(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo­[2,3-d]pyrimidin-7-yl)-5-methyl­tetra­hydro­furan-3,4-diol

Ulrich Flörke; Birte Drewes

doi:10.1107/S1600536813027931

. 2013 Oct 16;69(Pt 11):o1646–o1647. doi: 10.1107/S1600536813027931

(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-methyltetrahydrofuran-3,4-diol

Ulrich Flörke ^a,^*, Birte Drewes ^b

PMCID: PMC3884313 PMID: 24454089

Abstract

The molecular structure of the title compound, C₁₁H₁₃IN₄O₃, shows a ribofuranosyl–pyrrolo O—C—N—C torsion angle of 59.1 (3)°, with the central C—N bond length being 1.446 (3) Å. The C—I bond length is 2.072 (2) Å. The amino group is coplanar with the attached aromatic ring [C—N—C—N torsion angle = −178.8 (2)°] and forms an intramolecular N—H⋯I hydrogen bond. In the crystal, O—H⋯N and N—H⋯O hydrogen bonds link the molecules into puckered layers parallel to (001). These layers are bound to each other by secondary I⋯O interactions [3.2250 (17) Å], forming a three-dimensional framework.

Related literature

For background to the use of marine natural products as therapeutic agents, see: Kazlauskas et al. (1983 ▶); Mitchell et al. (1996 ▶); Wiesner et al. (1999 ▶); Ugarkar et al. (2000 ▶); Song et al. (2011 ▶). For the structures of related compounds, see: Seela et al. (1996 ▶, 1999 ▶, 2008 ▶). graphic file with name e-69-o1646-scheme1.jpg

Experimental

Crystal data

C₁₁H₁₃IN₄O₃
M _r = 376.15
Orthorhombic,
a = 4.9164 (2) Å
b = 14.6490 (5) Å
c = 18.0130 (6) Å
V = 1297.30 (8) Å³
Z = 4
Mo Kα radiation
μ = 2.48 mm⁻¹
T = 130 K
0.49 × 0.08 × 0.08 mm

Data collection

Bruker SMART APEX diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ▶) T _min = 0.376, T _max = 0.826
12307 measured reflections
3103 independent reflections
3056 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.020
wR(F ²) = 0.051
S = 1.06
3103 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 1.05 e Å⁻³
Δρ_min = −0.30 e Å⁻³
Absolute structure: Flack (1983 ▶), 1274 Friedel pairs
Absolute structure parameter: −0.015 (17)

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2002 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and local programs.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813027931/kq2009sup1.cif

e-69-o1646-sup1.cif^{(24.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813027931/kq2009Isup2.hkl

e-69-o1646-Isup2.hkl^{(152.3KB, hkl)}

Click here for additional data file.^{(5.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813027931/kq2009Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N2ⁱ	0.84	1.94	2.759 (3)	165
O3—H3⋯N1ⁱⁱ	0.84	2.16	2.907 (3)	149
N4—H4A⋯O2ⁱⁱⁱ	0.88	2.07	2.915 (3)	160
N4—H4B⋯I1	0.88	2.92	3.636 (2)	139

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

supplementary crystallographic information

1. Comment

Marine natural products provide a rich source of chemical diversity that can be used to develop new, potentially useful therapeutic agents. Nucleosides from marine organisms show great potential as lead compounds in medicinal chemistry research. 5'-Deoxy-5-iodotubercidin (5'd-5IT, 4-amino-5-iodo-7-(5-deoxy-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine) was isolated from the marine red alga Hypnea vanlendiae (Kazlauskas et al., 1983) and from the marine ascidian Didemnum voeltzkowi (Mitchell et al., 1996). In vitro, all 5'-deoxytubercidin marine nucleosides show strong inhibitory activity for human adenosine kinase with 5'd-5IT being the most potent one. Therapeutic success of adenosine kinase inhibitors as active agents in animal models is documented for epilepsy and pain and as antiseizure agents (Wiesner et al., 1999; Ugarkar et al., 2000). The molecular structure is related to the derivatives studied previously (Seela et al., 1996, 1999, 2008) and shows no unexpected geometric parameters.

2. Experimental

The title compound was synthesized according to a known procedure (Song et al., 2011). Recrystallization from ethanol-water (1:1) yielded crystals suitable for X-ray analysis. Spectroscopic analysis: ¹H NMR (250 MHz, DMSO-d6, δ): 1.29 (d, J = 6.16 Hz, 3H, CHCH₃), 3.87–3.95 [m, 2H, H-3', H-4'], 4.41 (m, 1H, H-2'), 5.11 (s, 1H, 3'-OH), 5.33 (s, 1H, 2'-OH), 6.02 (d, J = 5.28 Hz, 1H, H-1'), 6.69 (s, 2H, 4-NH₂), 7.63 (s, 1H, H-6), 8.14 (s, 1H, H-2); ¹³C NMR (250 MHz, DMSO-d6, δ): 19.6 (CH₃, C-5'), 52.8 (C—I, C-5), 73.8 (CH, C-2'), 75.0 (CH, C-3'), 79.8 (CH, C-4'), 87.4 (CH, C-1'), 103.6 (C═C, C-4a), 127.4 (CH, C-6), 150.8 (C═C, C-7a), 152.5 (CH, C-2), 157.6 (C—NH₂, C-4).