(2R,3S,4R,5R)-5-(4-Amino-5-iodo-7H-pyrrolo­[2,3-d]pyrimidin-7-yl)-4-fluoro-2-(hy­droxy­meth­yl)tetra­hydro­furan-3-ol

Wei Li; Ruchun Yang; Qiang Xiao

doi:10.1107/S1600536813034995

. 2014 Jan 8;70(Pt 2):o120. doi: 10.1107/S1600536813034995

(2R,3S,4R,5R)-5-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol

Wei Li ^a, Ruchun Yang ^a,^*, Qiang Xiao ^a

PMCID: PMC3998288 PMID: 24764849

Abstract

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.

Related literature

For the biological activity of fluorinated nucleosides, 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 ▶). graphic file with name e-70-0o120-scheme1.jpg

Experimental

Crystal data

C₁₁H₁₂FIN₄O₃
M _r = 394.15
Triclinic,
a = 5.2602 (4) Å
b = 7.1570 (6) Å
c = 9.0126 (10) Å
α = 84.533 (8)°
β = 83.400 (8)°
γ = 78.679 (7)°
V = 329.57 (5) Å³
Z = 1
Mo Kα radiation
μ = 2.46 mm⁻¹
T = 293 K
0.40 × 0.20 × 0.10 mm

Data collection

Agilent Xcalibur (Eos, Gemini) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2013 ▶) T _min = 0.440, T _max = 0.791
1874 measured reflections
1657 independent reflections
1657 reflections with I > 2σ(I)
R _int = 0.012

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.101
S = 1.12
1657 reflections
184 parameters
543 restraints
H-atom parameters constrained
Δρ_max = 0.81 e Å⁻³
Δρ_min = −0.95 e Å⁻³
Absolute structure: Flack (1983 ▶)
Absolute structure parameter: −0.02 (4)

Data collection: CrysAlis PRO (Agilent, 2013 ▶); cell refinement: 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.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813034995/kp2461sup1.cif

e-70-0o120-sup1.cif^{(16.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813034995/kp2461Isup2.hkl

e-70-0o120-Isup2.hkl^{(81.6KB, hkl)}

Click here for additional data file.^{(5.6KB, cml)}

Supporting information file. DOI: 10.1107/S1600536813034995/kp2461Isup3.cml

CCDC reference: http://scripts.iucr.org/cgi-bin/cr.cgi?rm=csd&csdid=979239

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

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

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported by National Natural Science Foundation (NSFC, Nos. 20962009, 21062006) and the Science Fund of the Education Office of Jiangxi (GJJ12583).

supplementary crystallographic information

1. Comment

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 (τ_m) 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.

2. Experimental

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 column chromatography 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 column chromatography on silica gel to afford 2 as a white solids. Crystals of the title compound (2) were obtained by slow evaporation of methanol.