7-Cyclo­propyl-2′-de­oxy­tubercidin: a carbocyclic side-chain derivative of 7-de­aza-2′-de­oxy­adenosine

The title compound {systematic name: 4-amino-5-cyclo­propyl-7-(2-de­oxy-β-D-erythro-pento­furan­osyl)-7H-pyrrolo­[2,3-d]pyrimidine}, C₁₄H₁₈N₄O₃, exhibits an anti glycosylic bond conformation, with the torsion angle χ = −108.7 (2)°. The furan­ose group shows a twisted C1′-exo sugar pucker (S-type), with P = 120.0 (2)° and τ_m = 40.4 (1)°. The orientation of the exocyclic C4′—C5′ bond is -ap (trans), with the torsion angle γ = −167.1 (2)°. The cyclo­propyl substituent points away from the nucleobase (anti orientation). Within the three-dimensional extended crystal structure, the individual mol­ecules are stacked and arranged into layers, which are highly ordered and stabilized by hydrogen bonding. The O atom of the exocyclic 5′-hy­droxy group of the sugar residue acts as an acceptor, forming a bifurcated hydrogen bond to the amino groups of two different neighbouring mol­ecules. By this means, four neighbouring mol­ecules form a rhomboidal arrangement of two bifurcated hydrogen bonds involving two amino groups and two O5′ atoms of the sugar residues.

S1. Introduction

The ribonucleoside tubercidin [7-de­aza­adenosine, (IIa); purine numbering is used throughout this discussion] is a close structural analogue of adenosine and shows significant biological activities (Suhadolnik, 1970). The anti­biotic was isolated from Streptomyces tubercidicus (Anzai et al., 1957), and its crystal structure was reported by Stroud (1973) and by Abola & Sundaralingam (1973). The single-crystal X-ray structure of the related DNA analogue 2'-de­oxy­tubercidin, (IIb), was reported by Zabel et al. (1987).

A series of 7-substituted tubercidin derivatives show anti­viral activity against RNA and DNA viruses, including herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) (Bergstrom et al., 1984; De Clercq et al., 1986). Furthermore, both 2'-C-methyl­tubercidin and its 7-fluoro derivative are potent and selective inhibitors of hepatitis C virus (HCV) RNA replication (Olsen et al., 2004; Eldrup et al., 2004).

The cyclo­propyl group – the 7-substituent of the title compound, (I) – is a constituent of many naturally occurring terpenes (Franck-Neumann et al., 1985), amino acids (Brackmann & de Meijere, 2007) and even nucleosides isolated from the fermentation broth of various bacteria (Barrett & Kasdorf, 1996; Charette & Lebel, 1996). It is also part of the anti­virally active drug abacavir (systematic name: {4-[2-amino-6-(cyclo­propyl­amino)-9H-purin-9-yl]cyclo­pent-2-enyl}methanol) (Vince & Hua, 2006), which is the prodrug of carbovir (Vince & Hua, 1990). Other pharmacologically active nucleosides, such as 5-cyclo­propyl-2'-de­oxy­uridine, 5-cyclo­propyl-2'-de­oxy­cytidine and 9-{[cis-1',2'-bis­(hy­droxy­methyl)­cyclo­prop-1'-yl]methyl}­guanine (Peters et al., 1992; Sekiyama et al., 1998) contain this carbocycle as well. Purine nucleosides with a cyclo­propyl group linked to the pyrimidine group were reported by Hocek and co-workers (Kuchař et al., 2008).

The steric demand of a cyclo­propyl group lies between an ethyl and an iso­propyl group. The angle strain of its ring system also holds greater potential energy than its corresponding alkanyl group and is similar to an olefinic double bond. There are two equivalent descriptions of the cyclo­propyl system, one by the MO model by Walsh and the other by the VB model by Förster refined by Coulson (de Meijere et al., 1979). Usually, functional groups introduced at the 7-position of 2'-de­oxy­tubercidin are well accommodated in the DNA helix structure when these compounds are incorporated in DNA.

In the me­antime, single-crystal X-ray studies of several 7-substituted tubercidin derivatives have been reported (Seela et al., 2005, 2006, 2008). For that reason, we became inter­ested in the X-ray single-crystal structure of the title 2'-de­oxy­tubercidin derivative, (I), bearing a cyclo­propyl group in the 7-position and we wished to compare its solid-state structure with those of the closely related nucleosides tubercidin, (IIa) (Stroud, 1973; Abola & Sundaralingam, 1973), 2'-de­oxy­tubercidin, (IIb) (Zabel et al., 1987), and 2'-de­oxy-7-propynyltubercidin, (III) (Seela et al., 2006).

To the best of our knowledge, (I) is the first 7-de­aza­purine 2'-de­oxy­ribonucleoside in which the pyrrolo group is functionalized by a cyclo­propyl group. Related sugar-modified ribonucleoside derivatives bearing various functional groups at the 2'-position of the sugar residue have already been reported (Chen et al., 2010).

S2. Experimental

S2.1. Synthesis and crystallization

Compound (I) was synthesized by nucleobase anion glycosyl­ation of 4-chloro-5-cyclo­propyl-pyrrolo­[2,3-d]pyrimidine (Seela et al., 2007) with 2-de­oxy-3,5-di-O-p-toluoyl-D-erythro-pentosyl chloride in aceto­nitrile. Details of the synthesis will be described elsewhere. Nucleoside (I) crystallizes from ethyl acetate as colourless needles (m.p. 466 K). For the diffraction experiment, a single crystal was mounted on a MiTeGen Micro-Mounts fibre in a thin smear of oil.

S2.2. Refinement

The known configuration of the parent molecule was used to define the enanti­omer employed in the refined model. In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absolute structure. Refinement of the Flack (1983) parameter led to an inconclusive value for this parameter [0.0 (6)]. All H atoms were found in a difference Fourier synthesis. In order to maximize the data:parameter ratio, the H atoms were placed in geometrically idealized positions, with C—H = 0.95–1.00 Å, and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C) = U_eq(N). The hy­droxy functions were refined as groups allowed to rotate but not tip (AFIX 147 command in SHELXTL; Sheldrick, 2008), with O—H = 0.84 Å and U_iso(H) = 1.5U_eq(O).

S3. Results and discussion

The three-dimensional structure of (I) is shown in Fig. 1 and selected geometric parameters are summarized in Table 2. The three 2'-de­oxy­ribonucleosides, (I), (IIb) and (III), crystallize in the same space group, i.e. orthorhombic P2₁2₁2₁ (Zabel et al., 1987; Seela et al., 2006), while it is monoclinic P2₁ for the parent ribonucleoside tubercidin, (IIa) (Stroud, 1973).

The orientation of the nucleobase relative to the sugar residue (syn/anti) is defined by the torsion angle χ (O4'—C1'—N9—C4) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). For natural purine 2'-de­oxy­ribonucleosides, the preferred conformation around the N-glycosylic bond is anti (Saenger, 1984). Accordingly, (I) shows an anti conformation, with the torsion angle χ = -108.7 (2)°. The related nucleosides (IIa) and (IIb), as well as (III), also adopt χ values corresponding to the anti conformation [χ = -112.8 (4)° for (IIa) (Abola & Sundaralingam, 1973); χ = -104.4 (2)° for (IIb) (Zabel et al., 1987); χ = -130.7 (2)° for (III) (Seela et al., 2006)].

The length of the glycosylic bond N9—C1' of (I) is 1.446 (2) Å, which is within the same range as those observed for (IIa) [1.438 (4) Å; Abola & Sundaralingam, 1973], (IIb) [1.449 (2) Å; Zabel et al., 1987] and (III) [1.457 (3) Å; Seela et al., 2006].

The most frequently observed sugar-ring conformations of nucleosides are C2'-endo (`south') and C3'-endo (`north') (Arnott & Hukins, 1972). The 2'-de­oxy­ribose ring of (I) shows an S-type conformation, with the pseudorotation phase angle P = 120.0 (2)° and a maximum puckering amplitude τ_m = 40.4 (1)° (Altona & Sundaralingam, 1972), referring to a major C1'-exo conformation (C1'-exo-O4'-endo, ₁T^O). In contrast, in the case of the closely related 2'-de­oxy­ribonucleosides (IIb) and (III), the sugar-ring conformations are C3'-exo-C2'-endo (₃T²; S-type), with P = 186.6 (2)° for (IIb) (Zabel et al., 1987) and P = 185.9 (2)° for (III) (Seela et al., 2006), while (IIa) adopts an S-type sugar conformation with P = 149.3° (C2'-endo-C1'-exo, ²T₁) (Abola & Sundaralingam, 1973).

The sugar conformation of nucleoside (I) was also determined in solution and compared with the conformation of the parent 2'-de­oxy­tubercidin (IIb). In solution, both compounds show a predominantly S conformation [74% S for (I) and 76% S for (IIb); Rosemeyer et al., 1997], which is consistent with their sugar conformation in the solid state. The conformation analysis was performed on the basis of the vicinal ³J(H,H) coupling constants of ¹H NMR spectra measured in a D₂O/di­methyl sulfoxide mixture, applying the program PSEUROT 6.3 (Van Wijk et al., 1999).

The γ torsion angle (O5'—C5'—C4'—C3') characterizes the orientation of the exocyclic 5'-hy­droxy group relative to the sugar ring (Saenger, 1984). The C4'—C5' bond conformation of (I) is anti­periplanar (-ap; trans), with the torsion angle γ = -167.1 (2)°. The related crystal structures of nucleosides (IIa), (IIb) and (III) also display anti­periplanar conformations around the C4'—C5' bond [(IIa): γ = -178.3 (4)° (-ap) (Abola & Sundaralingam, 1973); (IIb): γ = 179.6 (2)° (ap) (Zabel et al., 1987); (III): γ = -172.7 (3)° (-ap) (Seela et al., 2006)].

The 7-de­aza­purine ring system of (I) is almost planar. The deviations of the ring atoms (N1/C2/N3/C4–C8/N9) from the least-squares plane range from -0.009 (2) Å for atom C7 to 0.011 (2) Å for atom C6, with an r.m.s. deviation of 0.0055 Å. Atom C18 of the cyclo­propyl substituent and atom C1' of the sugar residue lie on the same side of the plane of the heterocycle [at 0.029 (3) and 0.132 (3) Å, respectively].

According to the definition of the orientation of the nucleobase relative to the sugar residue (syn/anti) as described above, the relative positioning of the cyclo­propyl group towards the nucleobase can also be described using the terms syn/anti. In anti, the cyclo­propyl group points away from the nucleobase, while in syn it is positioned over or towards the nucleobase. To this end, we arbitrarily define the torsion angle C19—C18—C7—C5 to be syn when the torsion angle C19—C18—C7—C5 is between -90 and 90°, and it is anti with a torsion angle of ±90 to ±180°.

Corresponding to this definition, the conformation of the cyclo­propyl group relative to the nucleobase is anti with the torsion angle C19—C18—C7—C5 = 166.0 (2)°, and the cyclo­propyl group points away from the nucleobase. For the full anti conformation, a torsion angle of 150° would be expected. This results from a torsion angle of 180° for the ideal anti conformation minus 30° from the cyclo­propane ring.

The bond lengths of the cyclo­propyl group are in the expected range of around 1.51 Å, namely C18—C19 = 1.499 (3) Å, C18—C20 = 1.506 (3) Å and C19—C20 = 1.491 (4) Å. The length of the C7—C18 bond, connecting the cyclo­propyl substituent to the nucleobase, is 1.482 (3) Å, while the corresponding bond of (III) is shorter [1.427 (3) Å; Seela et al., 2006].

In the solid-state structure of nucleoside (I), the individual molecules are stacked into columns and arranged into layers which are highly ordered. Within each layer, the nucleosides form rows with a reverse head-to-tail arrangement of the molecules. Consequently, the heterocyclic ring of one molecule faces the sugar residue of a neighbouring molecule (Fig. 2).

Each layer is stabilized by inter­molecular hydrogen bonds which are formed between the amino group and the sugar residue, and the heterocyclic ring and the sugar residue, as well as between neighbouring sugar residues. Most inter­estingly, atom O5' as acceptor forms a bifurcated hydrogen bond to the amino groups of two different neighbouring molecules acting as donors (N6—H6A···O5'ⁱ and N6—H6B···O5'ⁱⁱ; see Table 3 for symmetry codes and geometry). By this means, four neighbouring molecules form a rhomboidal arrangement of two bifurcated hydrogen bonds, involving two amino groups and two O5' atoms of the sugar residues (Fig. 2).

In addition, the layers are stabilized by a hydrogen bond between atom O3' of the hy­droxy group as acceptor and the O3'—H3' group of a neighbouring molecule as donor (O3'—H3'O···O3'ⁱⁱⁱ), as well as by a contact between a sugar residue and a heterocycle, involving atom N1 of the 7-de­aza­purine group as acceptor and the O5'—H5'O group of the sugar residue as donor (O5'—H5'O···N1^iv).

A weak contact (Steiner, 2002) is observed between the C19—H19A group of the 7-cyclo­propyl substituent as donor and atom N1 of a neighbouring nucleobase as acceptor (C19—H19A···N3). This contact probably stabilizes the anti orientation of the cyclo­propyl group with respect to the 7-de­aza­purine heterocycle.

Related literature

For related literature, see: Abola & Sundaralingam (1973); Altona & Sundaralingam (1972); Anzai et al. (1957); Arnott & Hukins (1972); Barrett & Kasdorf (1996); Bergstrom et al. (1984); Brackmann & de Meijere (2007); Charette & Lebel (1996); Chen et al. (2010); De Clercq, Bernaerts, Bergstrom, Robins, Montgomery & Holy (1986); Eldrup (2004); Flack (1983); Franck-Neumann, Sedrati, Vigneron & Bloy (1985); IUPAC–IUB (1983); Kuchař et al. (2008); Olsen (2004); Peters et al. (1992); Rosemeyer et al. (1997); Saenger (1984); Seela et al. (2005, 2006, 2007, 2008); Sekiyama et al. (1998); Sheldrick (2008); Steiner (2002); Stroud (1973); Suhadolnik (1970); Van Wijk, Haasnoot, de Leeuw, Huckriede, Westra Hoekzema & Altona (1999); Vince & Hua (1990, 2006); Zabel et al. (1987); de Meijere (1979).

Computing details

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. A perspective view of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. A detailed view of the hydrogen-bonded (dashed lines) network of (I) within one layer. The projection is parallel to the bc plane.

4-Amino-5-cyclopropyl-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine

Crystal data

C14H18N4O3	F(000) = 616
Mr = 290.32	Dx = 1.415 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9734 reflections
a = 5.0104 (3) Å	θ = 2.7–25.5°
b = 13.0418 (7) Å	µ = 0.10 mm^−1
c = 20.8610 (9) Å	T = 130 K
V = 1363.15 (12) Å^3	Needle, colourless
Z = 4	0.50 × 0.24 × 0.14 mm

Data collection

Bruker APEXII CCD area-detector diffractometer	3302 independent reflections
Radiation source: fine-focus sealed tube	2963 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.094
ϕ and ω scans	θmax = 28.0°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −6→6
Tmin = 0.951, Tmax = 0.986	k = −17→17
43772 measured reflections	l = −27→27

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.040	w = 1/[σ^2(Fo^2) + (0.0494P)^2 + 0.4866P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.098	(Δ/σ)max < 0.001
S = 1.09	Δρmax = 0.32 e Å^−3
1942 reflections	Δρmin = −0.26 e Å^−3
193 parameters	Extinction correction: SHELXTL (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.011 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: established by known chemical absolute configuration
Secondary atom site location: difference Fourier map

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.5206 (4)	0.67585 (13)	0.35671 (8)	0.0188 (4)
C2	0.5135 (5)	0.64964 (16)	0.29414 (10)	0.0194 (4)
H2	0.6277	0.5950	0.2817	0.023*
N3	0.3665 (4)	0.69090 (13)	0.24787 (8)	0.0181 (4)
C4	0.2115 (4)	0.76770 (15)	0.26944 (9)	0.0157 (4)
C5	0.1955 (4)	0.80313 (15)	0.33284 (9)	0.0147 (4)
C6	0.3639 (5)	0.75341 (15)	0.37694 (10)	0.0162 (4)
N6	0.3733 (4)	0.77712 (14)	0.44023 (8)	0.0209 (4)
H6A	0.4786	0.7424	0.4661	0.025*
H6B	0.2742	0.8272	0.4554	0.025*
C7	0.0037 (5)	0.88489 (15)	0.33443 (10)	0.0168 (4)
C8	−0.0853 (5)	0.89580 (16)	0.27312 (10)	0.0185 (5)
H8	−0.2135	0.9449	0.2596	0.022*
N9	0.0385 (4)	0.82472 (13)	0.23304 (8)	0.0165 (4)
C18	−0.0696 (5)	0.94691 (16)	0.39131 (10)	0.0206 (5)
H18	−0.1072	0.9070	0.4312	0.025*
C19	−0.2242 (6)	1.04462 (18)	0.38400 (11)	0.0305 (6)
H19A	−0.2758	1.0657	0.3401	0.037*
H19B	−0.3557	1.0619	0.4177	0.037*
C20	0.0644 (6)	1.04903 (19)	0.40124 (13)	0.0351 (7)
H20A	0.1113	1.0689	0.4456	0.042*
H20B	0.1913	1.0727	0.3680	0.042*
C1'	0.0103 (5)	0.81968 (15)	0.16412 (9)	0.0154 (4)
H1'	0.1097	0.7590	0.1472	0.018*
C2'	−0.2757 (4)	0.81800 (16)	0.13952 (9)	0.0166 (4)
H2'A	−0.3934	0.8611	0.1665	0.020*
H2'B	−0.3470	0.7472	0.1384	0.020*
C3'	−0.2496 (4)	0.86227 (14)	0.07177 (9)	0.0134 (4)
H3'A	−0.3989	0.9110	0.0627	0.016*
O3'	−0.2328 (3)	0.78587 (11)	0.02252 (7)	0.0172 (3)
H3'O	−0.3872	0.7679	0.0116	0.026*
C4'	0.0193 (4)	0.91947 (14)	0.07334 (9)	0.0129 (4)
H4'A	0.1466	0.8841	0.0438	0.016*
O4'	0.1199 (3)	0.91218 (11)	0.13765 (7)	0.0167 (3)
C5'	0.0010 (5)	1.03113 (15)	0.05444 (10)	0.0186 (4)
H5'C	−0.1094	1.0373	0.0153	0.022*
H5'B	−0.0891	1.0698	0.0891	0.022*
O5'	0.2556 (4)	1.07539 (11)	0.04281 (7)	0.0216 (4)
H5'O	0.3167	1.0994	0.0772	0.032*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0204 (10)	0.0193 (8)	0.0168 (8)	0.0034 (8)	−0.0020 (8)	0.0028 (7)
C2	0.0177 (11)	0.0199 (9)	0.0207 (10)	0.0039 (9)	0.0004 (9)	−0.0001 (8)
N3	0.0197 (10)	0.0195 (8)	0.0150 (8)	0.0039 (8)	−0.0003 (7)	−0.0004 (7)
C4	0.0157 (11)	0.0160 (9)	0.0154 (9)	−0.0022 (8)	0.0001 (8)	0.0019 (7)
C5	0.0156 (11)	0.0142 (9)	0.0145 (9)	−0.0019 (8)	−0.0001 (8)	0.0008 (7)
C6	0.0172 (11)	0.0151 (9)	0.0163 (10)	−0.0019 (8)	−0.0015 (8)	0.0028 (7)
N6	0.0280 (11)	0.0190 (8)	0.0157 (8)	0.0051 (8)	−0.0042 (8)	0.0006 (7)
C7	0.0185 (11)	0.0150 (9)	0.0169 (9)	0.0001 (9)	0.0008 (9)	0.0012 (7)
C8	0.0198 (12)	0.0191 (9)	0.0165 (9)	0.0049 (9)	0.0002 (8)	0.0008 (8)
N9	0.0173 (10)	0.0188 (8)	0.0136 (8)	0.0053 (7)	−0.0020 (7)	0.0002 (6)
C18	0.0277 (13)	0.0204 (10)	0.0137 (10)	0.0074 (10)	0.0003 (9)	0.0014 (8)
C19	0.0462 (17)	0.0279 (11)	0.0175 (10)	0.0194 (13)	−0.0026 (11)	−0.0024 (9)
C20	0.0493 (19)	0.0268 (12)	0.0291 (13)	0.0014 (13)	−0.0045 (13)	−0.0103 (10)
C1'	0.0165 (10)	0.0179 (9)	0.0117 (9)	0.0024 (9)	−0.0005 (8)	0.0000 (7)
C2'	0.0133 (10)	0.0221 (9)	0.0143 (9)	−0.0015 (9)	−0.0002 (8)	0.0008 (8)
C3'	0.0117 (9)	0.0144 (8)	0.0140 (9)	0.0016 (8)	−0.0008 (8)	−0.0018 (7)
O3'	0.0120 (8)	0.0221 (7)	0.0175 (7)	−0.0008 (7)	−0.0021 (6)	−0.0088 (5)
C4'	0.0110 (10)	0.0159 (8)	0.0119 (8)	0.0002 (8)	−0.0005 (8)	−0.0010 (7)
O4'	0.0149 (7)	0.0201 (7)	0.0152 (7)	−0.0029 (6)	−0.0050 (6)	0.0028 (6)
C5'	0.0208 (11)	0.0157 (9)	0.0192 (10)	−0.0011 (9)	−0.0063 (10)	0.0018 (8)
O5'	0.0275 (9)	0.0219 (7)	0.0155 (7)	−0.0112 (7)	−0.0029 (7)	0.0016 (6)

Geometric parameters (Å, º)

N1—C6	1.348 (3)	C19—H19A	0.9900
N1—C2	1.350 (3)	C19—H19B	0.9900
C2—N3	1.328 (3)	C20—H20A	0.9900
C2—H2	0.9500	C20—H20B	0.9900
N3—C4	1.345 (3)	C1'—O4'	1.436 (2)
C4—N9	1.371 (3)	C1'—C2'	1.522 (3)
C4—C5	1.403 (3)	C1'—H1'	1.0000
C5—C6	1.407 (3)	C2'—C3'	1.532 (3)
C5—C7	1.436 (3)	C2'—H2'A	0.9900
C6—N6	1.357 (3)	C2'—H2'B	0.9900
N6—H6A	0.8800	C3'—O3'	1.434 (2)
N6—H6B	0.8800	C3'—C4'	1.541 (3)
C7—C8	1.362 (3)	C3'—H3'A	1.0000
C7—C18	1.482 (3)	O3'—H3'O	0.8400
C8—N9	1.394 (3)	C4'—O4'	1.436 (2)
C8—H8	0.9500	C4'—C5'	1.511 (3)
N9—C1'	1.446 (2)	C4'—H4'A	1.0000
C18—C19	1.499 (3)	C5'—O5'	1.421 (3)
C18—C20	1.506 (3)	C5'—H5'C	0.9900
C18—H18	1.0000	C5'—H5'B	0.9900
C19—C20	1.491 (4)	O5'—H5'O	0.8400
C6—N1—C2	118.53 (18)	C19—C20—H20A	117.8
N3—C2—N1	127.9 (2)	C18—C20—H20A	117.8
N3—C2—H2	116.0	C19—C20—H20B	117.8
N1—C2—H2	116.0	C18—C20—H20B	117.8
C2—N3—C4	112.26 (18)	H20A—C20—H20B	114.9
N3—C4—N9	125.69 (18)	O4'—C1'—N9	107.86 (16)
N3—C4—C5	126.41 (19)	O4'—C1'—C2'	104.04 (16)
N9—C4—C5	107.89 (18)	N9—C1'—C2'	115.34 (18)
C4—C5—C6	115.48 (19)	O4'—C1'—H1'	109.8
C4—C5—C7	107.73 (18)	N9—C1'—H1'	109.8
C6—C5—C7	136.78 (19)	C2'—C1'—H1'	109.8
N1—C6—N6	117.09 (19)	C1'—C2'—C3'	103.03 (17)
N1—C6—C5	119.37 (18)	C1'—C2'—H2'A	111.2
N6—C6—C5	123.5 (2)	C3'—C2'—H2'A	111.2
C6—N6—H6A	120.0	C1'—C2'—H2'B	111.2
C6—N6—H6B	120.0	C3'—C2'—H2'B	111.2
H6A—N6—H6B	120.0	H2'A—C2'—H2'B	109.1
C8—C7—C5	105.96 (18)	O3'—C3'—C2'	113.84 (16)
C8—C7—C18	127.9 (2)	O3'—C3'—C4'	107.47 (16)
C5—C7—C18	126.13 (19)	C2'—C3'—C4'	103.73 (15)
C7—C8—N9	110.38 (19)	O3'—C3'—H3'A	110.5
C7—C8—H8	124.8	C2'—C3'—H3'A	110.5
N9—C8—H8	124.8	C4'—C3'—H3'A	110.5
C4—N9—C8	108.03 (16)	C3'—O3'—H3'O	109.5
C4—N9—C1'	125.99 (18)	O4'—C4'—C5'	109.20 (16)
C8—N9—C1'	125.67 (18)	O4'—C4'—C3'	107.15 (15)
C7—C18—C19	120.69 (18)	C5'—C4'—C3'	114.07 (18)
C7—C18—C20	118.8 (2)	O4'—C4'—H4'A	108.8
C19—C18—C20	59.51 (18)	C5'—C4'—H4'A	108.8
C7—C18—H18	115.4	C3'—C4'—H4'A	108.8
C19—C18—H18	115.4	C1'—O4'—C4'	106.29 (15)
C20—C18—H18	115.4	O5'—C5'—C4'	112.43 (19)
C20—C19—C18	60.47 (17)	O5'—C5'—H5'C	109.1
C20—C19—H19A	117.7	C4'—C5'—H5'C	109.1
C18—C19—H19A	117.7	O5'—C5'—H5'B	109.1
C20—C19—H19B	117.7	C4'—C5'—H5'B	109.1
C18—C19—H19B	117.7	H5'C—C5'—H5'B	107.9
H19A—C19—H19B	114.8	C5'—O5'—H5'O	109.5
C19—C20—C18	60.02 (17)
C6—N1—C2—N3	−0.5 (4)	C7—C8—N9—C1'	−174.3 (2)
N1—C2—N3—C4	0.2 (3)	C8—C7—C18—C19	−10.9 (4)
C2—N3—C4—N9	−180.0 (2)	C5—C7—C18—C19	166.0 (2)
C2—N3—C4—C5	−0.6 (3)	C8—C7—C18—C20	−80.6 (3)
N3—C4—C5—C6	1.3 (3)	C5—C7—C18—C20	96.3 (3)
N9—C4—C5—C6	−179.26 (18)	C7—C18—C19—C20	−107.5 (3)
N3—C4—C5—C7	−179.3 (2)	C7—C18—C20—C19	110.6 (2)
N9—C4—C5—C7	0.1 (2)	C4—N9—C1'—O4'	−108.7 (2)
C2—N1—C6—N6	179.3 (2)	C8—N9—C1'—O4'	64.2 (3)
C2—N1—C6—C5	1.1 (3)	C4—N9—C1'—C2'	135.6 (2)
C4—C5—C6—N1	−1.5 (3)	C8—N9—C1'—C2'	−51.6 (3)
C7—C5—C6—N1	179.3 (2)	O4'—C1'—C2'—C3'	36.62 (19)
C4—C5—C6—N6	−179.5 (2)	N9—C1'—C2'—C3'	154.54 (16)
C7—C5—C6—N6	1.3 (4)	C1'—C2'—C3'—O3'	96.77 (19)
C4—C5—C7—C8	−0.4 (2)	C1'—C2'—C3'—C4'	−19.70 (19)
C6—C5—C7—C8	178.8 (3)	O3'—C3'—C4'—O4'	−124.34 (16)
C4—C5—C7—C18	−177.8 (2)	C2'—C3'—C4'—O4'	−3.47 (19)
C6—C5—C7—C18	1.4 (4)	O3'—C3'—C4'—C5'	114.68 (18)
C5—C7—C8—N9	0.5 (3)	C2'—C3'—C4'—C5'	−124.45 (18)
C18—C7—C8—N9	177.9 (2)	N9—C1'—O4'—C4'	−163.04 (17)
N3—C4—N9—C8	179.6 (2)	C2'—C1'—O4'—C4'	−40.08 (19)
C5—C4—N9—C8	0.2 (2)	C5'—C4'—O4'—C1'	151.19 (18)
N3—C4—N9—C1'	−6.5 (4)	C3'—C4'—O4'—C1'	27.2 (2)
C5—C4—N9—C1'	174.1 (2)	O4'—C4'—C5'—O5'	73.1 (2)
C7—C8—N9—C4	−0.4 (3)	C3'—C4'—C5'—O5'	−167.09 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6A···O5′^i	0.88	2.56	3.241 (2)	135
N6—H6B···O5′^ii	0.88	2.23	2.949 (2)	139
O3′—H3′O···O3′^iii	0.84	2.00	2.8344 (12)	173
O5′—H5′O···N1^iv	0.84	1.89	2.715 (2)	168
C19—H19A···N3^v	0.99	2.50	3.423 (3)	155

Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) −x+1/2, −y+2, z+1/2; (iii) x−1/2, −y+3/2, −z; (iv) −x+1, y+1/2, −z+1/2; (v) −x, y+1/2, −z+1/2.