organic compounds
(2R,3S,4R,5R)-5-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol
aJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang 330013, People's Republic of China
*Correspondence e-mail: ouyangruchun@aliyun.com
The title compound, C11H12FIN4O3, is composed of a 7-carbapurine moiety connected via an N atom to 2-deoxy-2-fluoro-β-D-ribose. The conformation about the N-glycosydic bond is −anti with χ = −129.0 (11)°. The glycosydic N—C bond length is 1.435 (14) Å. The sugar ring adopts an Nconformation with an unsymmetrical twist O-endo-C-exo (oT4). The conformation around the C—C bond is +sc, with a torsion angle of 53.0 (12)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming chains propagating along the a axis. These chains are linked via O—H⋯I and C—H⋯O hydrogen bonds, forming layers lying parallel to the c axis.
CCDC reference: 979239
Related literature
For the biological activity of fluorinated et al. (1971); Hertel et al. (1988); Watanabe et al. (1979). For puckering amplitudes, see: Saenger (1983). For sugar ring conformations, see: Evans & Boeyens (1989).
see: EtzoldExperimental
Crystal data
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Data collection: CrysAlis PRO (Agilent, 2013); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.
Supporting information
CCDC reference: 979239
10.1107/S1600536813034995/kp2461sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536813034995/kp2461Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536813034995/kp2461Isup3.cml
Synthesis of compound 1
2-Deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide (66.4 mg, 1.57 mmol) was added into a well-stirred mixture of 6-chloro-7-iodo-pyrrole[2,3-d]pyrimidine (400 mg, 1.43 mmol), potassium hydroxide (281.1 mg, 5.01 mmol) in anhydrous CH3CN (8 mL) at 273 K. The reaction mixture was allowed to warm to room temperature and kept for 16 h. After the solvent was removed in vacuo, the residue was purified by on silicagel to give I as a white solids.
Synthesis of compound 2
1(220.0 mg, 0.354 mmol) was suspended in 30 mL saturated methanolic ammonia and the solution was heated in a sealed bottle at 403 K for 12 h. The solution was evaporated in vacuo. The residue was purified by
on silica gel to afford 2 as a white solids. Crystals of the title compound (2) were obtained by slow evaporation of methanol.H atoms bond to N were located in a difference map and refined with distance of N—H = 0.86 Å or O—H = 0.82 Å and Uiso(H) = 1.2Ueq(N). other H atoms attached to C were fixed geometrically and treated as riding with C—H = 0.96 Å (methyl) or 0.93 Å (aromatic) and with Uiso(H) = 1.2Ueq(aromatic) or Uiso(H) = 1.5Ueq(methyl).
Fluorinated
containing fluorine atom(s) or fluorine containing groups in the sugar moiety or in the base moiety of greatly improve the bioactivity and stability of the corresponding compounds. The noteworthy of the fluorinated are FMAU, FIAC, FLT, gemcitabine (Etzold, et al., 1971; Watanabe, et al., 1979; Hertel, et al., 1988), which have high antiherpes and in some cases antitumour activities.In our study, we report a fluorinated nucleoside (Fig. 1). The three-dimensional structure and the packing of the title compound is shown Fig. 2 and hydrogen bonds geometry are summarized in Table 1. The orientation of the base relative to the sugar of purine χ (O1-C7-N4-C5),being in the title compound -anti, withχ= –129.0 (11)°. The phase angle of pseudorotation (P)is 67.6 (11)°, and the maximum amplitude of puckering (τm) is 39.5 (7)° (Saenger, 1983). The sugar ring adopts a D conformation (Evans & Boeyens, 1989), with an unsymmetrical twist O1-endo-C10-exo(oT4). The packing of the title compound is stabilized by hydrogen bonds, leading to a two-dimensional network (Fig. 3 and Table 1). The nucleobases are arranged head-to-head in a staircase-like fashion, in a pattern propagated by the a axis of the unit cell.
is defined by the torsion angleFor the biological activity of fluorinated
see: Etzold et al. (1971); Hertel et al. (1988); Watanabe et al. (1979). For puckering amplitudes, see: Saenger (1983). For sugar ring conformations, see: Evans & Boeyens (1989).Data collection: CrysAlis PRO (Agilent, 2013); cell
CrysAlis PRO (Agilent, 2013); data reduction: CrysAlis PRO (Agilent, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C11H12FIN4O3 | Z = 1 |
Mr = 394.15 | F(000) = 192 |
Triclinic, P1 | Dx = 1.986 Mg m−3 |
Hall symbol: P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.2602 (4) Å | Cell parameters from 1312 reflections |
b = 7.1570 (6) Å | θ = 2.9–28.5° |
c = 9.0126 (10) Å | µ = 2.46 mm−1 |
α = 84.533 (8)° | T = 293 K |
β = 83.400 (8)° | Block, colourless |
γ = 78.679 (7)° | 0.40 × 0.20 × 0.10 mm |
V = 329.57 (5) Å3 |
Agilent Xcalibur (Eos, Gemini) diffractometer | 1657 independent reflections |
Radiation source: Enhance (Mo) X-ray Source | 1657 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.012 |
ω scans | θmax = 25.0°, θmin = 2.9° |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2013) | h = −6→6 |
Tmin = 0.440, Tmax = 0.791 | k = −8→7 |
1874 measured reflections | l = −10→10 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.035 | w = 1/[σ2(Fo2) + (0.0711P)2 + 0.4273P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.101 | (Δ/σ)max < 0.001 |
S = 1.12 | Δρmax = 0.81 e Å−3 |
1657 reflections | Δρmin = −0.95 e Å−3 |
184 parameters | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
543 restraints | Extinction coefficient: 0.067 (7) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983) |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.02 (4) |
C11H12FIN4O3 | γ = 78.679 (7)° |
Mr = 394.15 | V = 329.57 (5) Å3 |
Triclinic, P1 | Z = 1 |
a = 5.2602 (4) Å | Mo Kα radiation |
b = 7.1570 (6) Å | µ = 2.46 mm−1 |
c = 9.0126 (10) Å | T = 293 K |
α = 84.533 (8)° | 0.40 × 0.20 × 0.10 mm |
β = 83.400 (8)° |
Agilent Xcalibur (Eos, Gemini) diffractometer | 1657 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2013) | 1657 reflections with I > 2σ(I) |
Tmin = 0.440, Tmax = 0.791 | Rint = 0.012 |
1874 measured reflections |
R[F2 > 2σ(F2)] = 0.035 | H-atom parameters constrained |
wR(F2) = 0.101 | Δρmax = 0.81 e Å−3 |
S = 1.12 | Δρmin = −0.95 e Å−3 |
1657 reflections | Absolute structure: Flack (1983) |
184 parameters | Absolute structure parameter: −0.02 (4) |
543 restraints |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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 | ||
I1 | 0.1930 | 0.6449 | 0.3463 | 0.0308 (2) | |
F1 | 0.429 (2) | 0.7543 (16) | 0.9462 (11) | 0.057 (3) | |
N1 | 0.461 (2) | 1.0608 (16) | 0.2063 (11) | 0.048 (2) | |
H1A | 0.4856 | 1.1477 | 0.1362 | 0.058* | |
H1B | 0.3686 | 0.9781 | 0.1935 | 0.058* | |
N2 | 0.711 (2) | 1.1864 (12) | 0.3508 (12) | 0.035 (2) | |
N3 | 0.8208 (15) | 1.0496 (10) | 0.5935 (8) | 0.0301 (14) | |
N4 | 0.667 (2) | 0.7549 (14) | 0.6696 (13) | 0.026 (2) | |
O1 | 0.936 (3) | 0.4908 (14) | 0.7689 (12) | 0.032 (2) | |
O2 | 0.8391 (16) | 0.4981 (11) | 1.1671 (8) | 0.0393 (16) | |
H2 | 0.9573 | 0.5579 | 1.1665 | 0.059* | |
O3 | 0.7857 (18) | 0.1388 (10) | 0.8929 (8) | 0.0499 (19) | |
H3 | 0.6824 | 0.2335 | 0.8651 | 0.075* | |
C1 | 0.430 (2) | 0.7432 (14) | 0.4790 (11) | 0.0288 (17) | |
C2 | 0.5445 (15) | 0.9116 (11) | 0.4542 (9) | 0.0231 (15) | |
C3 | 0.567 (2) | 1.0544 (15) | 0.3346 (11) | 0.0299 (19) | |
C4 | 0.820 (2) | 1.1806 (15) | 0.4769 (12) | 0.034 (2) | |
H4 | 0.9075 | 1.2797 | 0.4856 | 0.040* | |
C5 | 0.6830 (16) | 0.9159 (11) | 0.5735 (9) | 0.0239 (15) | |
C6 | 0.5113 (16) | 0.6501 (12) | 0.6100 (9) | 0.0266 (16) | |
H6 | 0.4693 | 0.5350 | 0.6525 | 0.032* | |
C7 | 0.8350 (17) | 0.6879 (12) | 0.7859 (9) | 0.0278 (16) | |
H7 | 0.9788 | 0.7584 | 0.7741 | 0.033* | |
C8 | 0.7021 (19) | 0.6988 (13) | 0.9462 (10) | 0.0327 (17) | |
H8 | 0.7699 | 0.7901 | 0.9980 | 0.039* | |
C9 | 0.774 (2) | 0.4980 (17) | 1.0223 (16) | 0.025 (2) | |
H9 | 0.6276 | 0.4317 | 1.0244 | 0.030* | |
C10 | 0.9965 (18) | 0.4065 (12) | 0.9139 (10) | 0.0289 (16) | |
H10 | 1.1607 | 0.4371 | 0.9366 | 0.035* | |
C11 | 1.022 (2) | 0.1922 (15) | 0.9151 (13) | 0.045 (2) | |
H11A | 1.1544 | 0.1445 | 0.8369 | 0.055* | |
H11B | 1.0774 | 0.1335 | 1.0104 | 0.055* |
U11 | U22 | U33 | U12 | U13 | U23 | |
I1 | 0.0289 (3) | 0.0375 (3) | 0.0286 (3) | −0.01214 (17) | −0.00417 (17) | −0.00181 (17) |
F1 | 0.056 (5) | 0.064 (6) | 0.032 (4) | 0.024 (4) | 0.007 (3) | 0.009 (4) |
N1 | 0.061 (6) | 0.051 (5) | 0.037 (5) | −0.022 (5) | −0.025 (5) | 0.025 (4) |
N2 | 0.044 (4) | 0.030 (5) | 0.031 (4) | −0.012 (5) | −0.008 (3) | 0.016 (4) |
N3 | 0.042 (3) | 0.027 (3) | 0.024 (3) | −0.014 (3) | −0.007 (3) | 0.004 (3) |
N4 | 0.038 (4) | 0.023 (4) | 0.017 (3) | −0.011 (3) | −0.006 (3) | 0.010 (3) |
O1 | 0.048 (4) | 0.023 (3) | 0.023 (4) | −0.006 (3) | 0.001 (3) | 0.006 (3) |
O2 | 0.057 (4) | 0.048 (4) | 0.021 (3) | −0.029 (3) | −0.017 (3) | 0.010 (3) |
O3 | 0.096 (6) | 0.031 (4) | 0.031 (4) | −0.030 (4) | −0.011 (4) | −0.002 (3) |
C1 | 0.030 (3) | 0.027 (4) | 0.029 (4) | −0.010 (3) | −0.004 (3) | 0.012 (3) |
C2 | 0.029 (3) | 0.022 (3) | 0.017 (3) | −0.008 (3) | −0.001 (3) | 0.010 (3) |
C3 | 0.035 (4) | 0.029 (4) | 0.024 (4) | −0.008 (3) | −0.005 (4) | 0.012 (3) |
C4 | 0.042 (5) | 0.031 (4) | 0.028 (4) | −0.011 (4) | −0.005 (4) | 0.011 (4) |
C5 | 0.033 (3) | 0.020 (3) | 0.018 (3) | −0.007 (3) | −0.003 (3) | 0.005 (3) |
C6 | 0.035 (3) | 0.027 (3) | 0.018 (3) | −0.012 (3) | −0.002 (3) | 0.007 (3) |
C7 | 0.040 (3) | 0.027 (3) | 0.019 (3) | −0.013 (3) | −0.008 (3) | 0.006 (3) |
C8 | 0.051 (4) | 0.028 (4) | 0.019 (3) | −0.009 (3) | −0.008 (3) | 0.006 (3) |
C9 | 0.038 (5) | 0.023 (4) | 0.020 (4) | −0.016 (4) | −0.017 (4) | 0.007 (3) |
C10 | 0.039 (4) | 0.026 (4) | 0.024 (4) | −0.009 (3) | −0.013 (3) | 0.005 (3) |
C11 | 0.062 (5) | 0.033 (4) | 0.037 (5) | −0.001 (4) | −0.014 (4) | 0.008 (4) |
I1—C1 | 2.080 (11) | O3—H3 | 0.8200 |
F1—C8 | 1.411 (16) | C1—C6 | 1.369 (13) |
N1—C3 | 1.332 (14) | C1—C2 | 1.438 (13) |
N1—H1A | 0.8600 | C2—C5 | 1.372 (12) |
N1—H1B | 0.8600 | C2—C3 | 1.424 (12) |
N2—C4 | 1.326 (16) | C4—H4 | 0.9300 |
N2—C3 | 1.350 (18) | C6—H6 | 0.9300 |
N3—C4 | 1.340 (12) | C7—C8 | 1.533 (12) |
N3—C5 | 1.345 (11) | C7—H7 | 0.9800 |
N4—C5 | 1.384 (12) | C8—C9 | 1.529 (14) |
N4—C6 | 1.393 (15) | C8—H8 | 0.9800 |
N4—C7 | 1.435 (14) | C9—C10 | 1.519 (17) |
O1—C7 | 1.423 (14) | C9—H9 | 0.9800 |
O1—C10 | 1.428 (13) | C10—C11 | 1.512 (13) |
O2—C9 | 1.387 (16) | C10—H10 | 0.9800 |
O2—H2 | 0.8200 | C11—H11A | 0.9700 |
O3—C11 | 1.408 (15) | C11—H11B | 0.9700 |
C3—N1—H1A | 120.0 | O1—C7—C8 | 105.9 (7) |
C3—N1—H1B | 120.0 | N4—C7—C8 | 115.4 (8) |
H1A—N1—H1B | 120.0 | O1—C7—H7 | 109.4 |
C4—N2—C3 | 119.3 (9) | N4—C7—H7 | 109.4 |
C4—N3—C5 | 111.9 (8) | C8—C7—H7 | 109.4 |
C5—N4—C6 | 107.7 (9) | F1—C8—C9 | 110.9 (9) |
C5—N4—C7 | 124.2 (10) | F1—C8—C7 | 111.0 (8) |
C6—N4—C7 | 126.3 (8) | C9—C8—C7 | 105.6 (8) |
C7—O1—C10 | 106.5 (9) | F1—C8—H8 | 109.8 |
C9—O2—H2 | 109.5 | C9—C8—H8 | 109.8 |
C11—O3—H3 | 109.5 | C7—C8—H8 | 109.8 |
C6—C1—C2 | 106.7 (9) | O2—C9—C10 | 114.3 (9) |
C6—C1—I1 | 124.3 (7) | O2—C9—C8 | 113.1 (10) |
C2—C1—I1 | 129.0 (6) | C10—C9—C8 | 101.9 (9) |
C5—C2—C3 | 116.5 (8) | O2—C9—H9 | 109.1 |
C5—C2—C1 | 107.4 (7) | C10—C9—H9 | 109.1 |
C3—C2—C1 | 135.8 (9) | C8—C9—H9 | 109.1 |
N1—C3—N2 | 118.4 (9) | O1—C10—C11 | 108.9 (8) |
N1—C3—C2 | 123.8 (10) | O1—C10—C9 | 105.4 (9) |
N2—C3—C2 | 117.7 (9) | C11—C10—C9 | 113.3 (9) |
N2—C4—N3 | 127.9 (10) | O1—C10—H10 | 109.7 |
N2—C4—H4 | 116.0 | C11—C10—H10 | 109.7 |
N3—C4—H4 | 116.0 | C9—C10—H10 | 109.7 |
N3—C5—C2 | 126.4 (7) | O3—C11—C10 | 112.3 (8) |
N3—C5—N4 | 124.6 (9) | O3—C11—H11A | 109.1 |
C2—C5—N4 | 108.9 (8) | C10—C11—H11A | 109.1 |
C1—C6—N4 | 109.2 (8) | O3—C11—H11B | 109.1 |
C1—C6—H6 | 125.4 | C10—C11—H11B | 109.1 |
N4—C6—H6 | 125.4 | H11A—C11—H11B | 107.9 |
O1—C7—N4 | 107.3 (9) |
D—H···A | D—H | H···A | D···A | D—H···A |
C8—H8···O3i | 0.98 | 2.60 | 3.247 (11) | 124 |
N1—H1A···O3ii | 0.86 | 2.55 | 3.189 (13) | 132 |
O2—H2···I1iii | 0.82 | 2.35 | 2.9933 | 136 |
Symmetry codes: (i) x, y+1, z; (ii) x, y+1, z−1; (iii) x+1, y, z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
C8—H8···O3i | 0.98 | 2.60 | 3.247 (11) | 123.9 |
N1—H1A···O3ii | 0.86 | 2.55 | 3.189 (13) | 132 |
O2—H2···I1iii | 0.82 | 2.35 | 2.9933 | 136 |
Symmetry codes: (i) x, y+1, z; (ii) x, y+1, z−1; (iii) x+1, y, z+1. |
Acknowledgements
This work was supported by National Natural Science Foundation (NSFC, Nos. 20962009, 21062006) and the Science Fund of the Education Office of Jiangxi (GJJ12583).
References
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Fluorinated nucleosides, containing fluorine atom(s) or fluorine containing groups in the sugar moiety or in the base moiety of nucleosides, greatly improve the bioactivity and stability of the corresponding compounds. The noteworthy of the fluorinated nucleosides are FMAU, FIAC, FLT, gemcitabine (Etzold, et al., 1971; Watanabe, et al., 1979; Hertel, et al., 1988), which have high antiherpes and in some cases antitumour activities.
In our study, we report a fluorinated nucleoside (Fig. 1). The three-dimensional structure and the packing of the title compound is shown Fig. 2 and hydrogen bonds geometry are summarized in Table 1. The orientation of the base relative to the sugar of purine nucleosides is defined by the torsion angle χ (O1-C7-N4-C5),being in the title compound -anti, withχ= –129.0 (11)°. The phase angle of pseudorotation (P)is 67.6 (11)°, and the maximum amplitude of puckering (τm) is 39.5 (7)° (Saenger, 1983). The sugar ring adopts a D conformation (Evans & Boeyens, 1989), with an unsymmetrical twist O1-endo-C10-exo(oT4). The packing of the title compound is stabilized by hydrogen bonds, leading to a two-dimensional network (Fig. 3 and Table 1). The nucleobases are arranged head-to-head in a staircase-like fashion, in a pattern propagated by the a axis of the unit cell.