.86 mmol)
in methanol containing 10% formic acid (100 cm3) was added
to a stirred suspension of 10% Pd on carbon (2.0 g =
200 mg, 1.42 mmol Pd) in methanol containing 10% formic
acid (100 cm3). With monitoring by TLC, further additions of
formic acid (5 cm3) were made after 25 h and 66 h. After a total
of 72 h the catalyst was removed by filtration and washed with
methanol (ca. 500 cm3). The combined filtrates were evaporated
to leave a colourless oil (584 mg), which solidified on cooling
to room temperature. This was recrystallised from water and
then dried under vacuum over P2O5 to give 26 (387 mg, 78%) as
colourless needles (found: C, 42.35; H, 5.25; N, 25.5. C10H13N5O4
requires C, 44.9; H, 4.9; N, 26.2%); dH (250 MHz; DMSO-d6)
8.20 (1H, s, H-8), 8.14 (1H, s, H-2), 7.27 (2H, br s, NH2), 6.26
overlapping water, H-5ꢀb); dC (62.9 MHz; DMSO-d6) 158.9 (C-
6), 155.4 (C-2), 152.4 (C-4), 143.3 (C-8), 122.3 (C-5), 97.2 (C-1ꢀ),
90.4 (C-4ꢀ), 85.4 (C-2ꢀ), 77.4 (C-3ꢀ) and 62.7 (C-5ꢀ); m/z (FAB)
268 (M+ + H), 251 (M+ − NH2); m/z (ES) 268.1049 (M+ + H,
C10H14N5O4 requires 268.1046, difference 1.1 ppm); Rf (95 : 5
chloroform–methanol) 0.00, (90 : 10 acetone–water) 0.48.
Synthesis of 9-(b-D-glucopyranosyl)adenine 3025. 1,2,3,4,6-
Penta-O-acetyl-b-D-glucopyranoside (2.0 g, 5.12 mmol) was
coupled with adenine 7 (0.74 g, 5.51 mmol) using tin(IV)
chloride conditions with purification on a silica column (96 :
4 chloroform–methanol) to give 9-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-b-
D-glucopyranosyl)adenine (546 mg, 23%) as a colourless semi-
crystalline oil. Deprotection with sodium methoxide afforded 30
(132 mg, 44%) as a colourless powder; dH (300 MHz; DMSO-d6)
8.33 (1H, s, H-8), 8.16 (1H, s, H-2), 7.29 (1H, s, NH2), 5.41 (1H,
d, J1 ,2
ꢀ
ꢀ
9.2, H-1ꢀ), 4.01 (1H, t, J1 ,2
ꢀ
ꢀ
9.2, J2 ,3
8.9, H-2ꢀ), 3.71 (1H, d,
ꢀ
ꢀ
(1H, d, J1 ,2
(1H, d, J3 ,3 −OH
OH-5ꢀ), 4.13 (2H, m, overlapping H-2ꢀ and H-3ꢀ), 3.78 (1H, m,
ꢀ
ꢀ
4.4, H-1ꢀ), 5.68 (1H, d, J2 ,2 −OH
ꢀ
ꢀ
4.1, OH-2ꢀ), 5.61
= J5 b,5 −OH 5.2,
J5 ,6 a
ꢀ
ꢀ
10.4, H-6ꢀa) and 3.5 − 3.2 (4H, m, overlapping H-3ꢀ, H-4ꢀ,
ꢀ
ꢀ
4.1, OH-3ꢀ), 5.20 (1H, t, J5 a,5 −OH
ꢀ
ꢀ
ꢀ
ꢀ
H-5ꢀ and H-6ꢀb); dC (75.5 MHz; DMSO-d6) 156.3 (C-6), 153.0
(C-2), 150.1 (C-4), 140.1 (C-8), 119.0 (C-5), 83.1 (C-1ꢀ), 80.3
(C-5ꢀ), 77.6 (C-3ꢀ), 71.6 (C-2ꢀ), 70.1 (C-4ꢀ) and 61.2 (C-6ꢀ); m/z
(EI) 297 (M+), 280 (M+ − OH), 267 (M+ − CH2OH + H), 250
(M+ − CH2OH − OH + H), 135 (100%, M+ − sugar), 119 (16,
135 − NH2); m/z (ES) 298.1144 (M+ + H, C11H16N5O5 requires
298.1151, difference 2.3 ppm); Rf (90 : 10 acetone–water) 0.36.
J 4.3 and 8.3, H-4ꢀ) and 3.67 (2H, m, J4 ,5 a
ꢀ
ꢀ
4.1, J4 ,5 b 5.1, J5 a,5 b
ꢀ
ꢀ
ꢀ
ꢀ
9.2, H-5ꢀa and H-5ꢀb); dC (75.5 MHz; DMSO-d6) 156.2 (C-6),
152.8 (C-2), 149.7 (C-4), 140.6 (C-8), 118.5 (C-5), 84.4 (C-4ꢀ),
83.9 (C-1ꢀ), 76.0 (C-2ꢀ), 75.3 (C-3ꢀ) and 61.2 (C-5ꢀ); m/z (FAB)
268 (100%, M+ + H); m/z (EI) 268.106 (M+ + H, C10H13N5O4
requires 268.105, difference 3.7 ppm); Rf (90 : 10 acetone–water)
0.60.
The strategy for the synthesis of the following compounds 27
to 29 from the free sugar is the same as that shown for adenosine
1 in Scheme 1.
Acknowledgements
We thank the Engineering and Physical Sciences Research
Council (EPSRC) for a studentship (S.G.P.) and the EU, the
Medical Research Council (MRC), the Wellcome Trust, the
Biotechnology and Biological Sciences Research Council (BB-
SRC), GlaxoSmithKline, the Royal Society and the University
of Leeds for support of this research. This work was carried
out as part of the BBSRC funded North of England Structural
Biology Centre. We thank Professor So Iwata (Imperial College,
London) for providing the coordinates of the LacY structure
prior to publication, and Professor Steve W. Homans (University
of Leeds) for discussion.
Synthesis of 9-(a-D-arabinofuranosyl)adenine 2718. This was
prepared from D-arabinose with final purification on a silica
column (80 : 20 chloroform–methanol) to give 27 (34 mg) as
a colourless powder; dH (250 MHz; DMSO-d6) 8.24 (1H, s, H-
8), 8.06 (1H, s, H-2), 7.22 (2H, br s, NH2), 5.75 (1H, d, J1 ,2
5.1, H-1ꢀ), 4.59 (1H, t, J2 ,3 5.0, H-3ꢀ), 4.08 (1H, m, H-
= J3 ,4
4ꢀ), 3.89 (1H, t, J 6.0, H-2ꢀ) and 3.52 (2H, m, J4 ,5 a
3.7, J4 ,5 b
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
4.9, H-5ꢀa and H-5ꢀb); dC (75.5 MHz; DMSO-d6) 156.4 (C-6),
152.9 (C-2), 149.6 (C-4), 140.4 (C-8), 119.6 (C-5), 88.7 (C-1ꢀ),
85.6 (C-4ꢀ), 79.7 (C-3ꢀ), 75.6 (C-2ꢀ) and 61.5 (C-5ꢀ); m/z (EI) 267
(M+), 250 (M+ − OH), 236 (M+ − CH2OH), 135 (100%, M+ −
C5H9O4 + H) and 43 (88, CH3CO+); m/z (ES) 268.0956 (M+ +
H, C10H14N5O4 requires 268.1046, difference 33.6 ppm); Rf (90 :
10 chloroform–methanol) 0.08, (90 : 10 acetone–water) 0.66.
References
1 P. J. F. Henderson, in The Transporter Factsbook, ed. J. K. Griffith
and C. E. Sansom, Academic Press, London, 1998.
2 J. E. Craig, Y. Zhang and M. P. Gallagher, Mol. Microbiol., 1994, 11,
1159.
3 S. E. Westh Hansen, N. Jensen and A. Munch-Peterson,
Eur. J. Biochem., 1987, 168, 385.
Synthesis of 9-(b-D-xylofuranosyl)adenine 2819. This was
prepared from D-xylose with final recrystallisation from 95%
ethanol and drying under vacuum over P2O5 to give 28 (52 mg)
as a colourless powder (found: C, 45.2; H, 5.0; N, 26.05.
4 M. W. L. Ritzel, S. Y. M. Yao, M.-Y. Huang, J. F. Elliot, C. E. Cass
and J. D. Young, Am. J. Physiol., 1997, 272, C707.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 6 2 – 4 7 0
4 6 9