In the title compound [systematic name: 7-(2-deoxy-β-
D-
erythro-pentofuranosyl)-2-fluoro-7
H-pyrrolo[2,3-
d]pyrimidin-2-amine], C
11H
13FN
4O
3, the conformation of the N-glycosylic bond is between
anti and high-
anti [χ = −110.2 (3)°]. The 2′-deoxyribofuranosyl unit adopts the
N-type sugar pucker (
4T3), with
P = 40.3° and τ
m = 39.2°. The orientation of the exocyclic C4′—C5′ bond is −
ap (
trans), with a torsion angle γ = −168.39 (18)°. The nucleobases are arranged head-to-head. The crystal structure is stabilized by four intermolecular hydrogen bonds of types N—H
N, N—H
O and O—H
O.
Supporting information
CCDC reference: 638318
Compound (III) was synthesized as described by Peng et al. (2006) and
crystallized from MeOH (m.p. 476 K). For the diffraction experiment, a
single-crystal was fixed at the top of a Lindemann capillary with epoxy resin.
In the absence of suitable anomalous scattering, Friedel equivalents could not
be used to determine the absolute structure. Refinement of the Flack (1983)
parameter led to an inconclusive value (Flack & Bernardinelli, 2000)
[0.1 (13)]. Therefore, Friedel equivalents (440) were merged before the final
refinement. The known configuration of the parent molecule was used to define
the enantiomer employed in the refined model. All H atoms were found in a
difference Fourier synthesis. In order to maximize the data/parameter ratio, H
atoms were placed in geometrically idealized positions [C—H = 0.93–0.98 Å
and N—H 0.86 Å (AFIX 93)] and constrained to ride on their parent atoms
[Uiso(H) = 1.2Ueq(C,N)]. The OH groups were refined
as rigid groups allowed to rotate but not tip [AFIX 147; O—H = 0.82 Å and
Uiso(H) = 1.5Ueq(O)].
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).
7-(2-deoxy-
β-
D-
erythro-pentofuranosyl)-
2-fluoro-7
H-pyrrolo[2,3-
d]pyrimidin-2-amine
top
Crystal data top
C11H13FN4O3 | F(000) = 560 |
Mr = 268.25 | Dx = 1.490 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 50 reflections |
a = 5.5515 (8) Å | θ = 2.4–14.9° |
b = 12.6547 (12) Å | µ = 0.12 mm−1 |
c = 17.0171 (19) Å | T = 293 K |
V = 1195.5 (2) Å3 | Plate, colourless |
Z = 4 | 0.5 × 0.3 × 0.3 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.032 |
Radiation source: fine-focus sealed tube | θmax = 29.0°, θmin = 2.4° |
Graphite monochromator | h = −1→7 |
2θ/ω scans | k = −17→1 |
2481 measured reflections | l = −23→1 |
1846 independent reflections | 3 standard reflections every 97 reflections |
1586 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.042 | w = 1/[σ2(Fo2) + (0.061P)2 + 0.1652P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.115 | (Δ/σ)max < 0.001 |
S = 1.04 | Δρmax = 0.18 e Å−3 |
1846 reflections | Δρmin = −0.22 e Å−3 |
175 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.016 (3) |
Primary atom site location: structure-invariant direct methods | Absolute structure: established on the basis of the previously
known absolute configuration of the molecule |
Secondary atom site location: difference Fourier map | |
Crystal data top
C11H13FN4O3 | V = 1195.5 (2) Å3 |
Mr = 268.25 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.5515 (8) Å | µ = 0.12 mm−1 |
b = 12.6547 (12) Å | T = 293 K |
c = 17.0171 (19) Å | 0.5 × 0.3 × 0.3 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.032 |
2481 measured reflections | 3 standard reflections every 97 reflections |
1846 independent reflections | intensity decay: none |
1586 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.115 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.18 e Å−3 |
1846 reflections | Δρmin = −0.22 e Å−3 |
175 parameters | Absolute structure: established on the basis of the previously
known absolute configuration of the molecule |
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 | 1.0271 (5) | 0.89211 (15) | 0.74187 (12) | 0.0476 (5) | |
C2 | 1.0734 (6) | 0.7907 (2) | 0.74930 (16) | 0.0492 (7) | |
F2 | 1.2514 (4) | 0.76934 (13) | 0.80207 (12) | 0.0803 (8) | |
N3 | 0.9844 (5) | 0.70558 (14) | 0.71709 (11) | 0.0443 (5) | |
C4 | 0.8137 (5) | 0.73341 (16) | 0.66410 (12) | 0.0366 (5) | |
C5 | 0.7403 (5) | 0.83631 (16) | 0.64632 (12) | 0.0370 (5) | |
C6 | 0.8525 (5) | 0.91714 (16) | 0.69033 (13) | 0.0367 (5) | |
N6 | 0.7931 (5) | 1.01961 (14) | 0.68420 (12) | 0.0439 (5) | |
H6A | 0.8658 | 1.0660 | 0.7126 | 0.053* | |
H6B | 0.6824 | 1.0389 | 0.6519 | 0.053* | |
C7 | 0.5593 (5) | 0.82845 (19) | 0.58714 (14) | 0.0446 (6) | |
H7 | 0.4786 | 0.8842 | 0.5632 | 0.054* | |
C8 | 0.5273 (6) | 0.72416 (19) | 0.57248 (15) | 0.0482 (6) | |
H8 | 0.4183 | 0.6964 | 0.5365 | 0.058* | |
N9 | 0.6824 (4) | 0.66466 (14) | 0.61944 (11) | 0.0411 (5) | |
C1' | 0.6930 (5) | 0.55026 (16) | 0.62439 (13) | 0.0383 (5) | |
H1' | 0.7902 | 0.5300 | 0.6700 | 0.046* | |
C2' | 0.4482 (5) | 0.49669 (18) | 0.62964 (15) | 0.0455 (6) | |
H2'1 | 0.3216 | 0.5483 | 0.6382 | 0.055* | |
H2'2 | 0.4452 | 0.4456 | 0.6721 | 0.055* | |
C3' | 0.4173 (4) | 0.44234 (16) | 0.55042 (14) | 0.0375 (5) | |
H3'1 | 0.3436 | 0.4906 | 0.5123 | 0.045* | |
O3' | 0.2834 (3) | 0.34664 (13) | 0.55535 (13) | 0.0523 (5) | |
H3' | 0.1755 | 0.3472 | 0.5224 | 0.078* | |
C4' | 0.6772 (4) | 0.41982 (15) | 0.52841 (13) | 0.0327 (4) | |
H4' | 0.7339 | 0.3580 | 0.5578 | 0.039* | |
C5' | 0.7188 (5) | 0.40208 (18) | 0.44208 (13) | 0.0412 (5) | |
H5'1 | 0.5989 | 0.3531 | 0.4223 | 0.049* | |
H5'2 | 0.6989 | 0.4685 | 0.4143 | 0.049* | |
O5' | 0.9538 (4) | 0.36091 (14) | 0.42630 (11) | 0.0505 (5) | |
H5' | 0.9433 | 0.2983 | 0.4145 | 0.076* | |
O4' | 0.8063 (3) | 0.51118 (12) | 0.55392 (9) | 0.0413 (4) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0639 (14) | 0.0319 (9) | 0.0471 (10) | −0.0044 (10) | −0.0149 (11) | −0.0046 (8) |
C2 | 0.0607 (17) | 0.0374 (11) | 0.0494 (12) | 0.0018 (13) | −0.0207 (13) | −0.0009 (10) |
F2 | 0.1040 (19) | 0.0452 (8) | 0.0916 (13) | 0.0015 (10) | −0.0657 (13) | −0.0053 (9) |
N3 | 0.0566 (13) | 0.0302 (8) | 0.0461 (10) | 0.0021 (9) | −0.0173 (10) | −0.0021 (8) |
C4 | 0.0443 (12) | 0.0295 (9) | 0.0361 (9) | 0.0013 (10) | −0.0053 (10) | −0.0036 (8) |
C5 | 0.0473 (13) | 0.0302 (9) | 0.0334 (9) | 0.0031 (10) | −0.0021 (9) | 0.0011 (8) |
C6 | 0.0459 (12) | 0.0294 (9) | 0.0348 (9) | −0.0009 (10) | 0.0044 (10) | 0.0005 (8) |
N6 | 0.0608 (13) | 0.0270 (8) | 0.0439 (9) | −0.0016 (10) | −0.0026 (11) | −0.0015 (8) |
C7 | 0.0517 (14) | 0.0362 (10) | 0.0459 (11) | 0.0076 (11) | −0.0104 (12) | 0.0001 (10) |
C8 | 0.0555 (15) | 0.0407 (11) | 0.0482 (12) | 0.0060 (12) | −0.0192 (12) | −0.0034 (10) |
N9 | 0.0511 (11) | 0.0298 (8) | 0.0424 (9) | 0.0033 (9) | −0.0135 (10) | −0.0056 (7) |
C1' | 0.0466 (12) | 0.0290 (9) | 0.0392 (10) | 0.0002 (10) | −0.0046 (11) | −0.0042 (9) |
C2' | 0.0472 (13) | 0.0379 (11) | 0.0515 (12) | 0.0012 (11) | 0.0085 (12) | −0.0060 (10) |
C3' | 0.0320 (10) | 0.0273 (9) | 0.0531 (12) | 0.0001 (9) | −0.0013 (10) | −0.0030 (9) |
O3' | 0.0376 (8) | 0.0371 (8) | 0.0822 (13) | −0.0086 (8) | −0.0049 (10) | −0.0034 (9) |
C4' | 0.0329 (10) | 0.0249 (8) | 0.0402 (10) | 0.0017 (9) | −0.0028 (9) | −0.0023 (8) |
C5' | 0.0466 (12) | 0.0360 (10) | 0.0409 (10) | 0.0035 (10) | −0.0045 (11) | −0.0046 (9) |
O5' | 0.0496 (10) | 0.0466 (9) | 0.0554 (10) | 0.0006 (9) | 0.0122 (9) | −0.0146 (8) |
O4' | 0.0384 (8) | 0.0374 (8) | 0.0481 (8) | −0.0083 (7) | 0.0033 (8) | −0.0127 (7) |
Geometric parameters (Å, º) top
N1—C2 | 1.315 (3) | C1'—O4' | 1.442 (3) |
N1—C6 | 1.345 (3) | C1'—C2' | 1.521 (4) |
C2—N3 | 1.305 (3) | C1'—H1' | 0.9800 |
C2—F2 | 1.362 (3) | C2'—C3' | 1.523 (3) |
N3—C4 | 1.355 (3) | C2'—H2'1 | 0.9700 |
C4—N9 | 1.366 (3) | C2'—H2'2 | 0.9700 |
C4—C5 | 1.398 (3) | C3'—O3' | 1.424 (3) |
C5—C6 | 1.413 (3) | C3'—C4' | 1.517 (3) |
C5—C7 | 1.426 (3) | C3'—H3'1 | 0.9800 |
C6—N6 | 1.342 (3) | O3'—H3' | 0.8200 |
N6—H6A | 0.8600 | C4'—O4' | 1.428 (2) |
N6—H6B | 0.8600 | C4'—C5' | 1.504 (3) |
C7—C8 | 1.355 (3) | C4'—H4' | 0.9800 |
C7—H7 | 0.9300 | C5'—O5' | 1.430 (3) |
C8—N9 | 1.395 (3) | C5'—H5'1 | 0.9700 |
C8—H8 | 0.9300 | C5'—H5'2 | 0.9700 |
N9—C1' | 1.451 (3) | O5'—H5' | 0.8200 |
| | | |
C2—N1—C6 | 115.7 (2) | N9—C1'—H1' | 109.2 |
N3—C2—N1 | 133.7 (3) | C2'—C1'—H1' | 109.2 |
N3—C2—F2 | 112.8 (2) | C1'—C2'—C3' | 104.5 (2) |
N1—C2—F2 | 113.5 (2) | C1'—C2'—H2'1 | 110.9 |
C2—N3—C4 | 109.25 (19) | C3'—C2'—H2'1 | 110.9 |
N3—C4—N9 | 125.3 (2) | C1'—C2'—H2'2 | 110.9 |
N3—C4—C5 | 126.2 (2) | C3'—C2'—H2'2 | 110.9 |
N9—C4—C5 | 108.5 (2) | H2'1—C2'—H2'2 | 108.9 |
C4—C5—C6 | 115.5 (2) | O3'—C3'—C4' | 110.56 (17) |
C4—C5—C7 | 107.06 (19) | O3'—C3'—C2' | 113.0 (2) |
C6—C5—C7 | 137.4 (2) | C4'—C3'—C2' | 101.32 (18) |
N6—C6—N1 | 117.1 (2) | O3'—C3'—H3'1 | 110.5 |
N6—C6—C5 | 123.4 (2) | C4'—C3'—H3'1 | 110.5 |
N1—C6—C5 | 119.5 (2) | C2'—C3'—H3'1 | 110.5 |
C6—N6—H6A | 120.0 | C3'—O3'—H3' | 109.5 |
C6—N6—H6B | 120.0 | O4'—C4'—C5' | 109.93 (18) |
H6A—N6—H6B | 120.0 | O4'—C4'—C3' | 104.48 (16) |
C8—C7—C5 | 106.9 (2) | C5'—C4'—C3' | 114.5 (2) |
C8—C7—H7 | 126.6 | O4'—C4'—H4' | 109.2 |
C5—C7—H7 | 126.6 | C5'—C4'—H4' | 109.2 |
C7—C8—N9 | 109.8 (2) | C3'—C4'—H4' | 109.2 |
C7—C8—H8 | 125.1 | O5'—C5'—C4' | 112.21 (19) |
N9—C8—H8 | 125.1 | O5'—C5'—H5'1 | 109.2 |
C4—N9—C8 | 107.72 (18) | C4'—C5'—H5'1 | 109.2 |
C4—N9—C1' | 125.5 (2) | O5'—C5'—H5'2 | 109.2 |
C8—N9—C1' | 126.6 (2) | C4'—C5'—H5'2 | 109.2 |
O4'—C1'—N9 | 108.15 (19) | H5'1—C5'—H5'2 | 107.9 |
O4'—C1'—C2' | 106.60 (18) | C5'—O5'—H5' | 109.5 |
N9—C1'—C2' | 114.3 (2) | C4'—O4'—C1' | 108.16 (17) |
O4'—C1'—H1' | 109.2 | | |
| | | |
C6—N1—C2—N3 | −0.4 (5) | C5—C4—N9—C1' | −175.6 (2) |
C6—N1—C2—F2 | 180.0 (2) | C7—C8—N9—C4 | −0.1 (3) |
N1—C2—N3—C4 | 1.9 (5) | C7—C8—N9—C1' | 176.1 (3) |
F2—C2—N3—C4 | −178.4 (2) | C4—N9—C1'—O4' | −110.2 (3) |
C2—N3—C4—N9 | −179.8 (3) | C8—N9—C1'—O4' | 74.2 (3) |
C2—N3—C4—C5 | −0.5 (4) | C4—N9—C1'—C2' | 131.2 (3) |
N3—C4—C5—C6 | −2.0 (4) | C8—N9—C1'—C2' | −44.4 (4) |
N9—C4—C5—C6 | 177.4 (2) | O4'—C1'—C2'—C3' | −10.1 (2) |
N3—C4—C5—C7 | 179.5 (3) | N9—C1'—C2'—C3' | 109.3 (2) |
N9—C4—C5—C7 | −1.1 (3) | C1'—C2'—C3'—O3' | 147.47 (19) |
C2—N1—C6—N6 | 176.9 (3) | C1'—C2'—C3'—C4' | 29.2 (2) |
C2—N1—C6—C5 | −2.6 (4) | O3'—C3'—C4'—O4' | −158.81 (18) |
C4—C5—C6—N6 | −175.9 (2) | C2'—C3'—C4'—O4' | −38.8 (2) |
C7—C5—C6—N6 | 2.0 (5) | O3'—C3'—C4'—C5' | 80.9 (2) |
C4—C5—C6—N1 | 3.6 (3) | C2'—C3'—C4'—C5' | −159.07 (18) |
C7—C5—C6—N1 | −178.6 (3) | O4'—C4'—C5'—O5' | 74.4 (2) |
C4—C5—C7—C8 | 1.0 (3) | C3'—C4'—C5'—O5' | −168.39 (18) |
C6—C5—C7—C8 | −177.0 (3) | C5'—C4'—O4'—C1' | 157.37 (18) |
C5—C7—C8—N9 | −0.5 (3) | C3'—C4'—O4'—C1' | 34.0 (2) |
N3—C4—N9—C8 | −179.9 (3) | N9—C1'—O4'—C4' | −138.2 (2) |
C5—C4—N9—C8 | 0.7 (3) | C2'—C1'—O4'—C4' | −14.8 (2) |
N3—C4—N9—C1' | 3.8 (5) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···N3i | 0.86 | 2.29 | 3.144 (3) | 172 |
N6—H6B···O5′ii | 0.86 | 2.23 | 3.061 (3) | 162 |
O3′—H3′···O5′iii | 0.82 | 2.05 | 2.864 (3) | 169 |
O5′—H5′···O3′iv | 0.82 | 2.10 | 2.809 (3) | 145 |
Symmetry codes: (i) −x+2, y+1/2, −z+3/2; (ii) x−1/2, −y+3/2, −z+1; (iii) x−1, y, z; (iv) x+1/2, −y+1/2, −z+1. |
Experimental details
Crystal data |
Chemical formula | C11H13FN4O3 |
Mr | 268.25 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 5.5515 (8), 12.6547 (12), 17.0171 (19) |
V (Å3) | 1195.5 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.5 × 0.3 × 0.3 |
|
Data collection |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2481, 1846, 1586 |
Rint | 0.032 |
(sin θ/λ)max (Å−1) | 0.682 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.115, 1.04 |
No. of reflections | 1846 |
No. of parameters | 175 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.18, −0.22 |
Absolute structure | Established on the basis of the previously
known absolute configuration of the molecule |
Selected geometric parameters (Å, º) topN1—C2 | 1.315 (3) | C2—F2 | 1.362 (3) |
N1—C6 | 1.345 (3) | N3—C4 | 1.355 (3) |
C2—N3 | 1.305 (3) | N9—C1' | 1.451 (3) |
| | | |
N3—C2—F2 | 112.8 (2) | N6—C6—C5 | 123.4 (2) |
N1—C2—F2 | 113.5 (2) | C4—N9—C1' | 125.5 (2) |
N6—C6—N1 | 117.1 (2) | C8—N9—C1' | 126.6 (2) |
| | | |
C6—N1—C2—F2 | 180.0 (2) | O3'—C3'—C4'—C5' | 80.9 (2) |
F2—C2—N3—C4 | −178.4 (2) | O4'—C4'—C5'—O5' | 74.4 (2) |
C4—N9—C1'—O4' | −110.2 (3) | C3'—C4'—C5'—O5' | −168.39 (18) |
C8—N9—C1'—O4' | 74.2 (3) | C5'—C4'—O4'—C1' | 157.37 (18) |
C1'—C2'—C3'—C4' | 29.2 (2) | C3'—C4'—O4'—C1' | 34.0 (2) |
C2'—C3'—C4'—O4' | −38.8 (2) | C2'—C1'—O4'—C4' | −14.8 (2) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···N3i | 0.86 | 2.29 | 3.144 (3) | 171.7 |
N6—H6B···O5'ii | 0.86 | 2.23 | 3.061 (3) | 161.5 |
O3'—H3'···O5'iii | 0.82 | 2.05 | 2.864 (3) | 169.2 |
O5'—H5'···O3'iv | 0.82 | 2.10 | 2.809 (3) | 144.5 |
Symmetry codes: (i) −x+2, y+1/2, −z+3/2; (ii) x−1/2, −y+3/2, −z+1; (iii) x−1, y, z; (iv) x+1/2, −y+1/2, −z+1. |
Halogen-substituted analogues of nucleic acid components have become established as antiviral, antitumour and antifungal agents (Pankiewicz, 2000). An interesting family of this class of compounds is the haloadenine nucleosides, e.g. fludarabine, (Ia), cladribine (2-chloro-2'-deoxyadenosine), (IIa), clofarabine, (IIb), and 2'-deoxy-2-fluoroadenosine, (Ib) (Montgomery & Hewson, 1969; Montgomery, 1982; Bryson & Sorkin, 1993; Hassan et al., 2000). They are resistant to adenosine deaminase and effective in the treatment of indolent lymphoid malignancies, including chronic lymphocytic leukemia, hairy-cell leukemia, low-grade non-Hodgkin's lymphoma and acute myeloid leukaemia. Fludarabine and cladribine are used for the treatment of chronic lymphocytic leukaemia. However, the dose limitation of such drugs is imposed by cleavage resulting from rapid dephosphorylation, leading to a toxic 2-haloadenine with no anticancer activity (Struck et al., 1982). The introduction of fluorine at the 2'-position as in (IIb) confers resistance to phosphorolytic cleavage, which leads to lower toxicity (Montgomery et al., 1992).
As 7-deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides show resistance to the deamination caused by adenosine deaminase and cleavage by mammalian purine nucleoside phosphorylase, we became interested in 7-deaza-2-fluoroadenine nucleosides (purine numbering is used throughout the manuscript; IUPAC-IUB Joint Comission on Biochemical Nomenclature, 1983). Thus, 2'-deoxy-2-fluorotubercidin, (III), was prepared and its activity and base-pairing properties were studied (Peng et al., 2006). Similar to 2-haloadenine nucleosides (Montgomery & Hewson, 1970; Ramzaeva & Seela, 1994), (III) is a convertible nucleoside, allowing the attachment of functional groups to DNA for structural studies (Peng et al., 2006). The single-crystal X-ray analysis of compound (III) is described here.
The three-dimensional structure of (III) is shown in Fig. 1 and the selected geometric parameters are summarized in Table 1. The space group (P212121) is identical to that of the parent compound (IV) (Zabel et al., 1987) and the related compound (IIa) (Koellner et al., 1998).
The orientation of the base relative to the sugar (syn/anti) of purine nucleosides is defined by the torsion angle χ (O4'—C1'—N9—C4). For the `purine' 2'-deoxyribonucleosides, the preferred conformation around the N-glycosyl bond is usually in the anti range (Saenger, 1989; Sato, 1984). In the crystalline state of (III), the torsion angle of the glycosyl bond is between anti and high-anti with χ = -110.2 (3)°. This conformation is close to that of the parent compound 2'-deoxytubercidin, (IV) (χ = -104.4°; Zabel et al., 1987), but different from that of (IIa), which shows a syn conformation of the N-glycosylic bond [χ = 72.9 (3)°; Koellner et al., 1998)]. The glycosyl bond length (N9—C1') in (III) is 1.451 (3) Å, which is almost identical to those in (IV) [1.449 (2) Å] and (IIa) [1.458 (3) Å].
For (III), the phase angle of pseudorotation (P) is 40.3° and the maximum amplitude of puckering (τm) is 39.2°. This indicates that the sugar ring of (III) adopts an N conformation, with an unsymmetrical twist C3'-endo-C4'-exo (4T3) (Saenger, 1989). In the cases of (IV) and (IIa), the sugar ring conformation is S with P = 186.6 (2)° (3T2) for (IV) (Zabel et al., 1987) and 178.3° for (IIa) (Koellner et al., 1998). The conformation around the C4'—C5' bond of (III) is -ap (gauche, trans) with a torsion angle γ (C3'—C4'—C5'—O5') of -168.39 (18)°, whereas in (IV) and (IIa), the C4'—C5' bond shows a +ap (gauche, trans) conformation with γ = 179.6 (2)° for (IV) and 178.0 (2)° for (IIa).
The base moiety of compound (III) is essentially planar. The N3—C2 [1.305 (3) Å] and C2—N1 [1.315 (3) Å] bond lengths in (III) are shorter than those in (IV) (N3—C2 = 1.335 Å and C2—N1 = 1.333 Å). This might be caused by the strong electron-withdrawing effect of the 2-fluoro atom (pKa < 1.5) (Peng et al., 2006).
The structure of (III) is stabilized by hydrogen bonds leading to a three-dimensional network (Fig. 2 and Table 2). All four H atoms bonded to heteroatoms take part in the formation of the three-dimensional network (Table 2). The nucleobases are arranged head-to-head in a staircase-like fashion, in a pattern propagated by the a axis of the unit cell. Successive bases are nearly parallel with an interplanar spacing of approximately 3.894 Å, and are slipped in such a way that the C—F bond of the base at (x, y, z) projects on to the five-membered ring of the base at (1 + x, y, z). Thus, the average base pair distance is in the range of that of B-DNA (3.5 Å).