3′-O-Acetyl-2′-de­oxy­uridine

Bogdan Doboszewski; Alexander Y Nazarenko; Victor N Nemykin

doi:10.1107/S160053681004938X

. 2010 Dec 4;67(Pt 1):o3–o4. doi: 10.1107/S160053681004938X

3′-O-Acetyl-2′-deoxyuridine

Bogdan Doboszewski ^a, Alexander Y Nazarenko ^b,^*, Victor N Nemykin ^c

PMCID: PMC3050423 PMID: 21522742

Abstract

In the two independent but very similar molecules of the title compound, C₁₁H₁₄N₂O₆, both nucleobase fragments are nearly planar (both within 0.01 Å) while the furanose rings exhibit ² E-endo envelope conformations. In the crystal, the two 3′-O-acetyl-2′-deoxyuridine molecules form a pseudosymmetric dimer of two bases connected via two nearly identical resonance-assisted N—H⋯O hydrogen bonds. The resulting pair is further connected with neighboring pairs via two similar O—H⋯O bonds involving the only hydroxyl group of the 2′-deoxyfuranose fragment and the remaining carbonyl oxygen of the nucleobase. These interactions result in the formation of an infinite ‘double band’ along the b axis that can be considered as a self-assembled analogue of a polynucleotide molecule with non-canonical Watson–Crick base pairs. The infinite chains of 3′-O-acetyl-2′-deoxyuridine pairs are additionally held together by C—H⋯O interactions involving C atoms of the uracyl base and O atoms of carbonyl groups. Only weak C—H⋯O contacts exist between neighboring chains.

Related literature

For syntheses of this and similar compounds, see: Smrt & Sorm (1960 ▶); Cabral et al. (2008 ▶). For related structures of uridines, see: de Graaff et al. (1977 ▶); Green et al. (1975 ▶); Low & Wilson (1984 ▶); Luo et al. (2007 ▶); Marck et al. (1982 ▶); Rahman & Wilson (1972 ▶); Suck et al. (1972 ▶). For conformations of five-membered rings, see: Schwarz (1973 ▶); Cremer & Pople (1975 ▶); Boeyens & Dobson (1987 ▶). For analysis of absolute structure, see: Flack (1983 ▶), Hooft et al. (2008 ▶). For hydrogen bonding in nucleotide chemistry, see: Gilli & Gilli (2009 ▶); Desiraju & Steiner (1999 ▶); Jeffrey (1997 ▶); Nagaswamy et al.(2000 ▶) and references therein. For similar UU-4-carbonyl–imino pairs in RNA structures, see: Ban et al. (2000 ▶); Jiang & Patel (1998 ▶).

Experimental

Crystal data

C₁₁H₁₄N₂O₆
M _r = 270.24
Monoclinic,
a = 22.8919 (4) Å
b = 6.8676 (1) Å
c = 17.2789 (12) Å
β = 111.307 (8)°
V = 2530.8 (2) Å³
Z = 8
Cu Kα radiation
μ = 1.00 mm⁻¹
T = 291 K
0.2 × 0.15 × 0.1 mm

Data collection

Rigaku R-AXIS RAPID II imaging plate diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.84, T _max = 0.88
11957 measured reflections
4372 independent reflections
2609 reflections with I > 2σ(I)
R _int = 0.069

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.149
S = 1.10
4372 reflections
346 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.24 e Å⁻³
Absolute structure: Flack (1983 ▶), 1927 Friedel pairs
Flack parameter: 0.0 (2)

Data collection: CrystalClear-SM Expert (Rigaku, 2009 ▶); cell refinement: CrystalClear-SM Expert; data reduction: CrystalClear-SM Expert; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681004938X/zl2331sup1.cif

e-67-000o3-sup1.cif^{(25.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681004938X/zl2331Isup2.hkl

e-67-000o3-Isup2.hkl^{(214.3KB, hkl)}

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

Enhanced figure: interactive version of Fig. 7

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H1⋯O1ⁱ	0.82	1.98	2.798 (5)	173
N2—H2⋯O22ⁱⁱ	0.86	1.98	2.803 (5)	161
N22—H22⋯O2ⁱⁱ	0.86	1.99	2.817 (5)	160
O24—H24⋯O21ⁱⁱⁱ	0.82	2.02	2.828 (5)	170
C3—H3A⋯O22^iv	0.93	2.24	3.117 (6)	157
C23—H23A⋯O2^v	0.93	2.39	3.254 (5)	154
C24—H24A⋯O21ⁱⁱⁱ	0.93	2.59	3.381 (5)	143
C31—H31B⋯O26^vi	0.96	2.56	3.428 (8)	150

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

Acknowledgments

This study was supported by the NSF (grant CHE-0922366 for X-ray diffractometer) and by SUNY (grant No 1073053).

supplementary crystallographic information

Comment

Modified nucleosides have received much attention as potential chemotherapeutic agents due to their ability to interfere with the polymerases engaged in replication processes in metastatic or virus invaded cells. In fact, most of the antiviral compounds approved for commercialization are nucleoside analogs which were obtained by modifications of the ribonucleosides or deoxyribonucleosides at a nucleobase moiety, at a carbohydrate moiety or at both of them. The title compound has attracted our attention as a possible intermediate in a synthesis of such agents.

The absolute structure of the title compound is known from the synthetic route which does not affect stereogenic atoms of the starting compound. Nevertheless, we preferred to obtain a direct experimental confirmation using X-ray diffractometry data. Because there are no heavy atoms in a chiral molecule of title compound, Cu Kα radiation was necessary for determination of the absolute structure.

In the crystal structure of title compound (Fig.1), all bond lengths and bond angles have standard dimensions.

The six-membered rings in both crystallographically independent molecules are flat within 0.01 Å. Figure 2 shows that the furanose ring in the first molecule adopts an envelope conformation with atoms O3, C7, C8, and C5 being within 0.02 Å from their mean plane, and atom C6 at a distance of 0.48 Å. A quantitative analysis of the ring conformations was performed using the method of Cremer and Pople (Cremer & Pople, 1975; Boeyens & Dobson, 1987) for the calculation of parameters of puckering. The polar parameters for the furanose ring are Q = 0.301 (4) and 0.320 (4) Å, Φ = 67.1 (8)° and 66.6 (7) ° for both independent molecules. These suggest the envelope conformation ²E (ideal Φ = 72°), slightly distorted towards twist ²T₁ (Φ= 54°), with atoms C(6) and C(26) in corners of the respective envelopes. The conformation of the 3'-substituted 2'-deoxydeoxyuridine reported here is different from the conformation of the unsubstituted 2'-deoxyuridine molecule: in this case Φ = 83 and Φ = 89 ° for two independent molecules which is close to a twisted ²T₃ conformation (Φ=90°) of the furanose ring (CSD code DOURID, Rahman & Wilson, 1972). An ²E conformation was observed in several other molecules of the uridine family (see, for example 2'-deoxy-3',5'-diacetyldeoxyuridine (WEVJOX, Luo et al., 2007) Φ = 67 °; 3,5-diacetyluridine (DAURID, de Graaff et al., 1977) Φ =76 °; and 2'-chloro-2'-deoxyuridine (CDURID, Suck et al., 1972) Φ =69 °). ³E and ³T₂ conformations exist in uridine (BEURID10, Green et al., 1975) with Φ =282 ° and 273 °. Twisted conformations ^OT₅and ³T₄ are observed in 2'deoxy-2'-fluorodeoxyuridine (BOFWIC, Marck et al., 1982) Φ =339 ° and 2,3,5-triacetyluridine (CIHNIK, Low & Wilson, 1984) Φ =313 °. Therefore, no direct correlation between the substituents, their properties, and the furanose ring conformation is obvious.

In the crystal of the title compound, the two independent acetyldeoxyuridine molecules form a pseudosymmetric dimer of two bases connected via two nearly identical N—H···O hydrogen bonds (Table 1, Figure 3). Such pseudosymmetric arrangment corresponds to a UU4² mode of base pairing (Jeffrey, 1997). Relatively short N···O separations (Table 1) demonstrate strong resonance-assisted hydrogen bonds. All eight cycle-forming atoms are located close to the mean plane (Figure 3), making possible π-delocalization of the resonance fragment. This observation is also supported by longer C=O bond lengths in the participating carbonyl groups (1.236 (5) and 1.230 (5) Å) when compared to the other carbonyl groups of the same nucleobase (1.223 (5) and 1.212 (5) Å).

The resulting dimer is further connected with neighboring dimers via two similar O—H···O bonds involving the only hydroxy group of deoxyfuranose fragment and the remaining carbonyl oxygen of the base. These interactions result in the formation of infinitive "double bands" along the b axis of the crystal cell (Figure 4). Such a structure can be considered as a primitive self-assembled analogue of an RNA polymer molecule with non-canonical Watson-Crick base pairs. Two examples of similar UU-4-carbonyl-immino pairs in RNA structures can be found in an NMR structure (Jiang & Patel, 1998) and in a low resolution solid state structure (Ban et al., 2000). More information about flipped pyrimidine-pyrimidine mismatches can be found in (Nagaswamy et al., 2000).

The infinitive chains of acetyldeoxyuridine pairs in the title compound are additionally kept together by CH···O interactions involving carbon atoms of the uracyl base and oxygen atoms of carbonyl groups (Table 1, Figure 4 and 5). Similar bonds were observed in various uracyl-containg structures (Desiraju & Steiner, 1999). A short intramolecular contact between carbonyl oxygen O1 and hydrogen atom H5A may additionaly stabilize the conformation of the molecule.

Only weak C—H···O contacts exist between neighboring chains.

Experimental

The synthesis of the title compound was accomplished via a transetherification procedure dubbed "protecting group transfer" (Cabral et al., 2008). 3'-Acetyl-2'-deoxyuridine obtained in this way showed the same properties as the one obtained before by an independent procedure (Smrt & Sorm, 1960). Crystallization from a hexane-acetone system yielded colourless crystals suitable for single-crystal diffractometry (m.p. 460–461 K).