[(2R,3S,5R)-3-Acet­oxy-5-(5-formyl-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-1-yl)-2,3,4,5-tetra­hydro­furan-2-yl]methyl acetate

Xue-Fei Jia; Nan Liu; Liang-Liang Fang; Xin-Ying Zhang

doi:10.1107/S1600536811041304

. 2011 Oct 12;67(Pt 11):o2951–o2952. doi: 10.1107/S1600536811041304

[(2R,3S,5R)-3-Acetoxy-5-(5-formyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-2,3,4,5-tetrahydrofuran-2-yl]methyl acetate

Xue-Fei Jia ^a, Nan Liu ^a, Liang-Liang Fang ^a, Xin-Ying Zhang ^a,^*

PMCID: PMC3247360 PMID: 22219978

Abstract

In the two independent but very similar molecules (A and B) of the title compound, C₁₄H₁₆N₂O₈, both six-membered pyrimidine rings are nearly planar [maximum deviations = 0.010 (3) Å in A and 0.028 (3) Å in B]. The five-membered furanose ring in molecule A adopts an envelope conformation, while the same ring in molecule B has a twisted conformation. In the crystal, the A molecules are linked via a pair of intermolecular N—H⋯O hydrogen bonds, forming dimers. Each A molecule is further linked to a B molecule via a second N—H⋯O hydrogen bond. There are also a number of C—H⋯·O interactions present, leading to the formation of a three-dimensional network.

Related literature

For the bioactivity of 5-substituted pyrimidine nucleosides, see: De Clercq (2005 ▶); Agrofoglio et al. (2003 ▶); Lee et al. (2009 ▶). For the use of the title compound as a synthon for the preparation of a variety of nucleoside derivatives, see: Fan et al. (2006a ▶,b ▶, 2010 ▶, 2011 ▶); Zhang et al. (2009 ▶). For related structures of uridines, see: Luo et al. (2007 ▶); Low & Wilson (1984 ▶).

Experimental

Crystal data

C₂₈H₃₂N₄O₁₆
M _r = 680.58
Orthorhombic,
a = 15.5268 (18) Å
b = 29.977 (4) Å
c = 6.6207 (8) Å
V = 3081.6 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 296 K
0.24 × 0.18 × 0.09 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2007 ▶) T _min = 0.971, T _max = 0.989
23677 measured reflections
5719 independent reflections
3519 reflections with I > 2σ(I)
R _int = 0.060

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.110
S = 1.01
5719 reflections
437 parameters
H-atom parameters constrained
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.17 e Å⁻³
Absolute structure: Flack (1983 ▶), 2320 Friedel pairs
Flack parameter: −0.6 (12)

Data collection: SMART (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; 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/S1600536811041304/su2320sup1.cif

e-67-o2951-sup1.cif^{(29.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811041304/su2320Isup2.hkl

e-67-o2951-Isup2.hkl^{(280KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811041304/su2320Isup3.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
N2—H2⋯O6ⁱ	0.86	1.96	2.817 (3)	172
N4—H4A⋯O5	0.86	2.08	2.935 (4)	173
C3—H3⋯O13	0.98	2.57	3.489 (4)	156
C13—H13⋯O2	0.93	2.54	3.402 (4)	155
C16—H16A⋯O7ⁱⁱ	0.97	2.41	3.312 (4)	155
C18—H18⋯O10ⁱⁱⁱ	0.98	2.46	3.257 (4)	138
C21—H21A⋯O4^iv	0.96	2.51	3.441 (5)	162

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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 20972042) and the Natural Science Foundation of Department of Education of Henan Province (No. 2009 A150017).

supplementary crystallographic information

Comment

Many pyrimidine nucleosides with modification on the 5-position of the pyrimidine ring have drawn much attention due to their interesting pharmacological properties, such as antitumor, antiviral, and antimicrobial activities (De Clercq et al., 2005; Agrofoglio et al., 2003, Lee et al., 2009). The title compound has been used as a powerful synthon for the preparation of a variety of nucleoside derivatives due to the rich and extensive chemistry of the aldehyde carbonyl (Fan et al., 2006a, 2006b, 2010, 2011; Zhang et al., 2009). However, its crystal structure has not been reported as yet.

The absolute structure of the title compound is known because the synthetic procedure does not affect stereogenic atoms of the starting compound. In the two independent (A & B) but very similar molecules of the title compound (Fig. 1) all the bond lengths and bond angles are within normal ranges. In molecule A the O1—C4 bond is a little longer than bond O1—C1, as is bond O16-C15 compared to bond O16-C18 in molecule B. This is similar to the situation in 2'-deoxy-3',5'-di-O-acetyluridine (Luo et al., 2007), but different to that in 2,3,5-triacetyluridine (Low & Wilson, 1984).

The pyrimidine rings in both molecules are planar [maximum deviations being 0.010 (3) Å in A and 0.028 (3) Å in B]. The atoms connected directly with the pyrimidine ring and the atoms in the aldehyde carbonyl group in the 5-position of the pyrimidine ring are coplanar with the pyrimidine ring, which means there is an exstensive conjugated system in each molecule. The five-membered furanose ring in molecule A adopts an envelope conformation with atom C2 at the flap, while in molecule B the five-membered ring is twisted on bond C15-C16.

In the crystal, two A molecules form a pseudosymmetric dimer connected via N—H···O hydrogen bonds, involving the N atom of the pyrimidine base and the adjacent carbonyl O atom of the pyrimidine base. Each A molecule is further connected to a B molecule via an N—H···O hydrogen bond involving the N atom of the pyrimidine base and carbonyl O atom of the acetoxy groups in the 3'-position of the furanose ring (see Table 1 and Fig. 2 for details). There are also a number of C-H···O interactions present leading to the formation of a three-dimensional network (Table 1).

Experimental

The title compound was synthesized following the previously reported procedure (Fan, et al., 2006b). Single crystals, suitable for X-ray diffraction analysis, were obtained by slow evaporation of the solvents from a dichloromethane-petroleum ether (1:1 v/v) solution of the title compound.