In the title regioisomeric nucleosides, alternatively called 1-(2-deoxy-β-D-erythro-furanosyl)-1H-pyrazolo[3,4-d]pyrimidine, C10H12N4O3, (II), and 2-(2-deoxy-β-D-erythro-furanosyl)-2H-pyrazolo[3,4-d]pyrimidine, C10H12N4O3, (III), the conformations of the glycosylic bonds are anti [−100.4 (2)° for (II) and 15.0 (2)° for (III)]. Both nucleosides adopt an S-type sugar pucker, which is C2′-endo-C3′-exo (2T3) for (II) and 3′-exo (between 3E and 4T3) for (III).
Supporting information
CCDC references: 197329; 197330
Nucleoside (II) (Seela & Steker, 1984) was prepared by the glycosylation
reaction of pyrazolo[3,4-d]pyrimidine with
2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-furanosyl
chloride (Hoffer, 1960), followed by deprotection of the sugar moiety (He &
Seela, 2002b); m.p.: 421 K, RF (silica gel thin-layer
chromatography): 0.22 (CH2Cl2/CH3OH, 9:1). Suitable crystals were grown
from a solution in methanol. Nucleoside (III) was obtained as the minor
product from the above glycosylation reaction followed by the deprotection of
the sugar moiety; m.p.: 427 K, RF (silica gel thin-layer
chromatography): 0.13 (CH2Cl2/CH3OH, 9:1). Suitable crystals were grown
from a solution in acetone.
In the absence of suitable anomalous scattering, Friedel equivalents could not
be use to determine the absotute structure. Refinement of the Flack (1983)
parameter led to inconclusive values (Flack & Bernardinelli, 2000) for this
parameter [-0.2 (16) for (II) and 0.4 (10) for (III)]. Therefore, the Friedel
equivalents [416 for (II) and 119 for (III)] 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-to-parameter
ratio, the H atoms bonded to C atoms were placed in geometrically idealized
positions (C—H = 0.93–0.98 Å) and constrained to ride on their parent
atoms. The hydroxy H atoms were initially placed in the difference map
positions, then geometrically idealized and constrained to ride on their
parent O atoms, although the chemically equivalent O—H bond lengths were
allowed to refine while being constrained to be equal. An overall isotropic
displacement parameter was refined for all H atoms.
For both compounds, 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.
(II) 1-(2-deoxy-
β-
D-
erythro-furanosyl)-1
H-pyrazolo[3,4-
d]pyrimidine
top
Crystal data top
C10H12N4O3 | Dx = 1.481 Mg m−3 |
Mr = 236.24 | Melting point: 421.15 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 40 reflections |
a = 6.9306 (8) Å | θ = 6.9–12.5° |
b = 11.1084 (15) Å | µ = 0.11 mm−1 |
c = 13.7591 (11) Å | T = 293 K |
V = 1059.3 (2) Å3 | Transparent needle, colourless |
Z = 4 | 0.58 × 0.28 × 0.28 mm |
F(000) = 496 | |
Data collection top
Bruker P4 diffractometer | Rint = 0.021 |
Radiation source: fine-focus sealed tube | θmax = 30.0°, θmin = 2.4° |
Graphite monochromator | h = −1→9 |
2θ/ω scans | k = −15→1 |
2375 measured reflections | l = −19→1 |
1784 independent reflections | 3 standard reflections every 97 reflections |
1474 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.042 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.105 | w = 1/[σ2(Fo2) + (0.0518P)2 + 0.1719P] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max < 0.001 |
1784 reflections | Δρmax = 0.21 e Å−3 |
164 parameters | Δρmin = −0.18 e Å−3 |
4 restraints | Extinction correction: SHELXTL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.023 (3) |
Crystal data top
C10H12N4O3 | V = 1059.3 (2) Å3 |
Mr = 236.24 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.9306 (8) Å | µ = 0.11 mm−1 |
b = 11.1084 (15) Å | T = 293 K |
c = 13.7591 (11) Å | 0.58 × 0.28 × 0.28 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.021 |
2375 measured reflections | 3 standard reflections every 97 reflections |
1784 independent reflections | intensity decay: none |
1474 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.042 | 4 restraints |
wR(F2) = 0.105 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.21 e Å−3 |
1784 reflections | Δρmin = −0.18 e Å−3 |
164 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
N1 | 0.8924 (3) | 0.39168 (15) | 0.57596 (12) | 0.0360 (4) | |
N2 | 1.0487 (3) | 0.40571 (19) | 0.51553 (14) | 0.0477 (5) | |
C3 | 1.0090 (4) | 0.4989 (2) | 0.45950 (16) | 0.0479 (6) | |
H3A | 1.0911 | 0.5288 | 0.4118 | 0.051 (2)* | |
C3A | 0.8249 (3) | 0.54761 (19) | 0.48135 (15) | 0.0379 (5) | |
C4 | 0.7003 (4) | 0.6378 (2) | 0.44932 (17) | 0.0463 (6) | |
H4A | 0.7374 | 0.6872 | 0.3981 | 0.051 (2)* | |
N5 | 0.5300 (3) | 0.65408 (18) | 0.49068 (15) | 0.0520 (5) | |
C6 | 0.4842 (4) | 0.5813 (2) | 0.56550 (18) | 0.0489 (6) | |
H6A | 0.3653 | 0.5956 | 0.5947 | 0.051 (2)* | |
N7 | 0.5877 (3) | 0.49145 (16) | 0.60313 (12) | 0.0379 (4) | |
C7A | 0.7571 (3) | 0.47689 (16) | 0.55842 (13) | 0.0310 (4) | |
C1' | 0.8940 (3) | 0.30189 (17) | 0.65227 (14) | 0.0342 (4) | |
H1'A | 0.7628 | 0.2935 | 0.6779 | 0.051 (2)* | |
C2' | 0.9654 (4) | 0.17831 (17) | 0.62058 (15) | 0.0412 (5) | |
H2'A | 1.0645 | 0.1845 | 0.5710 | 0.051 (2)* | |
H2'B | 0.8606 | 0.1286 | 0.5966 | 0.051 (2)* | |
O3' | 0.8964 (3) | 0.09209 (14) | 0.77947 (14) | 0.0558 (5) | |
H3'O | 0.877 (4) | 0.0222 (19) | 0.7689 (17) | 0.051 (2)* | |
C3' | 1.0469 (3) | 0.12955 (16) | 0.71604 (15) | 0.0366 (5) | |
H3'C | 1.1407 | 0.0651 | 0.7048 | 0.051 (2)* | |
C4' | 1.1416 (3) | 0.24088 (16) | 0.75843 (13) | 0.0323 (4) | |
H4' | 1.1428 | 0.2349 | 0.8295 | 0.051 (2)* | |
O4' | 1.0180 (3) | 0.33941 (11) | 0.72936 (10) | 0.0393 (4) | |
C5' | 1.3446 (4) | 0.2612 (2) | 0.72202 (16) | 0.0451 (5) | |
H5'A | 1.4254 | 0.1936 | 0.7404 | 0.051 (2)* | |
H5'B | 1.3440 | 0.2668 | 0.6517 | 0.051 (2)* | |
O5' | 1.4201 (3) | 0.3684 (2) | 0.76204 (12) | 0.0683 (6) | |
H5'O | 1.483 (4) | 0.401 (2) | 0.7210 (16) | 0.051 (2)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0363 (9) | 0.0364 (8) | 0.0354 (8) | 0.0026 (8) | 0.0028 (8) | 0.0077 (7) |
N2 | 0.0410 (10) | 0.0561 (11) | 0.0461 (9) | 0.0032 (10) | 0.0103 (9) | 0.0122 (9) |
C3 | 0.0466 (13) | 0.0568 (13) | 0.0402 (10) | −0.0023 (12) | 0.0071 (11) | 0.0144 (10) |
C3A | 0.0445 (12) | 0.0370 (10) | 0.0323 (9) | −0.0062 (9) | −0.0047 (10) | 0.0029 (8) |
C4 | 0.0593 (15) | 0.0379 (10) | 0.0417 (11) | −0.0043 (11) | −0.0107 (11) | 0.0090 (10) |
N5 | 0.0586 (13) | 0.0423 (10) | 0.0551 (11) | 0.0082 (10) | −0.0069 (11) | 0.0093 (9) |
C6 | 0.0463 (13) | 0.0447 (11) | 0.0556 (13) | 0.0100 (11) | 0.0005 (13) | 0.0018 (11) |
N7 | 0.0386 (9) | 0.0349 (8) | 0.0402 (8) | 0.0008 (8) | 0.0014 (8) | 0.0011 (7) |
C7A | 0.0357 (10) | 0.0277 (8) | 0.0296 (8) | −0.0028 (8) | −0.0068 (8) | −0.0011 (8) |
C1' | 0.0375 (10) | 0.0291 (8) | 0.0361 (9) | 0.0008 (8) | −0.0006 (9) | 0.0046 (8) |
C2' | 0.0519 (13) | 0.0279 (9) | 0.0437 (10) | −0.0034 (10) | −0.0042 (10) | −0.0079 (8) |
O3' | 0.0634 (12) | 0.0287 (7) | 0.0754 (11) | −0.0061 (8) | 0.0228 (11) | 0.0080 (8) |
C3' | 0.0439 (11) | 0.0216 (7) | 0.0444 (10) | 0.0019 (8) | 0.0067 (10) | 0.0007 (8) |
C4' | 0.0419 (11) | 0.0253 (8) | 0.0297 (8) | 0.0037 (8) | 0.0016 (9) | 0.0029 (7) |
O4' | 0.0573 (10) | 0.0230 (6) | 0.0378 (7) | 0.0074 (7) | −0.0082 (8) | −0.0025 (5) |
C5' | 0.0461 (12) | 0.0483 (12) | 0.0408 (10) | −0.0065 (11) | 0.0039 (11) | −0.0028 (10) |
O5' | 0.0808 (14) | 0.0824 (13) | 0.0418 (8) | −0.0455 (12) | 0.0150 (10) | −0.0154 (9) |
Geometric parameters (Å, º) top
N1—C7A | 1.354 (3) | C1'—H1'A | 0.9800 |
N1—N2 | 1.374 (2) | C2'—C3' | 1.529 (3) |
N1—C1' | 1.448 (2) | C2'—H2'A | 0.9700 |
N2—C3 | 1.320 (3) | C2'—H2'B | 0.9700 |
C3—C3A | 1.418 (3) | O3'—C3' | 1.422 (3) |
C3—H3A | 0.9300 | O3'—H3'O | 0.80 (2) |
C3A—C4 | 1.394 (3) | C3'—C4' | 1.517 (3) |
C3A—C7A | 1.401 (3) | C3'—H3'C | 0.9800 |
C4—N5 | 1.323 (3) | C4'—O4' | 1.446 (2) |
C4—H4A | 0.9300 | C4'—C5' | 1.510 (3) |
N5—C6 | 1.347 (3) | C4'—H4' | 0.9800 |
C6—N7 | 1.334 (3) | C5'—O5' | 1.412 (3) |
C6—H6A | 0.9300 | C5'—H5'A | 0.9700 |
N7—C7A | 1.335 (3) | C5'—H5'B | 0.9700 |
C1'—O4' | 1.427 (2) | O5'—H5'O | 0.80 (2) |
C1'—C2' | 1.523 (3) | | |
| | | |
C7A—N1—N2 | 111.02 (16) | C1'—C2'—C3' | 101.15 (15) |
C7A—N1—C1' | 128.04 (18) | C1'—C2'—H2'A | 111.5 |
N2—N1—C1' | 120.69 (17) | C3'—C2'—H2'A | 111.5 |
C3—N2—N1 | 106.14 (19) | C1'—C2'—H2'B | 111.5 |
N2—C3—C3A | 111.3 (2) | C3'—C2'—H2'B | 111.5 |
N2—C3—H3A | 124.4 | H2'A—C2'—H2'B | 109.4 |
C3A—C3—H3A | 124.4 | C3'—O3'—H3'O | 107.1 (16) |
C4—C3A—C7A | 115.8 (2) | O3'—C3'—C4' | 108.66 (17) |
C4—C3A—C3 | 139.9 (2) | O3'—C3'—C2' | 111.1 (2) |
C7A—C3A—C3 | 104.37 (19) | C4'—C3'—C2' | 101.62 (15) |
N5—C4—C3A | 121.0 (2) | O3'—C3'—H3'C | 111.7 |
N5—C4—H4A | 119.5 | C4'—C3'—H3'C | 111.7 |
C3A—C4—H4A | 119.5 | C2'—C3'—H3'C | 111.7 |
C4—N5—C6 | 117.2 (2) | O4'—C4'—C5' | 110.30 (16) |
N7—C6—N5 | 128.3 (2) | O4'—C4'—C3' | 104.74 (16) |
N7—C6—H6A | 115.9 | C5'—C4'—C3' | 113.41 (17) |
N5—C6—H6A | 115.9 | O4'—C4'—H4' | 109.4 |
C6—N7—C7A | 112.62 (19) | C5'—C4'—H4' | 109.4 |
N7—C7A—N1 | 127.69 (18) | C3'—C4'—H4' | 109.4 |
N7—C7A—C3A | 125.15 (19) | C1'—O4'—C4' | 109.93 (14) |
N1—C7A—C3A | 107.15 (19) | O5'—C5'—C4' | 110.00 (19) |
O4'—C1'—N1 | 110.02 (16) | O5'—C5'—H5'A | 109.7 |
O4'—C1'—C2' | 106.30 (16) | C4'—C5'—H5'A | 109.7 |
N1—C1'—C2' | 114.57 (16) | O5'—C5'—H5'B | 109.7 |
O4'—C1'—H1'A | 108.6 | C4'—C5'—H5'B | 109.7 |
N1—C1'—H1'A | 108.6 | H5'A—C5'—H5'B | 108.2 |
C2'—C1'—H1'A | 108.6 | C5'—O5'—H5'O | 107.9 (16) |
| | | |
C7A—N1—N2—C3 | −0.8 (3) | C3—C3A—C7A—N1 | −1.9 (2) |
C1'—N1—N2—C3 | −175.5 (2) | C7A—N1—C1'—O4' | −100.4 (2) |
N1—N2—C3—C3A | −0.5 (3) | N2—N1—C1'—O4' | 73.3 (2) |
N2—C3—C3A—C4 | −177.2 (3) | C7A—N1—C1'—C2' | 139.9 (2) |
N2—C3—C3A—C7A | 1.5 (3) | N2—N1—C1'—C2' | −46.4 (3) |
C7A—C3A—C4—N5 | 0.4 (3) | O4'—C1'—C2'—C3' | 30.5 (2) |
C3—C3A—C4—N5 | 178.9 (3) | N1—C1'—C2'—C3' | 152.21 (19) |
C3A—C4—N5—C6 | 1.0 (3) | C1'—C2'—C3'—O3' | 76.1 (2) |
C4—N5—C6—N7 | −1.6 (4) | C1'—C2'—C3'—C4' | −39.3 (2) |
N5—C6—N7—C7A | 0.6 (3) | O3'—C3'—C4'—O4' | −82.19 (18) |
C6—N7—C7A—N1 | −177.3 (2) | C2'—C3'—C4'—O4' | 35.0 (2) |
C6—N7—C7A—C3A | 1.0 (3) | O3'—C3'—C4'—C5' | 157.48 (17) |
N2—N1—C7A—N7 | −179.71 (19) | C2'—C3'—C4'—C5' | −85.3 (2) |
C1'—N1—C7A—N7 | −5.5 (3) | N1—C1'—O4'—C4' | −133.65 (17) |
N2—N1—C7A—C3A | 1.8 (2) | C2'—C1'—O4'—C4' | −9.1 (2) |
C1'—N1—C7A—C3A | 176.0 (2) | C5'—C4'—O4'—C1' | 105.76 (19) |
C4—C3A—C7A—N7 | −1.4 (3) | C3'—C4'—O4'—C1' | −16.6 (2) |
C3—C3A—C7A—N7 | 179.51 (19) | O4'—C4'—C5'—O5' | 60.9 (2) |
C4—C3A—C7A—N1 | 177.12 (18) | C3'—C4'—C5'—O5' | 177.97 (18) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3′—H3′O···O4′i | 0.80 (2) | 2.16 (2) | 2.871 (2) | 149 (3) |
O5′—H5′O···N7ii | 0.80 (2) | 2.04 (2) | 2.828 (3) | 168 (3) |
Symmetry codes: (i) −x+2, y−1/2, −z+3/2; (ii) x+1, y, z. |
(III) 2-(2-deoxy-
β-
D-
erythro-furanosyl)-2
H-pyrazolo[3,4-
d]pyrimidine
top
Crystal data top
C10H12N4O3 | F(000) = 248 |
Mr = 236.24 | Dx = 1.514 Mg m−3 |
Monoclinic, P21 | Melting point: 427.15 K |
Hall symbol: P 2yb | Mo Kα radiation, λ = 0.71073 Å |
a = 4.9396 (7) Å | Cell parameters from 47 reflections |
b = 13.1528 (14) Å | θ = 4.5–16.1° |
c = 8.1780 (12) Å | µ = 0.12 mm−1 |
β = 102.772 (9)° | T = 293 K |
V = 518.17 (12) Å3 | Transparent block, yellow |
Z = 2 | 0.57 × 0.57 × 0.48 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.021 |
Radiation source: fine-focus sealed tube | θmax = 30.0°, θmin = 3.0° |
Graphite monochromator | h = −6→1 |
2θ/ω scans | k = −1→18 |
2202 measured reflections | l = −11→11 |
1562 independent reflections | 3 standard reflections every 97 reflections |
1524 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.033 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.092 | w = 1/[σ2(Fo2) + (0.0637P)2 + 0.0228P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max < 0.001 |
1562 reflections | Δρmax = 0.28 e Å−3 |
164 parameters | Δρmin = −0.20 e Å−3 |
51 restraints | Extinction correction: SHELXTL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.026 (9) |
Crystal data top
C10H12N4O3 | V = 518.17 (12) Å3 |
Mr = 236.24 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 4.9396 (7) Å | µ = 0.12 mm−1 |
b = 13.1528 (14) Å | T = 293 K |
c = 8.1780 (12) Å | 0.57 × 0.57 × 0.48 mm |
β = 102.772 (9)° | |
Data collection top
Bruker P4 diffractometer | Rint = 0.021 |
2202 measured reflections | 3 standard reflections every 97 reflections |
1562 independent reflections | intensity decay: none |
1524 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.033 | 51 restraints |
wR(F2) = 0.092 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.28 e Å−3 |
1562 reflections | Δρmin = −0.20 e Å−3 |
164 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
N1 | 0.5700 (3) | 0.34085 (10) | 0.75921 (16) | 0.0342 (3) | |
N2 | 0.5129 (3) | 0.44193 (10) | 0.74881 (15) | 0.0298 (3) | |
C3 | 0.6151 (3) | 0.49316 (12) | 0.63402 (17) | 0.0319 (3) | |
H3 | 0.5962 | 0.5621 | 0.6090 | 0.0445 (17)* | |
C3A | 0.7568 (3) | 0.42020 (12) | 0.55988 (17) | 0.0302 (3) | |
C4 | 0.9209 (3) | 0.41530 (13) | 0.43949 (18) | 0.0344 (3) | |
H4 | 0.9559 | 0.4739 | 0.3840 | 0.0445 (17)* | |
N5 | 1.0250 (3) | 0.32733 (12) | 0.40560 (17) | 0.0380 (3) | |
C6 | 0.9690 (4) | 0.24315 (15) | 0.4897 (2) | 0.0413 (4) | |
H6 | 1.0398 | 0.1821 | 0.4599 | 0.0445 (17)* | |
N7 | 0.8271 (3) | 0.23774 (12) | 0.60788 (18) | 0.0400 (3) | |
C7A | 0.7196 (3) | 0.32771 (11) | 0.64265 (17) | 0.0306 (3) | |
C1' | 0.3648 (3) | 0.48283 (11) | 0.87360 (17) | 0.0299 (3) | |
H1'C | 0.2016 | 0.4407 | 0.8748 | 0.0445 (17)* | |
C2' | 0.5555 (3) | 0.48418 (13) | 1.04885 (18) | 0.0344 (3) | |
H2'A | 0.5155 | 0.4278 | 1.1163 | 0.0445 (17)* | |
H2'B | 0.7494 | 0.4816 | 1.0430 | 0.0445 (17)* | |
C3' | 0.4834 (3) | 0.58572 (12) | 1.11851 (17) | 0.0315 (3) | |
H3'C | 0.6403 | 0.6130 | 1.2019 | 0.0445 (17)* | |
O3' | 0.2466 (3) | 0.57069 (10) | 1.18791 (17) | 0.0433 (3) | |
H3'O | 0.218 (4) | 0.6217 (14) | 1.244 (3) | 0.0445 (17)* | |
C4' | 0.4171 (3) | 0.65211 (11) | 0.96105 (17) | 0.0287 (3) | |
H4O' | 0.2865 | 0.7056 | 0.9758 | 0.0445 (17)* | |
O4' | 0.2806 (2) | 0.58275 (9) | 0.82936 (13) | 0.0330 (2) | |
C5' | 0.6703 (3) | 0.70013 (13) | 0.91727 (19) | 0.0337 (3) | |
H5'B | 0.7573 | 0.7469 | 1.0049 | 0.0445 (17)* | |
H5'C | 0.8043 | 0.6481 | 0.9062 | 0.0445 (17)* | |
O5' | 0.5824 (3) | 0.75256 (14) | 0.76418 (19) | 0.0530 (4) | |
H5'O | 0.717 (4) | 0.774 (2) | 0.727 (2) | 0.0445 (17)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0468 (7) | 0.0271 (6) | 0.0327 (6) | 0.0008 (5) | 0.0172 (5) | 0.0007 (4) |
N2 | 0.0364 (6) | 0.0274 (6) | 0.0274 (5) | −0.0008 (4) | 0.0106 (4) | −0.0012 (4) |
C3 | 0.0377 (6) | 0.0297 (6) | 0.0296 (6) | −0.0015 (5) | 0.0106 (5) | 0.0015 (5) |
C3A | 0.0346 (6) | 0.0302 (6) | 0.0264 (5) | −0.0025 (5) | 0.0079 (5) | 0.0012 (5) |
C4 | 0.0373 (7) | 0.0392 (8) | 0.0283 (6) | −0.0038 (6) | 0.0103 (5) | 0.0031 (5) |
N5 | 0.0401 (6) | 0.0449 (7) | 0.0322 (6) | 0.0011 (6) | 0.0150 (5) | −0.0008 (6) |
C6 | 0.0513 (9) | 0.0377 (8) | 0.0393 (7) | 0.0059 (7) | 0.0198 (7) | −0.0017 (6) |
N7 | 0.0561 (8) | 0.0321 (6) | 0.0364 (6) | 0.0043 (6) | 0.0201 (6) | 0.0009 (5) |
C7A | 0.0382 (6) | 0.0285 (6) | 0.0265 (6) | −0.0014 (5) | 0.0101 (5) | 0.0008 (5) |
C1' | 0.0324 (6) | 0.0294 (6) | 0.0295 (6) | −0.0010 (5) | 0.0102 (5) | −0.0028 (5) |
C2' | 0.0422 (7) | 0.0329 (6) | 0.0280 (6) | 0.0052 (6) | 0.0077 (5) | −0.0007 (5) |
C3' | 0.0359 (6) | 0.0317 (6) | 0.0287 (5) | −0.0036 (5) | 0.0108 (5) | −0.0041 (5) |
O3' | 0.0552 (7) | 0.0374 (6) | 0.0468 (6) | −0.0086 (5) | 0.0314 (5) | −0.0067 (5) |
C4' | 0.0272 (5) | 0.0291 (6) | 0.0316 (6) | 0.0000 (4) | 0.0107 (5) | −0.0028 (5) |
O4' | 0.0326 (5) | 0.0316 (5) | 0.0329 (4) | 0.0041 (4) | 0.0028 (4) | −0.0028 (4) |
C5' | 0.0288 (6) | 0.0370 (7) | 0.0378 (7) | −0.0023 (5) | 0.0127 (5) | 0.0017 (6) |
O5' | 0.0399 (6) | 0.0720 (11) | 0.0503 (8) | −0.0007 (7) | 0.0169 (5) | 0.0235 (7) |
Geometric parameters (Å, º) top
N1—C7A | 1.3402 (18) | C1'—H1'C | 0.9800 |
N1—N2 | 1.3579 (18) | C2'—C3' | 1.525 (2) |
N2—C3 | 1.3417 (18) | C2'—H2'A | 0.9700 |
N2—C1' | 1.4817 (18) | C2'—H2'B | 0.9700 |
C3—C3A | 1.402 (2) | C3'—O3' | 1.4227 (18) |
C3—H3 | 0.9300 | C3'—C4' | 1.530 (2) |
C3A—C4 | 1.4083 (19) | C3'—H3'C | 0.9800 |
C3A—C7A | 1.424 (2) | O3'—H3'O | 0.842 (15) |
C4—N5 | 1.320 (2) | C4'—O4' | 1.4579 (17) |
C4—H4 | 0.9300 | C4'—C5' | 1.513 (2) |
N5—C6 | 1.364 (2) | C4'—H4O' | 0.9800 |
C6—N7 | 1.315 (2) | C5'—O5' | 1.411 (2) |
C6—H6 | 0.9300 | C5'—H5'B | 0.9700 |
N7—C7A | 1.353 (2) | C5'—H5'C | 0.9700 |
C1'—O4' | 1.4017 (19) | O5'—H5'O | 0.842 (15) |
C1'—C2' | 1.531 (2) | | |
| | | |
C7A—N1—N2 | 102.79 (12) | C3'—C2'—C1' | 102.35 (12) |
C3—N2—N1 | 115.49 (12) | C3'—C2'—H2'A | 111.3 |
C3—N2—C1' | 128.25 (13) | C1'—C2'—H2'A | 111.3 |
N1—N2—C1' | 116.08 (12) | C3'—C2'—H2'B | 111.3 |
N2—C3—C3A | 105.07 (13) | C1'—C2'—H2'B | 111.3 |
N2—C3—H3 | 127.5 | H2'A—C2'—H2'B | 109.2 |
C3A—C3—H3 | 127.5 | O3'—C3'—C2' | 107.92 (13) |
C3—C3A—C4 | 138.86 (15) | O3'—C3'—C4' | 111.90 (13) |
C3—C3A—C7A | 104.48 (12) | C2'—C3'—C4' | 102.11 (11) |
C4—C3A—C7A | 116.62 (14) | O3'—C3'—H3'C | 111.5 |
N5—C4—C3A | 119.86 (15) | C2'—C3'—H3'C | 111.5 |
N5—C4—H4 | 120.1 | C4'—C3'—H3'C | 111.5 |
C3A—C4—H4 | 120.1 | C3'—O3'—H3'O | 110.9 (12) |
C4—N5—C6 | 118.28 (13) | O4'—C4'—C5' | 110.97 (11) |
N7—C6—N5 | 127.96 (16) | O4'—C4'—C3' | 104.04 (12) |
N7—C6—H6 | 116.0 | C5'—C4'—C3' | 113.76 (12) |
N5—C6—H6 | 116.0 | O4'—C4'—H4O' | 109.3 |
C6—N7—C7A | 113.88 (15) | C5'—C4'—H4O' | 109.3 |
N1—C7A—N7 | 124.48 (13) | C3'—C4'—H4O' | 109.3 |
N1—C7A—C3A | 112.17 (13) | C1'—O4'—C4' | 109.49 (10) |
N7—C7A—C3A | 123.34 (13) | O5'—C5'—C4' | 107.80 (12) |
O4'—C1'—N2 | 109.03 (11) | O5'—C5'—H5'B | 110.1 |
O4'—C1'—C2' | 108.47 (11) | C4'—C5'—H5'B | 110.1 |
N2—C1'—C2' | 110.72 (12) | O5'—C5'—H5'C | 110.1 |
O4'—C1'—H1'C | 109.5 | C4'—C5'—H5'C | 110.1 |
N2—C1'—H1'C | 109.5 | H5'B—C5'—H5'C | 108.5 |
C2'—C1'—H1'C | 109.5 | C5'—O5'—H5'O | 112.0 (12) |
| | | |
C7A—N1—N2—C3 | 0.14 (17) | C3—N2—C1'—O4' | 15.0 (2) |
C7A—N1—N2—C1' | −175.41 (12) | N1—N2—C1'—O4' | −170.15 (12) |
N1—N2—C3—C3A | −0.39 (17) | C3—N2—C1'—C2' | −104.29 (17) |
C1'—N2—C3—C3A | 174.52 (13) | N1—N2—C1'—C2' | 70.59 (16) |
N2—C3—C3A—C4 | −176.77 (17) | O4'—C1'—C2'—C3' | 19.55 (15) |
N2—C3—C3A—C7A | 0.44 (16) | N2—C1'—C2'—C3' | 139.15 (12) |
C3—C3A—C4—N5 | 178.72 (17) | C1'—C2'—C3'—O3' | 84.82 (15) |
C7A—C3A—C4—N5 | 1.7 (2) | C1'—C2'—C3'—C4' | −33.24 (15) |
C3A—C4—N5—C6 | 0.0 (2) | O3'—C3'—C4'—O4' | −79.14 (13) |
C4—N5—C6—N7 | −2.3 (3) | C2'—C3'—C4'—O4' | 36.04 (14) |
N5—C6—N7—C7A | 2.3 (3) | O3'—C3'—C4'—C5' | 159.99 (12) |
N2—N1—C7A—N7 | 179.37 (15) | C2'—C3'—C4'—C5' | −84.83 (15) |
N2—N1—C7A—C3A | 0.17 (17) | N2—C1'—O4'—C4' | −117.32 (12) |
C6—N7—C7A—N1 | −179.35 (16) | C2'—C1'—O4'—C4' | 3.33 (14) |
C6—N7—C7A—C3A | −0.2 (2) | C5'—C4'—O4'—C1' | 97.79 (14) |
C3—C3A—C7A—N1 | −0.40 (18) | C3'—C4'—O4'—C1' | −24.93 (14) |
C4—C3A—C7A—N1 | 177.55 (13) | O4'—C4'—C5'—O5' | 58.82 (17) |
C3—C3A—C7A—N7 | −179.60 (14) | C3'—C4'—C5'—O5' | 175.73 (13) |
C4—C3A—C7A—N7 | −1.7 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3′—H3′O···N7i | 0.84 (2) | 1.99 (2) | 2.832 (2) | 175 (2) |
O5′—H5′O···N5ii | 0.84 (2) | 1.97 (2) | 2.8011 (19) | 168 (2) |
Symmetry codes: (i) −x+1, y+1/2, −z+2; (ii) −x+2, y+1/2, −z+1. |
Experimental details
| (II) | (III) |
Crystal data |
Chemical formula | C10H12N4O3 | C10H12N4O3 |
Mr | 236.24 | 236.24 |
Crystal system, space group | Orthorhombic, P212121 | Monoclinic, P21 |
Temperature (K) | 293 | 293 |
a, b, c (Å) | 6.9306 (8), 11.1084 (15), 13.7591 (11) | 4.9396 (7), 13.1528 (14), 8.1780 (12) |
α, β, γ (°) | 90, 90, 90 | 90, 102.772 (9), 90 |
V (Å3) | 1059.3 (2) | 518.17 (12) |
Z | 4 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.11 | 0.12 |
Crystal size (mm) | 0.58 × 0.28 × 0.28 | 0.57 × 0.57 × 0.48 |
|
Data collection |
Diffractometer | Bruker P4 diffractometer | Bruker P4 diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2375, 1784, 1474 | 2202, 1562, 1524 |
Rint | 0.021 | 0.021 |
(sin θ/λ)max (Å−1) | 0.703 | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.105, 1.03 | 0.033, 0.092, 1.07 |
No. of reflections | 1784 | 1562 |
No. of parameters | 164 | 164 |
No. of restraints | 4 | 51 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.21, −0.18 | 0.28, −0.20 |
Selected geometric parameters (Å, º) for (II) topN1—C1' | 1.448 (2) | | |
| | | |
C7A—N1—C1' | 128.04 (18) | N2—N1—C1' | 120.69 (17) |
| | | |
C7A—N1—N2—C3 | −0.8 (3) | C1'—C2'—C3'—O3' | 76.1 (2) |
C1'—N1—N2—C3 | −175.5 (2) | C1'—C2'—C3'—C4' | −39.3 (2) |
C4—C3A—C7A—N7 | −1.4 (3) | C2'—C3'—C4'—O4' | 35.0 (2) |
C3—C3A—C7A—N7 | 179.51 (19) | O3'—C3'—C4'—C5' | 157.48 (17) |
C7A—N1—C1'—O4' | −100.4 (2) | N1—C1'—O4'—C4' | −133.65 (17) |
N2—N1—C1'—O4' | 73.3 (2) | C5'—C4'—O4'—C1' | 105.76 (19) |
C7A—N1—C1'—C2' | 139.9 (2) | C3'—C4'—O4'—C1' | −16.6 (2) |
O4'—C1'—C2'—C3' | 30.5 (2) | O4'—C4'—C5'—O5' | 60.9 (2) |
N1—C1'—C2'—C3' | 152.21 (19) | C3'—C4'—C5'—O5' | 177.97 (18) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3'—H3'O···O4'i | 0.80 (2) | 2.16 (2) | 2.871 (2) | 149 (3) |
O5'—H5'O···N7ii | 0.80 (2) | 2.04 (2) | 2.828 (3) | 168 (3) |
Symmetry codes: (i) −x+2, y−1/2, −z+3/2; (ii) x+1, y, z. |
Selected geometric parameters (Å, º) for (III) topN2—C1' | 1.4817 (18) | | |
| | | |
C7A—N1—N2 | 102.79 (12) | N1—N2—C1' | 116.08 (12) |
C3—N2—C1' | 128.25 (13) | | |
| | | |
C7A—N1—N2—C3 | 0.14 (17) | C1'—C2'—C3'—O3' | 84.82 (15) |
C7A—N1—N2—C1' | −175.41 (12) | C1'—C2'—C3'—C4' | −33.24 (15) |
C3—C3A—C7A—N7 | −179.60 (14) | C2'—C3'—C4'—O4' | 36.04 (14) |
C3—N2—C1'—O4' | 15.0 (2) | O3'—C3'—C4'—C5' | 159.99 (12) |
N1—N2—C1'—O4' | −170.15 (12) | C2'—C1'—O4'—C4' | 3.33 (14) |
N1—N2—C1'—C2' | 70.59 (16) | O4'—C4'—C5'—O5' | 58.82 (17) |
O4'—C1'—C2'—C3' | 19.55 (15) | C3'—C4'—C5'—O5' | 175.73 (13) |
N2—C1'—C2'—C3' | 139.15 (12) | | |
Hydrogen-bond geometry (Å, º) for (III) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3'—H3'O···N7i | 0.842 (15) | 1.992 (15) | 2.832 (2) | 175 (2) |
O5'—H5'O···N5ii | 0.842 (15) | 1.972 (15) | 2.8011 (19) | 168.0 (17) |
Symmetry codes: (i) −x+1, y+1/2, −z+2; (ii) −x+2, y+1/2, −z+1. |
During a search for more stable `dA-dT' base pairs, various 3-substituted pyrazolo[3,4-d]pyrimidine 2'-deoxyribonucleosides (7-substituted 8-aza-7-deazapurine 2'-deoxyribonucleosides) were studied as analogues of 2'-deoxyadenosine and were incorporated in oligonucleotides (systematic numbering is used throughout the paper). The interchange of the five-membered ring atoms and the presence of substituents (Br or I) on the 3-position in the modified purine bases exert an influence on the base-pair stability (Seela, Becher & Zulauf, 1999; He & Seela, 2002a). Common 2'-deoxyribonucleosides tend to adopt an anti conformation. 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 Commision on Biochemical Nomenclature, 1983). 2'-Deoxyadenosine shows an anti conformation, with a torsion angle χ (O4'—C1'—N1—C7a) of -165.1° (Sato, 1984), while that of pyrazolo[3,4-d]pyrimidin-4-amine 2'-deoxyribonucleoside (8-aza-7-deaza-2'-deoxyadenosine), (I), is between an anti and a high-anti conformation [χ = -106.3 (2)°; Seela, Zulauf et al., 1999]. Further substitution (Br or I) at the 3-position drives the conformation to high-anti [for the 3-bromo derivative, χ = -74.1 (4)°, while for the 3-iodo derivative, χ = -73.2 (4)°; Seela et al., 2000]. The steric and stereo-electronic effects of the nucleobases are supposed to be responsible for this change.
To the best of our knowledge, there is no reported crystal structure of a pyrazolo[3,4-d]pyrimidin-2-yl 2'-deoxyribonucleoside. Here, the X-ray crystallographic analyses of a pair of N1– and N2-glycosylated pyrazolo[3,4-d]pyrimidines, viz. (II) and (III), respectively, are described. Both nucleosides have the same β-D configuration. According to the systematic numbering for compound (II), the torsion angle χ is defined by O4'—C1'—N1—C7a. The definition for the N2-nucleoside, (II), follows that of other N2-nucleosides (Seela & Debelak, 2000). Here, the base is anti relative to the sugar moiety when the distance between H—C1' and H—C3 is minimal and syn when this distance is maximal, which is different from that of common nucleosides. Thus, the torsion angle is defined, in this case, by O4'—C1'—N2—C3.
From the crystal structure of compound (II) (Fig. 1), the conformation of the glycosylic bond is between the anti and the high-anti range, χ = -100.4 (2)°, which is very close to that of compound (I) (Seela, Zulauf et al., 1999). Compound (III) adopts an anti conformation, with χ = 15.0 (2)°. The glycosylic bond between atoms N2 and C1' of compound (III) is 0.034 Å longer than that between atoms N1 and C1' of compound (II).
Both nucleosides show an S-type sugar conformation, but with different ring puckering. The sugar conformation of nucleoisde (II) is C2'-endo-C3'-exo (2T3), with pseudo-rotation parameters (Rao et al., 1981) P = 185.6 (2)° and τm = 40.3 (1)°, while the sugar part of nucleoside (III) is 3'-exo (between 3E and 4T3), with P = 203.3 (1)° and τm = 37.0 (1)°. These two nucleosides have the same ap (g-) conformation about the C4'—C5' bond; the values of γ (C3'—C4'—C5'—O5') are 177.97 (18) and 175.73 (13)° for (II) and (III), respectively. This means that the base and the hydroxymethyl group undergo the same disrotatory motion so that the Coulomb repulsion between atoms N2 and O5' or between atoms N1 and O4' is minimized (Seela, Becher et al., 1999). Similarly, nucleoside (I) adopts the C2'-endo-C3'-exo-type (S-type) sugar puckering, but with an -ap conformation around the C4'—C5' bond [γ = -178.73 (16)°; Seela, Zulauf et al., 1999], while 2'-deoxyadenosine has a C3'-endo conformation (Sato, 1984). These results have an influence on the stability of oligonucleotide duplexes (He & Seela, 2002a).
The base moieties of (II) and (III) are nearly planar. The r.m.s. deviations of the ring atoms (N1/N2/C3/C3a/C4/N5/C6/N7/C7A) from their calculated least-squares planes are 0.018 and 0.013 Å, respectively, with the maximum deviations being 0.028 (2) (N1) and 0.019 (1) Å (C3A), respectively. Atom C1' is displaced from this plane by 0.033 (2) and 0.139 (1) Å in (II) and (III), respectively. The bases are strongly stacked in both crystal structures.
Structures (II) and (III), which differ only in the glycosylation positions (N1 versus N2), each form two different types of hydrogen bonds. Structure (II) is stabilized by intermolecular hydrogen bonds between O3'—H and O4'(2 - x, y - 1/2, 3/2 - z) of two sugar moieties and between O5'—OH of the sugar moiety and N7(1 + x, y, z) of an adjacent nucleobase unit. These interactions link the molecules into an infinite two-dimensional network in which the bases are stacked and tilted against each other. In contrast, structure (III) is stabilized by hydrogen bonds between the bases and the sugar units exclusively [O3'—H with N7(1 - x, 1/2 + y, 2 - z) and O5'—H with N5(2 - x, 1/2 + y, 1 - z)]. These interactions link the molecules into an infinite two-dimensional network, with piles of stacked bases tilted only slightly against each other.