Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270105041983/tr1128sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270105041983/tr1128Isup2.hkl |
CCDC reference: 299637
The benzoyl-protected derivative of compound (I) was synthesized in nitromethane with BF3 etherate as catalyst. The glycosylation of 4-amino-1H-pyrazolo[3,4-d]pyrimidine (Robins, 1956) with 2-O-methyl-1,3,5-tri-O-benzoyl-α-D-ribofuranose (Chavis et al., 1982) furnished two regioisomers, viz. 4-amino-1-[2-O-methyl-(3,5-di-O-benzoyl)- β-D-ribofuranosyl]-1H-pyrazolo[3,4-d]pyrimidine, (V), and 4-amino-2- [2-O-methyl-(3,5-di-O-benzoyl)-β-D-ribofuranosyl]-1H-pyrazolo[3,4-d] pyrimidine, (VI). The regioisomer (VI) (650 mg, 1.3 mmol) was deprotected in methanol saturated with ammonia (60 ml) at room temperature overnight. Flush chromatography (silica gel; column 10 × 4 cm; CH2Cl2/CH3OH 4:1) furnished the title compound (I) as colourless foam (240 mg, 66%). Crystallization from a methanol–water mixture gave the title compound (m.p. 422–424 K). TLC (CH2Cl2/CH3OH 4:1) Rf = 0.5. UV (MeOH): 238 (6400). 1H NMR ((D6 DMSO): 8.57 (s, 1H, H—C6), 8.15 (s, 1H, H—C3), 7.71 (br s, 2H, NH2), 6.04 (d, 1H, J = 3.7 Hz, H—C1'), 5.25 (d, 1H, J = 5.9 Hz, HO—C3'), 4.94 (t, 1H, J = 5.5 Hz, HO—C5'), 4.30 (dd, 1H, J1 = 10.5 Hz, J2 = 5.2 Hz, H—C3'), 4.17 (t, 1H, J = 4.2 Hz, H—C2'), 4.00 (dd, 1H, J1 = 9.0 Hz, J2 = 4.7 Hz, H—C4'), 3.70–3.49 (m, 2H, H—C5'), 3.38 (s, 3H, OCH3).
In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absotute structure. Refinement of the Flack (1983) parameter led to inconclusive values (Flack & Bernardinelli, 2000) for this parameter [0.6 (9)]. Therefore, Friedel equivalents (282) were merged before the final refinements. The known configuration of the parent molecule was used to define the enantiomer employed in the refined model. All H atoms were initially found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, the H atoms were placed in geometrically idealized positions (C—H= 0.93–0.98 Å, O—H= 0.82 Å and N—H= 0.86 Å) and constrained to ride on their parent atoms with Uiso(H) values of 1.2Ueq(C,N) and 1.5Ueq(O). Please check treatment of O-bound H atoms.
Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997); program(s) used to solve structure: SHELXTL; program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 1999).
C11H15N5O4·H2O | F(000) = 632 |
Mr = 299.30 | Dx = 1.455 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: C 2y | Cell parameters from 42 reflections |
a = 17.263 (2) Å | θ = 4.8–12.5° |
b = 7.5673 (7) Å | µ = 0.12 mm−1 |
c = 10.4757 (8) Å | T = 293 K |
β = 93.128 (8)° | Block, colourless |
V = 1366.4 (2) Å3 | 0.54 × 0.4 × 0.3 mm |
Z = 4 |
Bruker P4 diffractometer | Rint = 0.018 |
Radiation source: fine-focus sealed tube | θmax = 31.0°, θmin = 2.0° |
Graphite monochromator | h = −1→24 |
2θ/ω scans | k = −10→1 |
2836 measured reflections | l = −15→15 |
2318 independent reflections | 3 standard reflections every 97 reflections |
2225 reflections with I > 2/s(I) | intensity decay: none |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.036 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.108 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0802P)2 + 0.1324P] where P = (Fo2 + 2Fc2)/3 |
2318 reflections | (Δ/σ)max < 0.001 |
201 parameters | Δρmax = 0.29 e Å−3 |
4 restraints | Δρmin = −0.16 e Å−3 |
C11H15N5O4·H2O | V = 1366.4 (2) Å3 |
Mr = 299.30 | Z = 4 |
Monoclinic, C2 | Mo Kα radiation |
a = 17.263 (2) Å | µ = 0.12 mm−1 |
b = 7.5673 (7) Å | T = 293 K |
c = 10.4757 (8) Å | 0.54 × 0.4 × 0.3 mm |
β = 93.128 (8)° |
Bruker P4 diffractometer | Rint = 0.018 |
2836 measured reflections | 3 standard reflections every 97 reflections |
2318 independent reflections | intensity decay: none |
2225 reflections with I > 2/s(I) |
R[F2 > 2σ(F2)] = 0.036 | 4 restraints |
wR(F2) = 0.108 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.00 | Δρmax = 0.29 e Å−3 |
2318 reflections | Δρmin = −0.16 e Å−3 |
201 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.39800 (7) | 0.6512 (2) | 0.44054 (12) | 0.0372 (3) | |
C2 | 0.33762 (9) | 0.6695 (2) | 0.35419 (13) | 0.0375 (3) | |
H2 | 0.3503 | 0.6630 | 0.2692 | 0.045* | |
N3 | 0.26362 (8) | 0.6953 (2) | 0.37155 (11) | 0.0385 (3) | |
C4 | 0.24802 (9) | 0.6997 (2) | 0.49826 (13) | 0.0325 (3) | |
C5 | 0.30550 (7) | 0.6797 (2) | 0.59851 (12) | 0.0310 (3) | |
C6 | 0.38344 (8) | 0.6554 (2) | 0.56538 (13) | 0.0343 (3) | |
N6 | 0.44266 (8) | 0.6404 (3) | 0.65129 (14) | 0.0481 (4) | |
H6A | 0.4891 | 0.6283 | 0.6266 | 0.058* | |
H6B | 0.4346 | 0.6427 | 0.7315 | 0.058* | |
C7 | 0.26568 (8) | 0.6964 (2) | 0.70996 (12) | 0.0343 (3) | |
H7A | 0.2863 | 0.6906 | 0.7938 | 0.041* | |
N8 | 0.19129 (6) | 0.7226 (2) | 0.67070 (11) | 0.0325 (2) | |
N9 | 0.17754 (7) | 0.7260 (2) | 0.54209 (11) | 0.0369 (3) | |
C1' | 0.12367 (8) | 0.7428 (2) | 0.74915 (12) | 0.0317 (3) | |
H1' | 0.0893 | 0.8349 | 0.7125 | 0.038* | |
C2' | 0.07852 (8) | 0.5693 (2) | 0.75991 (14) | 0.0347 (3) | |
H2' | 0.0842 | 0.4917 | 0.6861 | 0.042* | |
O2' | 0.00028 (6) | 0.6043 (2) | 0.78236 (12) | 0.0446 (3) | |
C2'O | −0.04690 (10) | 0.6348 (4) | 0.66917 (19) | 0.0540 (5) | |
H2'1 | −0.0260 | 0.7314 | 0.6226 | 0.081* | |
H2'2 | −0.0987 | 0.6633 | 0.6914 | 0.081* | |
H2'3 | −0.0480 | 0.5304 | 0.6171 | 0.081* | |
C3' | 0.11598 (9) | 0.4924 (2) | 0.88289 (15) | 0.0370 (3) | |
H3'1 | 0.1663 | 0.4410 | 0.8648 | 0.044* | |
O3' | 0.07012 (10) | 0.3626 (2) | 0.93787 (19) | 0.0600 (4) | |
H3' | 0.0978 (18) | 0.352 (7) | 1.002 (2) | 0.090* | |
C4' | 0.12912 (8) | 0.6576 (2) | 0.96354 (13) | 0.0338 (3) | |
H4' | 0.0804 | 0.6913 | 1.0006 | 0.041* | |
O4' | 0.15030 (7) | 0.79132 (17) | 0.87390 (10) | 0.0365 (2) | |
C5' | 0.19197 (10) | 0.6434 (3) | 1.06849 (16) | 0.0455 (4) | |
H5'1 | 0.1810 | 0.5452 | 1.1242 | 0.055* | |
H5'2 | 0.2414 | 0.6215 | 1.0318 | 0.055* | |
O5' | 0.19587 (8) | 0.8025 (2) | 1.14011 (12) | 0.0493 (3) | |
H5' | 0.2174 | 0.7836 | 1.2105 | 0.074* | |
O10 | 0.07920 (16) | 0.0607 (3) | 1.07967 (19) | 0.0786 (6) | |
H10A | 0.068 (3) | 0.070 (9) | 0.9897 (13) | 0.118* | |
H10B | 0.116 (2) | −0.028 (5) | 1.110 (4) | 0.118* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0281 (5) | 0.0511 (7) | 0.0328 (5) | 0.0004 (5) | 0.0066 (4) | 0.0034 (5) |
C2 | 0.0355 (7) | 0.0487 (8) | 0.0287 (5) | 0.0006 (6) | 0.0064 (5) | 0.0015 (6) |
N3 | 0.0322 (5) | 0.0578 (8) | 0.0257 (5) | 0.0021 (6) | 0.0019 (4) | 0.0020 (5) |
C4 | 0.0270 (5) | 0.0438 (7) | 0.0267 (5) | −0.0005 (5) | 0.0014 (4) | 0.0009 (5) |
C5 | 0.0225 (5) | 0.0438 (7) | 0.0268 (5) | 0.0000 (5) | 0.0021 (4) | 0.0021 (5) |
C6 | 0.0251 (5) | 0.0456 (8) | 0.0322 (6) | −0.0007 (5) | 0.0035 (4) | 0.0039 (6) |
N6 | 0.0249 (5) | 0.0845 (12) | 0.0348 (6) | 0.0026 (7) | 0.0022 (4) | 0.0034 (7) |
C7 | 0.0247 (5) | 0.0508 (8) | 0.0274 (5) | 0.0007 (5) | 0.0012 (4) | 0.0033 (6) |
N8 | 0.0232 (5) | 0.0478 (7) | 0.0266 (5) | 0.0014 (5) | 0.0024 (4) | 0.0025 (5) |
N9 | 0.0258 (5) | 0.0579 (8) | 0.0269 (5) | 0.0028 (5) | 0.0001 (4) | 0.0017 (5) |
C1' | 0.0259 (5) | 0.0419 (7) | 0.0276 (5) | 0.0031 (5) | 0.0041 (4) | 0.0004 (5) |
C2' | 0.0244 (5) | 0.0452 (8) | 0.0348 (6) | 0.0004 (5) | 0.0038 (4) | −0.0037 (6) |
O2' | 0.0221 (4) | 0.0719 (9) | 0.0400 (5) | 0.0015 (5) | 0.0035 (4) | 0.0039 (6) |
C2'O | 0.0306 (7) | 0.0834 (15) | 0.0472 (9) | 0.0015 (9) | −0.0044 (6) | 0.0038 (10) |
C3' | 0.0306 (6) | 0.0393 (7) | 0.0414 (7) | 0.0022 (5) | 0.0055 (5) | 0.0038 (6) |
O3' | 0.0558 (8) | 0.0524 (8) | 0.0724 (10) | −0.0076 (7) | 0.0096 (7) | 0.0214 (8) |
C4' | 0.0284 (5) | 0.0448 (7) | 0.0285 (5) | 0.0048 (5) | 0.0046 (4) | 0.0021 (5) |
O4' | 0.0402 (5) | 0.0412 (5) | 0.0284 (4) | −0.0040 (5) | 0.0041 (4) | −0.0022 (4) |
C5' | 0.0396 (7) | 0.0615 (11) | 0.0349 (6) | 0.0105 (8) | −0.0032 (5) | 0.0019 (7) |
O5' | 0.0515 (7) | 0.0621 (8) | 0.0332 (5) | 0.0013 (7) | −0.0080 (4) | 0.0023 (6) |
O10 | 0.1197 (18) | 0.0606 (10) | 0.0554 (9) | 0.0317 (12) | 0.0059 (10) | 0.0026 (8) |
N1—C6 | 1.3455 (18) | C2'—C3' | 1.525 (2) |
N1—C2 | 1.349 (2) | C2'—H2' | 0.9800 |
C2—N3 | 1.315 (2) | O2'—C2'O | 1.420 (2) |
C2—H2 | 0.9300 | C2'O—H2'1 | 0.9600 |
N3—C4 | 1.3691 (18) | C2'O—H2'2 | 0.9600 |
C4—N9 | 1.3386 (19) | C2'O—H2'3 | 0.9600 |
C4—C5 | 1.4130 (19) | C3'—O3' | 1.405 (2) |
C5—C7 | 1.3925 (17) | C3'—C4' | 1.519 (2) |
C5—C6 | 1.4196 (17) | C3'—H3'1 | 0.9800 |
C6—N6 | 1.3295 (19) | O3'—H3' | 0.806 (10) |
N6—H6A | 0.8600 | C4'—O4' | 1.4412 (19) |
N6—H6B | 0.8600 | C4'—C5' | 1.506 (2) |
C7—N8 | 1.3416 (17) | C4'—H4' | 0.9800 |
C7—H7A | 0.9300 | C5'—O5' | 1.418 (3) |
N8—N9 | 1.3555 (15) | C5'—H5'1 | 0.9700 |
N8—C1' | 1.4718 (17) | C5'—H5'2 | 0.9700 |
C1'—O4' | 1.4101 (17) | O5'—H5' | 0.8200 |
C1'—C2' | 1.534 (2) | O10—H10A | 0.954 (10) |
C1'—H1' | 0.9800 | O10—H10B | 0.97 (4) |
C2'—O2' | 1.4086 (17) | ||
C6—N1—C2 | 118.08 (12) | O2'—C2'—H2' | 112.5 |
N3—C2—N1 | 130.04 (13) | C3'—C2'—H2' | 112.5 |
N3—C2—H2 | 115.0 | C1'—C2'—H2' | 112.5 |
N1—C2—H2 | 115.0 | C2'—O2'—C2'O | 113.74 (13) |
C2—N3—C4 | 112.44 (13) | O2'—C2'O—H2'1 | 109.5 |
N9—C4—N3 | 124.51 (13) | O2'—C2'O—H2'2 | 109.5 |
N9—C4—C5 | 112.06 (12) | H2'1—C2'O—H2'2 | 109.5 |
N3—C4—C5 | 123.42 (13) | O2'—C2'O—H2'3 | 109.5 |
C7—C5—C4 | 104.75 (12) | H2'1—C2'O—H2'3 | 109.5 |
C7—C5—C6 | 137.27 (12) | H2'2—C2'O—H2'3 | 109.5 |
C4—C5—C6 | 117.94 (12) | O3'—C3'—C4' | 114.71 (15) |
N6—C6—N1 | 118.58 (13) | O3'—C3'—C2' | 113.02 (14) |
N6—C6—C5 | 123.34 (13) | C4'—C3'—C2' | 101.50 (13) |
N1—C6—C5 | 118.07 (12) | O3'—C3'—H3'1 | 109.1 |
C6—N6—H6A | 120.0 | C4'—C3'—H3'1 | 109.1 |
C6—N6—H6B | 120.0 | C2'—C3'—H3'1 | 109.1 |
H6A—N6—H6B | 120.0 | C3'—O3'—H3' | 95 (3) |
N8—C7—C5 | 105.34 (12) | O4'—C4'—C5' | 109.11 (14) |
N8—C7—H7A | 127.3 | O4'—C4'—C3' | 104.53 (11) |
C5—C7—H7A | 127.3 | C5'—C4'—C3' | 115.30 (14) |
C7—N8—N9 | 114.85 (11) | O4'—C4'—H4' | 109.2 |
C7—N8—C1' | 128.26 (12) | C5'—C4'—H4' | 109.2 |
N9—N8—C1' | 116.86 (11) | C3'—C4'—H4' | 109.2 |
C4—N9—N8 | 103.00 (11) | C1'—O4'—C4' | 109.86 (12) |
O4'—C1'—N8 | 108.43 (11) | O5'—C5'—C4' | 109.71 (15) |
O4'—C1'—C2' | 107.21 (11) | O5'—C5'—H5'1 | 109.7 |
N8—C1'—C2' | 111.94 (12) | C4'—C5'—H5'1 | 109.7 |
O4'—C1'—H1' | 109.7 | O5'—C5'—H5'2 | 109.7 |
N8—C1'—H1' | 109.7 | C4'—C5'—H5'2 | 109.7 |
C2'—C1'—H1' | 109.7 | H5'1—C5'—H5'2 | 108.2 |
O2'—C2'—C3' | 107.26 (12) | C5'—O5'—H5' | 109.5 |
O2'—C2'—C1' | 110.31 (14) | H10A—O10—H10B | 118 (4) |
C3'—C2'—C1' | 101.25 (12) | ||
C6—N1—C2—N3 | 1.5 (3) | N9—N8—C1'—O4' | −161.81 (14) |
N1—C2—N3—C4 | −1.5 (3) | C7—N8—C1'—C2' | −97.96 (19) |
C2—N3—C4—N9 | 179.22 (18) | N9—N8—C1'—C2' | 80.13 (17) |
C2—N3—C4—C5 | 0.3 (2) | O4'—C1'—C2'—O2' | 87.49 (14) |
N9—C4—C5—C7 | −0.3 (2) | N8—C1'—C2'—O2' | −153.72 (12) |
N3—C4—C5—C7 | 178.70 (17) | O4'—C1'—C2'—C3' | −25.86 (14) |
N9—C4—C5—C6 | −178.41 (16) | N8—C1'—C2'—C3' | 92.93 (13) |
N3—C4—C5—C6 | 0.6 (2) | C3'—C2'—O2'—C2'O | −165.21 (18) |
C2—N1—C6—N6 | −178.91 (18) | C1'—C2'—O2'—C2'O | 85.3 (2) |
C2—N1—C6—C5 | −0.3 (2) | O2'—C2'—C3'—O3' | 45.1 (2) |
C7—C5—C6—N6 | 0.6 (3) | C1'—C2'—C3'—O3' | 160.77 (15) |
C4—C5—C6—N6 | 177.96 (18) | O2'—C2'—C3'—C4' | −78.21 (15) |
C7—C5—C6—N1 | −177.92 (19) | C1'—C2'—C3'—C4' | 37.41 (13) |
C4—C5—C6—N1 | −0.6 (2) | O3'—C3'—C4'—O4' | −159.20 (13) |
C4—C5—C7—N8 | 0.35 (18) | C2'—C3'—C4'—O4' | −37.00 (14) |
C6—C5—C7—N8 | 177.9 (2) | O3'—C3'—C4'—C5' | 81.03 (18) |
C5—C7—N8—N9 | −0.3 (2) | C2'—C3'—C4'—C5' | −156.78 (13) |
C5—C7—N8—C1' | 177.80 (15) | N8—C1'—O4'—C4' | −118.13 (13) |
N3—C4—N9—N8 | −178.88 (17) | C2'—C1'—O4'—C4' | 2.90 (15) |
C5—C4—N9—N8 | 0.11 (19) | C5'—C4'—O4'—C1' | 145.51 (13) |
C7—N8—N9—C4 | 0.1 (2) | C3'—C4'—O4'—C1' | 21.66 (15) |
C1'—N8—N9—C4 | −178.21 (14) | O4'—C4'—C5'—O5' | 65.55 (16) |
C7—N8—C1'—O4' | 20.1 (2) | C3'—C4'—C5'—O5' | −177.23 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···N1i | 0.86 | 2.12 | 2.964 (2) | 169 |
N6—H6B···O10ii | 0.86 | 2.10 | 2.927 (2) | 161 |
O3′—H3′···O10 | 0.81 (1) | 2.38 (5) | 2.724 (3) | 107 (4) |
O5′—H5′···N3iii | 0.82 | 1.95 | 2.756 (2) | 170 |
O10—H10A···O10iv | 0.96 (1) | 2.61 (4) | 3.125 (5) | 115 (3) |
O10—H10B···O5′v | 0.97 (4) | 1.90 (4) | 2.852 (3) | 169 (4) |
Symmetry codes: (i) −x+1, y, −z+1; (ii) −x+1/2, y+1/2, −z+2; (iii) x, y, z+1; (iv) −x, y, −z+2; (v) x, y−1, z. |
Experimental details
Crystal data | |
Chemical formula | C11H15N5O4·H2O |
Mr | 299.30 |
Crystal system, space group | Monoclinic, C2 |
Temperature (K) | 293 |
a, b, c (Å) | 17.263 (2), 7.5673 (7), 10.4757 (8) |
β (°) | 93.128 (8) |
V (Å3) | 1366.4 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.54 × 0.4 × 0.3 |
Data collection | |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2/s(I)] reflections | 2836, 2318, 2225 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.725 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.108, 1.00 |
No. of reflections | 2318 |
No. of parameters | 201 |
No. of restraints | 4 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.29, −0.16 |
Computer programs: XSCANS (Siemens, 1996), XSCANS, SHELXTL (Sheldrick, 1997), SHELXTL and PLATON (Spek, 1999).
N8—N9 | 1.3555 (15) | C2'—O2' | 1.4086 (17) |
N8—C1' | 1.4718 (17) | O2'—C2'O | 1.420 (2) |
N6—C6—N1 | 118.58 (13) | C7—N8—C1' | 128.26 (12) |
N6—C6—C5 | 123.34 (13) | N9—N8—C1' | 116.86 (11) |
C7—N8—N9 | 114.85 (11) | C2'—O2'—C2'O | 113.74 (13) |
C2—N1—C6—N6 | −178.91 (18) | N9—N8—C1'—C2' | 80.13 (17) |
C7—C5—C6—N6 | 0.6 (3) | C1'—C2'—O2'—C2'O | 85.3 (2) |
C7—N8—C1'—O4' | 20.1 (2) | O4'—C4'—C5'—O5' | 65.55 (16) |
N9—N8—C1'—O4' | −161.81 (14) | C3'—C4'—C5'—O5' | −177.23 (13) |
C7—N8—C1'—C2' | −97.96 (19) |
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···N1i | 0.86 | 2.12 | 2.964 (2) | 169 |
N6—H6B···O10ii | 0.86 | 2.10 | 2.927 (2) | 161 |
O3'—H3'···O10 | 0.81 (1) | 2.38 (5) | 2.724 (3) | 107 (4) |
O5'—H5'···N3iii | 0.82 | 1.95 | 2.756 (2) | 170 |
O10—H10A···O10iv | 0.96 (1) | 2.61 (4) | 3.125 (5) | 115 (3) |
O10—H10B···O5'v | 0.97 (4) | 1.90 (4) | 2.852 (3) | 169 (4) |
Symmetry codes: (i) −x+1, y, −z+1; (ii) −x+1/2, y+1/2, −z+2; (iii) x, y, z+1; (iv) −x, y, −z+2; (v) x, y−1, z. |
Subscribe to Acta Crystallographica Section C: Structural Chemistry
The full text of this article is available to subscribers to the journal.
- Information on subscribing
- Sample issue
- Purchase subscription
- Reduced-price subscriptions
- If you have already subscribed, you may need to register
Considerable efforts have been focused on the study of nucleobase analogues that fulfil the concepts of an ideal universal base. A universal base should be capable of substituting any of the four natural occurring bases without discrimination and significant destabilization of the DNA-duplex. Such bases would be of great use in both mutagenesis and recombinant DNA-experiments (Loakes, 2001). The N8-2'-deoxyribonucleosides of 8-aza-7-deazaadenine and 2-amino-8-aza-7-deazaadenine show the properties of an universal nucleosides due to their ambiguous base pairing when incorporated into oligonucleotide duplexes opposite to the four canonical DNA-constituents (Seela & Debelak, 2000; Seela et al., 2000; He & Seela, 2002, 2003).
The 2'-O-methyl modification of ribonucleosides is a natural variety of the canonical RNA-constituents and is part of the minor components found in tRNA. Synthetically obtained 2'-O-methyloligoribonucleotides are of great use in antisense technology because of their enhanced RNase and DNase resistance and their increased thermal stability of their duplexes and triplexes (Sproat et al., 1989; Oberhauser & Wagner, 1992; Goodchild, 1992). In order to design an artifical nucleoside that joins the concept of a universal base and the properties of a highly enzymatically resistant DNA/RNA building block into one molecule, 4-amino-2-(2-O-methyl-β-D-ribofuranosyl)-2H- pyrazolo[3,4-d]pyrimidine [8-aza-7-deazaadenine N8-(2'-O-methyl-ribofuranoside); purine numbering is used throughout the paper], (I), was synthesized (Leonard et al., 2005).
The single-crystal X-ray structure of (I) is described here. The three-dimensional structure of (I) is shown in Fig. 1 and selected geometric parameters are summarized in Table 1.
For the canonical ribonucleosides the orientation of the base relative to the sugar (syn/anti) is defined by the torsion angle χ (O4'—C1'—N9—C4) (purine numbering; IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). For (I), this nomenclature is, however, not suitable. According to Seela & Debelak (2000), the conformation of the N-glycosylic bond is defined as O4'—C1'—N8—C7. The nucleoside is in the anti conformation when the distance between atoms H1' and H7 is at a minimum and syn when at a maximum. In the crystal structure of (I), the torsion angle of the glycosylic bond is χ = 20.1 (2)°, confirming syn conformation. Similar values were observed for the crystal structures of 4-nitro-2-(β-D-ribofuranosyl)-2H-indazole, (II) (type 2; Seela et al., 2004), and 2-(2-deoxy-β-D-erythro-furanosyl)-2H-pyrazolo[3,4-d]pyrimidine, (III) (He et al., 2002). The length of the N-glycosylic bond is 1.472 (2) Å, which is almost identical to that of (II) (type 2; Seela et al., 2004).
Owing to the stabilizing effect of the hydroxy group in the 2' position of the ribose ring, the predominant conformation observed for the ribofuranosyl moiety is the north conformation (C3'-endo). In contrast, both the C2'-endo (south) conformation (Hingerty et al., 1977) and the C3'-endo (north) conformation (Prusiner & Sundaralingam, 1976) have been reported for 2'-O-methylated ribonucleosides. The 2-O-methylribofuranose moiety of (I) exhibits a pseudorotation phase angle, P, of 14.3 (1)° and an amplitude, τm, of 39.6 (1)° (Rao et al., 1981), indicating that the sugar is in the N conformation. The C3'-endo (3T2) sugar puckering of (I) is consistent with the conformation found for unmodified ribonucleosides. This type of sugar conformation has also been reported for (II) (type 2; Seela et al., 2004) and 2'-O-methyladenosine (IV) (molecule A; Prusiner & Sundaralingam, 1976).
The conformation of the exocyclic C4'—C5' bond is -ap (trans) with a C3'—C4'—C5'—O5' torsion angle of γ = −177.23 (13)°. A similar value has also been found for the structures of (II) (type 2) [γ = −176.1 (5)°; Seela et al., 2004], whereas a +sc (+gauche) (γ = 48.7° for molecule A) and +ap (trans) (γ = 179.3° for molecule B) conformation about the C4'—C5' bond has been observed for 2'-O-methyladenosine, (IV).
Another parameter of interest is the conformation of the methoxy group. In (I), the methoxy group adopts a +sc conformation [C1'—C2'—O2'—C2'O = 85.3 (2)°]. In contrast to this, torsion angles with a +ac conformation have been found for the crystal structures of (IV) (Prusiner & Sundaralingam, 1976).
The heterocyclic ring of (I) is nearly planar, the r.m.s. deviation of the ring atoms N1/C2/N3/C4/C5/C7/N8/N9 from the least-squares plane being 0.0087 Å, with a maximum deviation of −0.017 (2) Å for atom C5. The exocyclic groups lie on different sides of the plane. Atom N6 of the amino group is situated 0.037 (3) Å above and atom C1' of the sugar moiety lies −0.015 (2) Å below this plane. Compound (I) forms a 1:1 complex with water, which is stabilized by hydrogen bonds.
In the crystalline state, the ribonucleoside molecules form a layered three-dimensional network consisting of alternating layers (Fig. 2), with the base moieties stacked head to head. The water molecules are situated between the ribonucleotide layers and connect the 2'-O-methylribonucleosides of adjacent layers via hydrogen bonding (Table 2 and Fig. 2). The water molecules act as hydrogen acceptors (O10), forming bifurcated hydrogen bonds with the H3'/O3' and N6'/H6' groups, and as donors (H10). Furthermore, intermolecular hydrogen bonds are formed between neighbouring nucleobases N6—H6A···N1 and the sugar moieties of the adjacent molecules O5'—H5'···N3 (Table 2).