Tautomeric 6 oxoisocytidine (methanol solvate)

(1)

Acta Cryst.(2002). E58, o1031±o1033 DOI: 10.1107/S1600536802015040 Swenson, Bera and Nair C₉H₁₃N₃O₅CH₄O

o1031

organic papers

Acta Crystallographica Section E Structure Reports

Online

ISSN 1600-5368

Tautomeric 6-oxoisocytidine (methanol solvate)

Dale C. Swenson,* Sanjib Bera and Vasu Nair

Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA

Correspondence e-mail: dale-swenson@uiowa.edu

Key indicators

Single-crystal X-ray study T= 180 K

Mean(C±C) = 0.006 AÊ Disorder in main residue Rfactor = 0.052 wRfactor = 0.128 Data-to-parameter ratio = 6.0

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

Ambiguity concerning the base structure of 6-oxoisocytidine methanol solvate {systematic name: 4-(R )-[4-amino-2,6-dioxo-pyrimidine-1-yl]-3(S)-hydroxy-2(R)-furanmethanol methanol solvate}, C18H18N18O18CH3OH, is resolved by the crystal

structure reported here. The 3-imine N site is protonated and forms a hydrogen bond with the 6-oxo carbonyl group of an adjacent molecule. The solid-state packing leads to the formation of sheets of molecules with the intervening space occupied by disordered methanol solvent molecules.

Comment

Isomeric nucleosides (or isonucleosides), a novel class of nucleosides, have attracted much interest recently because of their signi®cant anti-HIVand anti-HSVactivity, as well as their stability towards acidic and enzymatic deamination (Nair & Jahnke, 1995). For example, 4(S)-(6-amino-9H -purin-9-yl)-tetrahydro-1(S)-furanmethanol (IsoddA), an isomeric di-deoxynucleoside synthesized in our laboratory, has antiviral activity against HIV-1 and HIV-2 (Nair et al., 1995; Nair & Nuesca, 1992). In addition, it has been reported that the iso-deoxynucleoside, IsodG, with guanine as the nucleobase, has activity against HSV-1 and HSV-2 (Kakefudaet al., 1994). Our interest in isomeric nucleosides with new nucleobases led us to the synthesis of 6-oxoisocytidine, (I). However, in the litera-ture, there is some ambiguity concerning the structure of the base moiety of 6-oxocytidine. Two different structures have been suggested for this base moiety in compounds (II) (Falco

et al., 1970) and (III) (Lipkin et al., 1968). Thus, it was important, not only to synthesize compound (I) for antiviral studies, to establish unequivocally the structure of the target molecule by physicochemical techniques including single-crystal X-ray single-crystallography. The target nucleoside, (I), was synthesized from 5-iodoisocytidineviathe anhydronucleoside intermediate.

The furanose ring adopts a C20_{-envelope conformation. The}

envelope (O10_/C30_/C40_/C50_{) is nearly perpendicular [dihedral}

angle = 89.5 (2)_{] to the planar cytidine ring (N1/C2/N3/C4/}

C5/C6; r.m.s. deviation = 0.003 AÊ). The CH2OH equatorial

(2)

substituent at C20_{exhibits threefold disorder, with each of the}

C20_ÐC60_anti_{conformers equally represented. [The C6}0_ÐO60

orientation isantito C20_ÐC30_{(site 1), C6}0_B_ÐO60_B_is_anti_to

C20_ÐO10_{(site 2), and C6}0_C_ÐO60_C_is _anti_{to C2}0_ÐH20_{1 (site}

3).]

The H3 O6 and H4B O6 hydrogen bonds form ribbons of molecules parallel to thebaxis. These ribbons stack parallel to theaaxis to form sheets. The stacks are held togethervia -stacking interactions [cytidine±cytidinei _{= 3.419 AÊ and}

cyti-dine±cytidineii_{= 3.333 AÊ; symmetry codes: (i) 1}_ÿ_x_,_ÿ_y_,1 2+z;

(ii) 2ÿx,ÿy,1

2+z] and the H4A O30hydrogen bond. The

inter-sheet space [centered on the (x,y, 0) and (x,y,1

2) planes]

is occupied by disordered methanol of solvation. Four partially occupied [occ(C21ÐO21) = 0.333, occ(C210_±O210_{) = 0.333,}

occ(C31ÐO31) = 0.166 and occ(C310_ÐO310_{) = 0.166] sites are}

included in the structure. The O30_ÐH30 _{hydroxyl group}

hydrogen bonds to the methanol O atom (for each of the disorder sites). There is a correlation between the location of the >C20_ÐCH

2OH substituent and the methanol disorder

sites. For site 1, the methanol molecule is located at the C31Ð O31 and C310_ÐO310_{sites, for site 2 at the C21}0_ÐO210_{site, and}

for site 3 at the C21ÐO21 site. See Table 2 for the

hydrogen-bonding geometries (including the disordered structure). The conclusion from the X-ray data is supported by the high-®eld13_{C NMR spectrum.}

Experimental

Compound (I): to a solution of 5-iodoisocytidine (0.36 g, 1 mmol) in DMSO/t_{BuOH (1:1, 40 ml) was added}t_{BuOK (0.45 g, 4 mmol). The} reaction mixture was heated at 333 K for 24 h. The solution was neutralized with 0.5M aqueous HCl, evaporated to dryness and puri®ed over silica gel to give the anhydro derivative. The anhydro derivative was dissolved in 0.2M Ba(OH)2(10 ml) and heated at

373 K for 1 h. The solution was neutralized with 0.5M HCl and evaporated to dryness. The residue was puri®ed over HPLC on C-18 reverse-phase column (H2O/MeOH) to give (I) (0.04 g, 16%) as a

white powder. Compound (I) was crystallized from MeOH (m.p. 454 K). 1_{H NMR (DMSO-}_d

6, p.p.m.): 10.40 (bs, 1 H); 13C NMR

(DMSO-d6, p.p.m.): 163.3, 153.8, 151.1, 85.0, 74.2, 71.2, 65.3, 61.9, 57.7;

UV (MeOH): max 266; HRMS (FAB): (M + H)+ calculated for

C9H14N3O5244.0933, found 244.0923.

Crystal data

C9H13N3O5CH4O

Mr= 275.27

Orthorhombic,C2221

a= 6.7571 (14) AÊ

b= 12.430 (3) AÊ

c= 28.880 (6) AÊ

V= 2425.7 (9) AÊ3

Z= 8

Dx= 1.507 Mg mÿ3

MoKradiation

Cell parameters from 4008 re¯ections

= 3.3±25.0

= 0.13 mmÿ1

T= 180 (2) K

Plate, colorless

0.130.110.03 mm

Data collection

Nonius KappaCCD diffractometer

CCD'scans

Absorption correction: none 13 640 measured re¯ections 1237 independent re¯ections 1078 re¯ections withI> 2(I)

Rint= 0.058 max= 25.0

h=ÿ8!8

k=ÿ14!14

l=ÿ34!34

Re®nement

Re®nement onF2

R[F2_{> 2}₍_F2_{)] = 0.052}

wR(F2_{) = 0.128}

S= 1.06 1231 re¯ections 206 parameters

H atoms treated by a mixture of independent and constrained re®nement

w= 1/[2₍_F

o2) + (0.0581P)2 + 4.8516P]

whereP= (Fo2+ 2Fc2)/3 (/)max= 0.034

max= 0.20 e AÊÿ3

min=ÿ0.26 e AÊÿ3

Extinction correction:SHELXTL

Extinction coef®cient: 0.0091 (16)

Table 1

Selected geometric parameters (AÊ,_).

N1ÐC2 1.399 (5)

N1ÐC6 1.417 (5)

N1ÐC40 _{1.483 (5)}

C2ÐN3 1.354 (5)

N3ÐC4 1.364 (5)

C4ÐN4 1.350 (5)

C4ÐC5 1.381 (6)

C5ÐC6 1.396 (5)

O10_ÐC20 _{1.423 (6)}

O10_ÐC50 _{1.442 (6)}

C30_ÐC20 _{1.491 (7)}

C30_ÐC40 _{1.557 (7)}

C40_ÐC50 _{1.509 (7)}

C2ÐN1ÐC6 122.8 (3)

C2ÐN1ÐC40 _{118.1 (3)}

C6ÐN1ÐC40 _{119.0 (3)}

N3ÐC2ÐN1 114.9 (3)

C2ÐN3ÐC4 125.4 (3)

N3ÐC4ÐC5 119.7 (4)

C4ÐC5ÐC6 119.1 (4)

C5ÐC6ÐN1 118.1 (3)

C20_ÐO10_ÐC50 _{106.1 (4)}

C20_ÐC30_ÐC40 _{100.2 (4)}

N1ÐC40_ÐC50 _{115.5 (4)}

N1ÐC40_ÐC30 _{115.3 (4)}

C50_ÐC40_ÐC30 _{104.6 (3)}

O10_ÐC50_ÐC40 _{107.3 (4)}

O10_ÐC20_ÐC30 _{106.6 (4)}

Figure 1

View of the title compound. Displacement ellipsoids are shown at the 35% probability level. Only one orientation of the disordered CH2OH

(3)

Table 2

Hydrogen-bonding geometry (AÊ,_).

DÐH A DÐH H A D A DÐH A

N3ÐH3 O6i _0.88 _1.90 _{2.724 (4)} ₁₅₅

N4ÐH4A O30ii _0.88 _2.08 _{2.898 (5)} ₁₅₅

N4ÐH4B O6i _0.88 _2.10 _{2.858 (5)} ₁₄₄

O60_ÐH60_O31iii _0.84 _2.18 _{2.57 (3)} ₁₀₈

O60_ÐH60_O310iii _0.84 _2.30 _{2.85 (5)} ₁₂₃

O60_B_ÐH60_B_O2iv _0.84 _2.05 _{2.793 (12)} ₁₄₇

O60_C_ÐH60_C_N4v _0.84 _2.35 _{3.041 (10)} ₁₄₀

O60_C_ÐH60_C_O10 _0.84 _2.32 _{2.786 (12)} ₁₁₅

O30_ÐH30_O21vi _0.84 _1.88 _{2.722 (12)} ₁₇₅

O30_ÐH30_O210vi _0.84 _2.11 _{2.936 (13)} ₁₇₀

O30_ÐH30_O31vii _0.84 _1.72 _{2.55 (2)} ₁₆₈

O30_ÐH30_O310vii _0.84 _2.07 _{2.75 (15)} ₁₃₇

O21ÐH21 O10viii _0.84 _2.02 _{2.856 (13)} ₁₇₃

O210_ÐH210_O60_B _0.84 _1.94 _{2.68 (2)} ₁₄₇

O31ÐH31 O10ix _0.84 _2.11 _{2.851 (15)} ₁₄₆

O310_ÐH310_O60 _0.84 _2.22 _{2.81 (2)} ₁₂₈

Symmetry codes: (i)3

2ÿx;12y;12ÿz; (ii) 1ÿx;y;12ÿz; (iii)12x;12ÿy;1ÿz; (iv) xÿ1

2;yÿ12;z; (v) 32ÿx;yÿ12;12ÿz; (vi) 12x;12y;z; (vii) x;1ÿy;1ÿz; (viii) xÿ1;y;z; (ix)xÿ1

2;12ÿy;1ÿz.

The CH2OH substituent at C20is disordered, by rotation about the

C20_ÐC60_{bond, over three orientations of equal occupancy (0.3333).}

In one orientation (C60_/H60_1/H60_2/O60_/H60_{), the CÐO bond is}_anti_to

the C20_ÐC30 _{bond, another (C6}0_B_/H60_3/H60_4/O60_B_/H60_B_{) has the}

CÐO bondantito the C20_ÐO10_{bond, and the third (C6}0_C_/H60_5/H60_6/

O60_C_/H60_C_{) has the CÐO bond} _anti _{to the C2}0_ÐH20_{1 bond. The}

occupancies of each re®ned to approximately 1/3, so each was ®xed to 0.3333 for the ®nal re®nement cycles. The coordinates of H20_{1 were}

allowed to re®ne with a Uiso value of 1.1Ueq(C20). The methanol

molecule of solvation is also disordered and each orientation was re®ned as a rigid group (CÐH = 0.99 AÊ, CÐO = 1.45 AÊ and OÐH = 0.84 AÊ, tetrahedral angles). One orientation (C21/H21AÐC/O21/ H21) was re®ned with occupancy 0.3333, as was the second (C210_/

H21DÐF/O210_/H210_{). For these two orientations, the C and O atoms}

were re®ned with individual isotropic displacement parameters. The third orientation exhibited high thermal motion and was split into two groups (C31/H31AÐC/O31/H31 and C310_/H31_D_ÐF/O310_/H310_{) with}

occupancy 0.1666 and one isotropic displacement parameter for both C and both O atoms. All H atoms (except H20_{1) were included with}

the riding model (or were part of a rigid group) with program defaults. The largest shift (0.034) occurred for the rotz parameter of the O31 rigid group. The average shift was 0.003. 433 Friedel pairs were merged for the ®nal cycles of re®nement. The absolute structure was assumed from the synthesis.

Data collection:COLLECT(Nonius, 1997±2000); cell re®nement: HKL SCALEPACK(Otwinowski & Minor, 1997); data reduction: HKL DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to re®ne structure:SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

This research was supported by the National Institutes of Health (NIAID), grant number ROI A132851.

References

Falco, E. A., Otter, B. A. & Fox, J. J. (1970).J. Org. Chem.35, 2326±2330. Kakefuda, A., Shuto, S., Nagahata, T., Seki, J., Sasaki, T. & Matsuda, A. (1994).

Tetrahedron,50, 10167±10182.

Lipkin, D., Cori, C. & Sano, M. (1968).Tetrahedron Lett.pp. 5993±5996. Nair, V. & Jahnke, T. S. (1995).Antimicrob. Agents Chemother.39, 1017±1029. Nair, V. & Nuesca, Z. M. (1992).J. Am. Chem. Soc.114, 7951±7953. Nair, V., St Clair, M., Reardon, J. E., Krasny, H. C., Hazen, R. J., Paff, M. T.,

Boone, L. R., Tisdale, M., Najera, I., Dornsife, R. E., Everett, D. R., Borroto-Esoda, K., Yale, J. L., Zimmerman, T. P. & Rideout, J. L. (1995).

Antimicrob. Agents Chemother.39, 1993±1999.

Nonius (1997±2000).COLLECT. Nonius BV, Delft, The Netherlands.

Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,

Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307±326. New York: Academic Press.

Sheldrick, G. M. (1997).SHELXTL.Version 5.1. Siemens Analytical X-ray

Instruments Inc., Madison, Wisconsin, USA.

(4)

supporting information

Acta Cryst. (2002). E58, o1031–o1033 [doi:10.1107/S1600536802015040]

Tautomeric 6-oxoisocytidine (methanol solvate)

Dale C. Swenson, Sanjib Bera and Vasu Nair

S1. Comment

Isomeric nucleosides (or isonucleosides), a novel class of nucleosides, have attracted much interest recently because of

their significant anti-HIV and anti-HSV activity, as well as their stability towards acidic and enzymatic deamination (Nair

& Jahnke, 1995). For example, 4(S)-(6-amino-9H-purin-9-yl)-tetrahydro-1(S)-furanmethanol (IsoddA), an isomeric

di-deoxynucleoside synthesized in our laboratory, has antiviral activity against HIV-1 and HIV-2 (Nair et al., 1995; Nair &

Nuesca, 1992). In addition, it has been reported that the isodeoxynucleoside, IsodG, with guanine as the nucleobase, has

activity against HSV-1 and HSV-2 (Kakefuda et al., 1994). Our interest in isomeric nucleosides with new nucleobases led

us to the synthesis 6-oxoisocytidine (I). However, in the literature, there is some ambiguity about the structure of the base

moiety of 6-oxocytidine. Two different structures have been suggested for this base moiety in compounds (II) (Falco et

al., 1970) and (III) (Lipkin et al., 1968). Thus, it was important, not only to synthesize compound (I) for antiviral studies,

but, prior to those biological studies, it was important to establish unequivocally the structure of the target molecule by

physicochemical techniques including single-crystal X-ray data. The target nucleoside (I) was synthesized from

5-iodo-isocytidine via anhydronucleoside intermediate.

The furanose ring adopts a C2′-envelope conformation. The envelope (O1′/C3′/C4′/C5′) is nearly perpendicular

[dihedral angle = 89.5 (2)°] to the planar cytidine ring (N1/C2/N3/C4/C5/C6; r.m.s. deviation = 0.003 Å). The CH2OH

equitorial substituent at C2′ exhibits threefold disorder, with each of the C2′–C6′ anti conformers equally represented.

[The C6′—O6′ orientation is anti to C2′—C3′ (site 1), C6′B—O6′B is anti to C2′—O1′ (site 2), and C6′C—O6′C is anti to

C2′—H2′1 (site 3).]

The H3···O6 and H4B···O6 hydrogen bonds form ribbons of molecules parallel to the b axis. These ribbons stack

parallel to the a axis to form sheets. The stacks are held together viaπ-stacking interactions [cytidine–cytidinei_{= 3.419 Å}

and cytidine–cytidineii_{= 3.333 Å; symmetry codes: (i) 1 −}_x_{, −}_y_{, 0.5 +}_z_{; (ii) 2 −}_x_{, −}_y_{, 0.5 +}_z_{] and the H4A···O3′}

hydrogen bond. The inter-sheet space [centered on the (x, y, 0) and (x, y, 1/2) planes] is occupied by disordered methanol

of solvation. Four partially occupied [occ(C21—O21) = 1/3, occ(C21′-O21′) = 1/3, occ(C31—O31) = 0.166 and

occ(C31′-O31′) = 0.166] sites are included in the structure. The O3′—H3′ hydroxyl group hydrogen bonds to the

methanol O atom (for each of the disorder sites). There is a correlation between the location of the >C2′—CH2OH

substituent and the methanol disorder sites. For site 1, the methanol molecule is located at the C31—O31 and C31′—O31

sites, for site 2 at the C21′—O21′ site, and for site 3 at the C21—O21 site. See Table 3 for the hydrogen-bonding

geometries (including the disordered structure).

The conclusion from the X-ray data is supported by the high-field 13_{C NMR spectrum.}

S2. Experimental

Compound A: to a solution of 5-iodoisocytidine (0.36 g, 1 mmol) in DMSO/t-BuOH (1:1, 40 ml) was added t-BuOK

(5)

supporting information

sup-2

Acta Cryst. (2002). E58, o1031–o1033

HCl, evaporated to dryness and purified over silica gel to give the anhydro derivative. The anhydro derivative was

dissolved in 0.2 M Ba(OH)2 (10 ml) and heated at 373 K for 1 h. The solution was neutralized with 0.5 M HCl and

evaporated to dryness. The residue was purified over HPLC on C-18 reverse-phase column (H2O/MeOH) to give A (0.04

g, 16%) as a white powder. Compound A was crystallized from MeOH (m.p. 454 K). 1_{H NMR (DMSO-d}

6, p.p.m.): 10.40

(bs, 1H); 13_{C NMR (DMSO-d}

6, p.p.m.): 163.3, 153.8, 151.1, 85.0, 74.2, 71.2, 65.3, 61.9, 57.7; UV (MeOH): λmax 266;

HRMS (FAB): (M + H)+_{calculated for C}

9H14N3O5 244.0933, found 244.0923.

S3. Refinement

The CH2OH substituent at C2′ is disordered by rotation about the C2′—C6′ bond to three orientations of equal occupancy

(1/3). In one orientation (C6′/H6′1/H6′2/O6′/H6′), the C—O bond is anti to the C2′—C3′ bond, another

(C6′B/H6′3/H6′4/O6′B/H6′B) has the C—O bond anti to the C2′—O1′ bond, and the third (C6′C/H6′5/H6′6/O6′C/H6′C)

has the C—O bond anti to the C2′—H2′1 bond. The occupancies of each refined to approximately 1/3 so each was fixed

to 0.3333 for the final refinement cycles. The coordinates of H2′1 were allowed to refine with a Uiso vale of 1.1Uiso(C2′).

The methanol molecule of solvation is also disordered and each orientation was refined as a rigid group (C—H = 0.99 Å,

C—O = 1.45 Å and O—H = 0.84 Å, tetrahedral angles). One orientation (C21/H21A—C/O21/H21) was refined with

occupancy 0.3333 as was the second (C21′/H21D—F/O21′/H21′). For these two orientations, the C and O atoms were

refined with individual isotropic displacement parameters. The third orientation exhibited high thermal motion and was

split into two groups (C31/H31A—C/O31/H31 and C31′/H31D—F/O31′/H31′) with occupancy 0.1666 and one isotropic

displacement parameter for both C and both O atoms. All H atoms (except H2′1) were included with the riding model (or

were part of a rigid group) with program defaults. The largest shift (0.034) occurred for the rotz parameter of the O31

(6)

Figure 1

View of the title compound. Displacement ellipsoids are shown at the 35% probability level. Only one orientation of the

disorder CH2OH group is shown.

4-(R)-[4-amino-2,6-dioxopyrimidine-1-yl]-3(S)-hydroxy-2(R)-furan methanol solvate

Crystal data

C9H13N3O5·CH4O Mr = 275.27

Orthorhombic, C2221 a = 6.7571 (14) Å

b = 12.430 (3) Å

c = 28.880 (6) Å

V = 2425.7 (9) Å3 Z = 8

F(000) = 1168

Dx = 1.507 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 4008 reflections

θ = 3.3–25.0°

(7)

supporting information

sup-4

Acta Cryst. (2002). E58, o1031–o1033 Data collection

Nonius KappaCCD diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

Detector resolution: 9 pixels mm-1

CCD scans

13640 measured reflections

1237 independent reflections 1078 reflections with I > 2σ(I)

Rint = 0.058

θmax = 25.0°, θmin = 3.3°

h = −8→8

k = −14→14

l = −34→34

Refinement

Refinement on F2

Least-squares matrix: full

R[F2_{> 2}_σ₍_F2_{)] = 0.052} wR(F2_{) = 0.128} S = 1.06 1231 reflections 206 parameters 14 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H atoms treated by a mixture of independent and constrained refinement

w = 1/[σ2₍_Fo2_{) + (0.0581}_P₎2_{+ 4.8516}_P_]

where P = (Fo2_{+ 2}_Fc2_)/3

(Δ/σ)max = 0.034

Δρmax = 0.20 e Å−3

Δρmin = −0.26 e Å−3

Extinction correction: SHELXTL, Fc*_{=kFc[1+0.001xFc}2_λ3_/sin(2_θ_)]-1/4

Extinction coefficient: 0.0091 (16) Absolute structure: syn

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. 433 Friedel pairs were averaged during the final cycles of refinement. Disordered methanol solvent molecules refined as rigid groups. H atoms included with the riding model using program defaults.

11 reflections were removed as outliers.

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 (Å2₎

x y z Uiso*/Ueq Occ. (<1)

N1 0.7557 (7) 0.7210 (2) 0.31294 (11) 0.0254 (8) C2 0.7575 (8) 0.8315 (3) 0.30362 (13) 0.0257 (9) O2 0.7638 (6) 0.8993 (2) 0.33402 (9) 0.0337 (8) N3 0.7515 (7) 0.8574 (3) 0.25810 (10) 0.0270 (8)

H3 0.7534 0.9262 0.2509 0.032*

C4 0.7425 (8) 0.7857 (3) 0.22244 (13) 0.0254 (9) N4 0.7335 (7) 0.8274 (3) 0.17932 (11) 0.0322 (9)

H4B 0.7336 0.8976 0.1754 0.039*

H4A 0.7276 0.7844 0.1552 0.039*

C5 0.7424 (8) 0.6766 (3) 0.23169 (13) 0.0275 (10)

H5 0.7386 0.6259 0.2071 0.033*

(8)

O1′ 0.8542 (5) 0.5247 (3) 0.40043 (13) 0.0429 (10) C3′ 0.5742 (7) 0.6229 (4) 0.37870 (16) 0.0270 (11)

H3′1 0.5290 0.5742 0.3533 0.032*

O3′ 0.4135 (5) 0.6871 (2) 0.39306 (11) 0.0325 (8)

H3′ 0.4549 0.7366 0.4103 0.049*

C4′ 0.7601 (8) 0.6860 (3) 0.36203 (13) 0.0285 (10)

H4′1 0.7688 0.7526 0.3814 0.034*

C5′ 0.9328 (8) 0.6156 (4) 0.37540 (18) 0.0357 (13)

H5′2 1.0040 0.5909 0.3474 0.043*

H5′1 1.0265 0.6562 0.3951 0.043*

C2′ 0.6636 (7) 0.5566 (4) 0.41629 (17) 0.0336 (12) H2′1 0.689 (7) 0.578 (4) 0.4466 (7) 0.040*

C6′ 0.557 (4) 0.4481 (14) 0.4244 (8) 0.029 (2) 0.3333

H6′1 0.4127 0.4608 0.4277 0.035* 0.3333

H6′2 0.5774 0.4006 0.3973 0.035* 0.3333

O6′ 0.6292 (15) 0.3976 (7) 0.4644 (3) 0.035 (2) 0.3333

H6′ 0.6675 0.3352 0.4578 0.052* 0.3333

C6′B 0.537 (2) 0.4537 (11) 0.4210 (9) 0.029 (2) 0.3333

H6′3 0.5633 0.4082 0.3936 0.035* 0.3333

H6′4 0.5856 0.4137 0.4484 0.035* 0.3333

O6′B 0.3311 (15) 0.4630 (9) 0.4254 (4) 0.047 (3) 0.3333

H6′B 0.2794 0.4654 0.3990 0.070* 0.3333

C6′C 0.551 (3) 0.4647 (11) 0.4410 (5) 0.029 (2) 0.3333

H6′5 0.6251 0.4403 0.4687 0.035* 0.3333

H6′6 0.4181 0.4888 0.4507 0.035* 0.3333

O6′C 0.5379 (16) 0.3821 (10) 0.4083 (3) 0.039 (3) 0.3333

H6′C 0.6452 0.3773 0.3938 0.059* 0.3333

O21 0.0591 (18) 0.3522 (10) 0.4448 (4) 0.034 (3)* 0.3333

H21 −0.0104 0.3999 0.4321 0.051* 0.3333

C21 0.066 (2) 0.3710 (12) 0.4943 (4) 0.036 (4)* 0.3333

H21A −0.0674 0.3602 0.5077 0.054* 0.3333

H21B 0.1601 0.3201 0.5088 0.054* 0.3333

H21C 0.1100 0.4457 0.5003 0.054* 0.3333

O21′ 0.044 (2) 0.3421 (9) 0.4633 (5) 0.047 (3)* 0.3333

H21′ 0.1510 0.3547 0.4494 0.070* 0.3333

C21′ 0.087 (4) 0.3125 (17) 0.5109 (5) 0.070 (6)* 0.3333

H21D −0.0285 0.2741 0.5242 0.105* 0.3333

H21E 0.2041 0.2648 0.5118 0.105* 0.3333

H21F 0.1135 0.3781 0.5293 0.105* 0.3333

O31 0.488 (3) 0.1606 (14) 0.5506 (7) 0.052 (4)* 0.1666

H31 0.4070 0.1233 0.5658 0.077* 0.1666

C31 0.677 (4) 0.107 (2) 0.5564 (10) 0.052 (4)* 0.1666

H31A 0.7805 0.1475 0.5392 0.077* 0.1666

H31B 0.7121 0.1054 0.5897 0.077* 0.1666

H31C 0.6690 0.0331 0.5443 0.077* 0.1666

O31′ 0.470 (3) 0.2318 (15) 0.5193 (6) 0.052 (4)* 0.1666

H31′ 0.5308 0.2905 0.5213 0.077* 0.1666

(9)

supporting information

sup-6

Acta Cryst. (2002). E58, o1031–o1033

H31D 0.5575 0.0810 0.5047 0.077* 0.1666

H31E 0.6826 0.1726 0.4778 0.077* 0.1666

H31F 0.7213 0.1507 0.5323 0.077* 0.1666

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

N1 0.0346 (19) 0.0194 (16) 0.0222 (17) −0.003 (2) 0.000 (2) −0.0008 (13) C2 0.025 (2) 0.024 (2) 0.029 (2) −0.003 (3) −0.004 (2) 0.0034 (18) O2 0.0476 (19) 0.0268 (15) 0.0267 (15) −0.0099 (19) −0.0022 (18) −0.0095 (13) N3 0.0358 (19) 0.0252 (16) 0.0201 (17) 0.000 (2) 0.001 (2) 0.0018 (13) C4 0.023 (2) 0.029 (2) 0.024 (2) 0.000 (3) 0.005 (2) −0.0015 (17) N4 0.053 (2) 0.0216 (17) 0.0215 (18) −0.004 (2) 0.003 (2) 0.0056 (14) C5 0.027 (2) 0.030 (2) 0.025 (2) 0.000 (3) −0.003 (3) −0.0027 (17) C6 0.027 (2) 0.028 (2) 0.025 (2) 0.002 (3) 0.002 (3) −0.0008 (17) O6 0.050 (2) 0.0250 (16) 0.0267 (15) 0.000 (2) 0.003 (2) −0.0023 (12) O1′ 0.035 (2) 0.041 (2) 0.052 (2) 0.0084 (18) 0.0071 (18) 0.0136 (18) C3′ 0.033 (3) 0.021 (2) 0.027 (2) −0.003 (2) 0.000 (2) −0.006 (2) O3′ 0.0353 (18) 0.0309 (17) 0.0314 (18) 0.0062 (15) −0.0002 (16) 0.0031 (14) C4′ 0.035 (2) 0.032 (2) 0.0185 (19) 0.000 (3) 0.003 (2) 0.0044 (17) C5′ 0.029 (3) 0.046 (3) 0.032 (3) −0.008 (3) 0.000 (2) 0.008 (3) C2′ 0.038 (3) 0.035 (3) 0.028 (2) −0.002 (2) −0.004 (2) 0.017 (2) C6′ 0.036 (4) 0.031 (3) 0.019 (6) 0.004 (3) 0.008 (5) 0.013 (4) O6′ 0.055 (7) 0.023 (4) 0.025 (5) 0.013 (5) 0.006 (5) 0.014 (3) C6′B 0.036 (4) 0.031 (3) 0.019 (6) 0.004 (3) 0.008 (5) 0.013 (4) O6′B 0.045 (6) 0.052 (7) 0.043 (6) −0.004 (5) 0.004 (5) 0.015 (5) C6′C 0.036 (4) 0.031 (3) 0.019 (6) 0.004 (3) 0.008 (5) 0.013 (4) O6′C 0.033 (6) 0.054 (7) 0.031 (6) 0.008 (5) 0.008 (5) −0.011 (5)

Geometric parameters (Å, º)

N1—C2 1.399 (5) O6′—H6′ 0.8400

N1—C6 1.417 (5) C6′B—O6′B 1.399 (11)

N1—C4′ 1.483 (5) C6′B—H6′3 0.9900

C2—O2 1.218 (5) C6′B—H6′4 0.9900

C2—N3 1.354 (5) O6′B—H6′B 0.8400

N3—C4 1.364 (5) C6′C—O6′C 1.397 (10)

N3—H3 0.8800 C6′C—H6′5 0.9900

C4—N4 1.350 (5) C6′C—H6′6 0.9900

C4—C5 1.381 (6) O6′C—H6′C 0.8400

N4—H4B 0.8800 O21—C21 1.45

N4—H4A 0.8800 O21—H21 0.84

C5—C6 1.396 (5) C21—H21A 0.99

C5—H5 0.9500 C21—H21B 0.99

C6—O6 1.248 (5) C21—H21C 0.99

O1′—C2′ 1.423 (6) O21′—C21′ 1.45

O1′—C5′ 1.442 (6) O21′—H21′ 0.84

(10)

C3′—C2′ 1.491 (7) C21′—H21E 0.99

C3′—C4′ 1.557 (7) C21′—H21F 0.99

C3′—H3′1 1.0000 O31—C31 1.45

O3′—H3′ 0.8400 O31—H31 0.84

C4′—C5′ 1.509 (7) C31—H31A 0.99

C4′—H4′1 1.0000 C31—H31B 0.99

C5′—H5′2 0.9900 C31—H31C 0.99

C5′—H5′1 0.9900 O31′—C31′ 1.45

C2′—C6′ 1.547 (9) O31′—H31′ 0.84

C2′—H2′1 0.932 (11) C31′—H31D 0.99

C6′—O6′ 1.405 (10) C31′—H31E 0.99

C6′—H6′1 0.9900 C31′—H31F 0.99

C6′—H6′2 0.9900

C2—N1—C6 122.8 (3) C3′—C2′—H2′1 127 (3)

C2—N1—C4′ 118.1 (3) C6′—C2′—H2′1 101 (3)

C6—N1—C4′ 119.0 (3) O6′—C6′—C2′ 110.5 (9)

O2—C2—N3 122.4 (4) O6′—C6′—H6′1 109.5

O2—C2—N1 122.7 (3) C2′—C6′—H6′1 109.5

N3—C2—N1 114.9 (3) O6′—C6′—H6′2 109.5

C2—N3—C4 125.4 (3) C2′—C6′—H6′2 109.5

C2—N3—H3 117.3 H6′1—C6′—H6′2 108.1

C4—N3—H3 117.3 C6′—O6′—H6′ 109.5

N4—C4—N3 116.6 (3) O6′B—C6′B—H6′3 107.5

N4—C4—C5 123.7 (4) O6′B—C6′B—H6′4 107.5

N3—C4—C5 119.7 (4) H6′3—C6′B—H6′4 107.0

C4—N4—H4B 120.0 C6′B—O6′B—H6′B 109.5

C4—N4—H4A 120.0 O6′C—C6′C—H6′5 110.7

H4B—N4—H4A 120.0 O6′C—C6′C—H6′6 110.7

C4—C5—C6 119.1 (4) H6′5—C6′C—H6′6 108.8

C4—C5—H5 120.4 C6′C—O6′C—H6′C 109.5

C6—C5—H5 120.4 C21—O21—H21 109.5

O6—C6—C5 124.7 (4) O21—C21—H21A 109.5

O6—C6—N1 117.2 (3) O21—C21—H21B 109.5

C5—C6—N1 118.1 (3) O21—C21—H21C 109.5

C2′—O1′—C5′ 106.1 (4) H21A—C21—H21B 109.4

O3′—C3′—C2′ 114.3 (4) H21A—C21—H21C 109.4

O3′—C3′—C4′ 115.3 (4) H21B—C21—H21C 109.4

C2′—C3′—C4′ 100.2 (4) C21′—O21′—H21′ 109.5

O3′—C3′—H3′1 108.9 O21′—C21′—H21D 109.5

C2′—C3′—H3′1 108.9 O21′—C21′—H21E 109.5

C4′—C3′—H3′1 108.9 O21′—C21′—H21F 109.5

C3′—O3′—H3′ 109.5 H21D—C21′—H21E 109.4

N1—C4′—C5′ 115.5 (4) H21D—C21′—H21F 109.4

N1—C4′—C3′ 115.3 (4) H21E—C21′—H21F 109.4

C5′—C4′—C3′ 104.6 (3) C31—O31—H31 105.2

N1—C4′—H4′1 107.0 O31—C31—H31A 109.5

(11)

supporting information

sup-8

Acta Cryst. (2002). E58, o1031–o1033

C3′—C4′—H4′1 107.0 O31—C31—H31C 109.5

O1′—C5′—C4′ 107.3 (4) H31A—C31—H31B 109.4

O1′—C5′—H5′2 110.3 H31A—C31—H31C 109.4

C4′—C5′—H5′2 110.3 H31B—C31—H31C 109.4

O1′—C5′—H5′1 110.2 C31′—O31′—H31′ 105.2

C4′—C5′—H5′1 110.3 O31′—C31′—H31D 109.5

H5′2—C5′—H5′1 108.5 O31′—C31′—H31E 109.5

O1′—C2′—C3′ 106.6 (4) O31′—C31′—H31F 109.5

O1′—C2′—C6′ 103.2 (12) H31D—C31′—H31E 109.4

C3′—C2′—C6′ 113.7 (6) H31D—C31′—H31F 109.4

O1′—C2′—H2′1 102 (3) H31E—C31′—H31F 109.4

C6—N1—C2—O2 179.9 (5) C2—N1—C4′—C3′ 116.8 (5)

C4′—N1—C2—O2 0.4 (9) C6—N1—C4′—C3′ −62.7 (6)

C6—N1—C2—N3 0.0 (8) O3′—C3′—C4′—N1 −84.2 (5)

C4′—N1—C2—N3 −179.4 (4) C2′—C3′—C4′—N1 152.7 (4)

O2—C2—N3—C4 −179.4 (5) O3′—C3′—C4′—C5′ 147.8 (4)

N1—C2—N3—C4 0.5 (8) C2′—C3′—C4′—C5′ 24.7 (4)

C2—N3—C4—N4 178.7 (5) C2′—O1′—C5′—C4′ −20.1 (5)

C2—N3—C4—C5 −1.1 (8) N1—C4′—C5′—O1′ −131.7 (4)

N4—C4—C5—C6 −178.7 (5) C3′—C4′—C5′—O1′ −3.9 (4)

N3—C4—C5—C6 1.1 (8) C5′—O1′—C2′—C3′ 37.8 (5)

C4—C5—C6—O6 179.9 (5) C5′—O1′—C2′—C6′ 157.8 (7)

C4—C5—C6—N1 −0.6 (8) O3′—C3′—C2′—O1′ −162.1 (4)

C2—N1—C6—O6 179.6 (5) C4′—C3′—C2′—O1′ −38.3 (4)

C4′—N1—C6—O6 −1.0 (8) O3′—C3′—C2′—C6′ 84.8 (14)

C2—N1—C6—C5 0.1 (8) C4′—C3′—C2′—C6′ −151.4 (14)

C4′—N1—C6—C5 179.5 (5) O1′—C2′—C6′—O6′ 74 (2)

C2—N1—C4′—C5′ −120.9 (5) C3′—C2′—C6′—O6′ −171.2 (14) C6—N1—C4′—C5′ 59.7 (6)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N3—H3···O6i _0.88 _1.90 _{2.724 (4)} ₁₅₅

N4—H4A···O3′ii _0.88 _2.08 _{2.898 (5)} ₁₅₅

N4—H4B···O6i _0.88 _2.10 _{2.858 (5)} ₁₄₄

O6′—H6′···O31iii _0.84 _2.18 _{2.57 (3)} ₁₀₈

O6′—H6′···O31′iii _0.84 _2.30 _{2.85 (5)} ₁₂₃

O6′B—H6′B···O2iv _0.84 _2.05 _{2.793 (12)} ₁₄₇

O6′C—H6′C···N4v _0.84 _2.35 _{3.041 (10)} ₁₄₀

O6′C—H6′C···O1′ 0.84 2.32 2.786 (12) 115

O3′—H3′···O21vi _0.84 _1.88 _{2.722 (12)} ₁₇₅

O3′—H3′···O21′vi _0.84 _2.11 _{2.936 (13)} ₁₇₀

O3′—H3′···O31vii _0.84 _1.72 _{2.55 (2)} ₁₆₈

O3′—H3′···O31′vii _0.84 _2.07 _{2.75 (15)} ₁₃₇

O21—H21···O1′viii _0.84 _2.02 _{2.856 (13)} ₁₇₃

(12)

O31—H31···O1′ix _0.84 _2.11 _{2.851 (15)} ₁₄₆

O31′—H31′···O6′ 0.84 2.22 2.81 (2) 128

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