Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109029813/gg3204sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109029813/gg3204Isup2.hkl |
CCDC reference: 749706
Compound (Ia) was synthesized as described by Leonard et al. (2009) and crystallized from aqueous methanol (decomposition above 463 K). For the diffraction experiment, a single crystal was mounted on a MiTeGen MicroMounts fibre in a thin smear of oil. [Please check crystal description in CIF: Splitter?]
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 inconclusive values (Flack & Bernardinelli, 2000) [-0.2 (8)]. Therefore, 1339 Friedel equivalents were merged before the final refinement. The known configuration of the parent molecule was used to define the enantiomer employed in the refined model. All H atoms were found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, C- and N-bound H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98 Å and N—H = 0.86 Å; AFIX 93) and constrained to ride on their parent atoms with Uiso(H) values of 1.2Ueq(C,N). The OH groups were refined as rigid groups allowed to rotate but not tip [O—H = 0.82 Å and Uiso(H) = 1.5Ueq(O); AFIX 147]. The H atom of the water molecule was also treated as riding but in this case the Uiso(H) parameter was refined.
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 & Putz, 2004); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
C12H13N5O4·0.5H2O | F(000) = 1256 |
Mr = 300.28 | Dx = 1.495 Mg m−3 |
Orthorhombic, C2221 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: C 2c 2 | Cell parameters from 9979 reflections |
a = 9.5382 (7) Å | θ = 2.9–26.4° |
b = 9.9155 (6) Å | µ = 0.12 mm−1 |
c = 28.2197 (19) Å | T = 296 K |
V = 2668.9 (3) Å3 | Splitter, colourless |
Z = 8 | 0.30 × 0.10 × 0.10 mm |
Bruker APEXII CCD area-detector diffractometer | 1790 independent reflections |
Radiation source: fine-focus sealed tube | 1646 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.039 |
ϕ and ω scans | θmax = 27.9°, θmin = 2.9° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −11→12 |
Tmin = 0.966, Tmax = 0.988 | k = −12→12 |
41187 measured reflections | l = −37→37 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.031 | H-atom parameters constrained |
wR(F2) = 0.075 | w = 1/[σ2(Fo2) + (0.0406P)2 + 1.5275P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max = 0.001 |
1790 reflections | Δρmax = 0.27 e Å−3 |
199 parameters | Δρmin = −0.21 e Å−3 |
0 restraints | Absolute structure: established by known chemical absolute configuration |
Primary atom site location: structure-invariant direct methods |
C12H13N5O4·0.5H2O | V = 2668.9 (3) Å3 |
Mr = 300.28 | Z = 8 |
Orthorhombic, C2221 | Mo Kα radiation |
a = 9.5382 (7) Å | µ = 0.12 mm−1 |
b = 9.9155 (6) Å | T = 296 K |
c = 28.2197 (19) Å | 0.30 × 0.10 × 0.10 mm |
Bruker APEXII CCD area-detector diffractometer | 1790 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 1646 reflections with I > 2σ(I) |
Tmin = 0.966, Tmax = 0.988 | Rint = 0.039 |
41187 measured reflections |
R[F2 > 2σ(F2)] = 0.031 | 0 restraints |
wR(F2) = 0.075 | H-atom parameters constrained |
S = 1.08 | Δρmax = 0.27 e Å−3 |
1790 reflections | Δρmin = −0.21 e Å−3 |
199 parameters | Absolute structure: established by known chemical absolute configuration |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.01584 (17) | 0.65934 (16) | 0.96617 (5) | 0.0155 (3) | |
C2 | −0.0650 (2) | 0.5842 (2) | 0.93975 (6) | 0.0146 (4) | |
H2A | −0.1610 | 0.5988 | 0.9423 | 0.018* | |
N3 | −0.02344 (16) | 0.48767 (16) | 0.90916 (5) | 0.0121 (3) | |
C4 | 0.11907 (19) | 0.46217 (18) | 0.90641 (6) | 0.0125 (4) | |
C5 | 0.21173 (19) | 0.53915 (19) | 0.93384 (6) | 0.0123 (4) | |
C6 | 0.1587 (2) | 0.64278 (19) | 0.96291 (6) | 0.0129 (4) | |
N6 | 0.23575 (17) | 0.72814 (17) | 0.98799 (5) | 0.0164 (4) | |
H6A | 0.1958 | 0.7891 | 1.0049 | 0.020* | |
H6B | 0.3257 | 0.7225 | 0.9873 | 0.020* | |
C7 | 0.34664 (19) | 0.48597 (19) | 0.92184 (6) | 0.0128 (4) | |
C72 | 0.4797 (2) | 0.53111 (19) | 0.93716 (6) | 0.0140 (4) | |
N72 | 0.58793 (18) | 0.57019 (19) | 0.94905 (6) | 0.0209 (4) | |
C8 | 0.3208 (2) | 0.38466 (19) | 0.88905 (6) | 0.0139 (4) | |
H8A | 0.3910 | 0.3327 | 0.8752 | 0.017* | |
N9 | 0.18193 (16) | 0.36925 (16) | 0.87919 (5) | 0.0135 (3) | |
C1' | −0.12782 (19) | 0.42849 (18) | 0.87687 (6) | 0.0129 (4) | |
H1'A | −0.2217 | 0.4571 | 0.8868 | 0.016* | |
C2' | −0.1060 (2) | 0.46642 (18) | 0.82469 (6) | 0.0126 (4) | |
H2'A | −0.0067 | 0.4560 | 0.8166 | 0.015* | |
O2' | −0.14862 (14) | 0.59890 (13) | 0.81417 (5) | 0.0157 (3) | |
H2'B | −0.2341 | 0.6010 | 0.8110 | 0.024* | |
C3' | −0.18995 (19) | 0.35451 (19) | 0.80091 (6) | 0.0146 (4) | |
H3'A | −0.1624 | 0.3404 | 0.7678 | 0.018* | |
O3' | −0.33225 (14) | 0.39620 (14) | 0.80541 (5) | 0.0210 (3) | |
H3' | −0.3820 | 0.3489 | 0.7885 | 0.032* | |
C4' | −0.1574 (2) | 0.23186 (19) | 0.83233 (6) | 0.0134 (4) | |
H4'A | −0.2427 | 0.1775 | 0.8356 | 0.016* | |
O4' | −0.11985 (14) | 0.28641 (13) | 0.87881 (4) | 0.0137 (3) | |
C5' | −0.0396 (2) | 0.14183 (19) | 0.81490 (7) | 0.0145 (4) | |
H5'B | −0.0229 | 0.0718 | 0.8382 | 0.017* | |
H5'C | −0.0690 | 0.0983 | 0.7858 | 0.017* | |
O5' | 0.08807 (13) | 0.21210 (13) | 0.80646 (5) | 0.0144 (3) | |
H5' | 0.1083 | 0.2572 | 0.8298 | 0.022* | |
O10 | −0.5000 | 0.24101 (19) | 0.7500 | 0.0164 (4) | |
H10 | −0.5464 | 0.1944 | 0.7680 | 0.036 (8)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0109 (8) | 0.0193 (8) | 0.0162 (8) | 0.0011 (7) | −0.0012 (6) | −0.0060 (6) |
C2 | 0.0098 (9) | 0.0176 (9) | 0.0165 (9) | 0.0013 (8) | 0.0011 (7) | −0.0040 (7) |
N3 | 0.0072 (7) | 0.0148 (7) | 0.0144 (7) | −0.0010 (6) | −0.0006 (6) | −0.0015 (6) |
C4 | 0.0108 (9) | 0.0128 (9) | 0.0139 (9) | 0.0002 (8) | 0.0007 (7) | 0.0006 (7) |
C5 | 0.0106 (8) | 0.0135 (9) | 0.0127 (9) | 0.0002 (7) | −0.0005 (7) | 0.0022 (7) |
C6 | 0.0123 (9) | 0.0149 (8) | 0.0114 (8) | 0.0017 (8) | −0.0009 (7) | 0.0005 (7) |
N6 | 0.0092 (8) | 0.0196 (9) | 0.0203 (9) | 0.0014 (7) | −0.0013 (6) | −0.0088 (7) |
C7 | 0.0095 (8) | 0.0137 (8) | 0.0152 (8) | 0.0013 (7) | 0.0013 (7) | 0.0006 (7) |
C72 | 0.0122 (9) | 0.0157 (9) | 0.0140 (8) | 0.0036 (8) | 0.0016 (7) | −0.0010 (7) |
N72 | 0.0122 (8) | 0.0279 (10) | 0.0225 (9) | −0.0009 (7) | 0.0001 (7) | −0.0057 (7) |
C8 | 0.0112 (9) | 0.0138 (9) | 0.0166 (9) | 0.0025 (7) | 0.0007 (7) | −0.0004 (7) |
N9 | 0.0095 (8) | 0.0144 (7) | 0.0167 (8) | 0.0004 (6) | 0.0006 (6) | −0.0031 (6) |
C1' | 0.0085 (9) | 0.0131 (8) | 0.0171 (9) | −0.0010 (7) | −0.0014 (7) | −0.0032 (7) |
C2' | 0.0097 (8) | 0.0134 (9) | 0.0146 (8) | 0.0023 (8) | 0.0000 (7) | −0.0012 (7) |
O2' | 0.0100 (6) | 0.0143 (6) | 0.0227 (7) | 0.0023 (5) | −0.0011 (6) | 0.0008 (5) |
C3' | 0.0110 (9) | 0.0165 (9) | 0.0165 (9) | 0.0033 (7) | −0.0021 (7) | −0.0047 (7) |
O3' | 0.0102 (7) | 0.0212 (7) | 0.0316 (8) | 0.0034 (6) | −0.0068 (6) | −0.0124 (6) |
C4' | 0.0103 (9) | 0.0137 (8) | 0.0163 (9) | −0.0023 (8) | 0.0003 (7) | −0.0038 (7) |
O4' | 0.0145 (7) | 0.0118 (6) | 0.0147 (6) | −0.0012 (5) | 0.0004 (5) | −0.0030 (5) |
C5' | 0.0140 (9) | 0.0117 (8) | 0.0179 (9) | −0.0004 (7) | 0.0030 (7) | −0.0032 (7) |
O5' | 0.0112 (6) | 0.0151 (6) | 0.0170 (6) | 0.0000 (5) | 0.0018 (5) | −0.0037 (5) |
O10 | 0.0148 (10) | 0.0156 (9) | 0.0187 (9) | 0.000 | −0.0009 (8) | 0.000 |
N1—C2 | 1.306 (2) | C1'—C2' | 1.534 (2) |
N1—C6 | 1.375 (3) | C1'—H1'A | 0.9800 |
C2—N3 | 1.349 (2) | C2'—O2' | 1.407 (2) |
C2—H2A | 0.9300 | C2'—C3' | 1.524 (3) |
N3—C4 | 1.385 (2) | C2'—H2'A | 0.9800 |
N3—C1' | 1.472 (2) | O2'—H2'B | 0.8200 |
C4—N9 | 1.341 (2) | C3'—O3' | 1.424 (2) |
C4—C5 | 1.401 (3) | C3'—C4' | 1.537 (3) |
C5—C6 | 1.409 (3) | C3'—H3'A | 0.9800 |
C5—C7 | 1.431 (3) | O3'—H3' | 0.8200 |
C6—N6 | 1.326 (2) | C4'—O4' | 1.463 (2) |
N6—H6A | 0.8600 | C4'—C5' | 1.517 (3) |
N6—H6B | 0.8600 | C4'—H4'A | 0.9800 |
C7—C8 | 1.388 (3) | C5'—O5' | 1.423 (2) |
C7—C72 | 1.414 (3) | C5'—H5'B | 0.9700 |
C72—N72 | 1.153 (3) | C5'—H5'C | 0.9700 |
C8—N9 | 1.362 (3) | O5'—H5' | 0.8200 |
C8—H8A | 0.9300 | O10—H10 | 0.8170 |
C1'—O4' | 1.412 (2) | ||
C2—N1—C6 | 118.61 (16) | N3—C1'—H1'A | 109.1 |
N1—C2—N3 | 126.63 (17) | C2'—C1'—H1'A | 109.1 |
N1—C2—H2A | 116.7 | O2'—C2'—C3' | 115.79 (15) |
N3—C2—H2A | 116.7 | O2'—C2'—C1' | 113.10 (15) |
C2—N3—C4 | 117.00 (16) | C3'—C2'—C1' | 99.96 (14) |
C2—N3—C1' | 118.71 (15) | O2'—C2'—H2'A | 109.2 |
C4—N3—C1' | 123.82 (15) | C3'—C2'—H2'A | 109.2 |
N9—C4—N3 | 126.61 (17) | C1'—C2'—H2'A | 109.2 |
N9—C4—C5 | 114.12 (16) | C2'—O2'—H2'B | 109.5 |
N3—C4—C5 | 119.27 (17) | O3'—C3'—C2' | 104.48 (14) |
C4—C5—C6 | 119.51 (17) | O3'—C3'—C4' | 111.76 (16) |
C4—C5—C7 | 103.64 (16) | C2'—C3'—C4' | 102.47 (14) |
C6—C5—C7 | 136.83 (18) | O3'—C3'—H3'A | 112.5 |
N6—C6—N1 | 115.94 (17) | C2'—C3'—H3'A | 112.5 |
N6—C6—C5 | 125.27 (18) | C4'—C3'—H3'A | 112.5 |
N1—C6—C5 | 118.79 (17) | C3'—O3'—H3' | 109.5 |
C6—N6—H6A | 120.0 | O4'—C4'—C5' | 109.09 (15) |
C6—N6—H6B | 120.0 | O4'—C4'—C3' | 105.91 (14) |
H6A—N6—H6B | 120.0 | C5'—C4'—C3' | 115.35 (16) |
C8—C7—C72 | 126.33 (17) | O4'—C4'—H4'A | 108.8 |
C8—C7—C5 | 105.37 (16) | C5'—C4'—H4'A | 108.8 |
C72—C7—C5 | 128.18 (16) | C3'—C4'—H4'A | 108.8 |
N72—C72—C7 | 178.6 (2) | C1'—O4'—C4' | 108.71 (14) |
N9—C8—C7 | 112.94 (17) | O5'—C5'—C4' | 113.57 (15) |
N9—C8—H8A | 123.5 | O5'—C5'—H5'B | 108.9 |
C7—C8—H8A | 123.5 | C4'—C5'—H5'B | 108.9 |
C4—N9—C8 | 103.93 (16) | O5'—C5'—H5'C | 108.9 |
O4'—C1'—N3 | 109.71 (15) | C4'—C5'—H5'C | 108.9 |
O4'—C1'—C2' | 105.94 (14) | H5'B—C5'—H5'C | 107.7 |
N3—C1'—C2' | 113.88 (15) | C5'—O5'—H5' | 109.5 |
O4'—C1'—H1'A | 109.1 | ||
C6—N1—C2—N3 | 1.1 (3) | C5—C4—N9—C8 | 0.3 (2) |
N1—C2—N3—C4 | 2.2 (3) | C7—C8—N9—C4 | −0.2 (2) |
N1—C2—N3—C1' | −170.30 (18) | C2—N3—C1'—O4' | −130.59 (17) |
C2—N3—C4—N9 | 178.61 (17) | C4—N3—C1'—O4' | 57.5 (2) |
C1'—N3—C4—N9 | −9.3 (3) | C2—N3—C1'—C2' | 110.87 (18) |
C2—N3—C4—C5 | −2.0 (3) | C4—N3—C1'—C2' | −61.1 (2) |
C1'—N3—C4—C5 | 170.10 (16) | O4'—C1'—C2'—O2' | 163.43 (15) |
N9—C4—C5—C6 | 178.17 (16) | N3—C1'—C2'—O2' | −75.90 (19) |
N3—C4—C5—C6 | −1.3 (3) | O4'—C1'—C2'—C3' | 39.72 (17) |
N9—C4—C5—C7 | −0.2 (2) | N3—C1'—C2'—C3' | 160.38 (15) |
N3—C4—C5—C7 | −179.71 (17) | O2'—C2'—C3'—O3' | −43.1 (2) |
C2—N1—C6—N6 | 175.38 (16) | C1'—C2'—C3'—O3' | 78.69 (17) |
C2—N1—C6—C5 | −4.5 (3) | O2'—C2'—C3'—C4' | −159.82 (15) |
C4—C5—C6—N6 | −175.27 (17) | C1'—C2'—C3'—C4' | −38.00 (17) |
C7—C5—C6—N6 | 2.4 (3) | O3'—C3'—C4'—O4' | −86.42 (17) |
C4—C5—C6—N1 | 4.6 (3) | C2'—C3'—C4'—O4' | 24.92 (19) |
C7—C5—C6—N1 | −177.7 (2) | O3'—C3'—C4'—C5' | 152.82 (16) |
C4—C5—C7—C8 | 0.05 (19) | C2'—C3'—C4'—C5' | −95.84 (18) |
C6—C5—C7—C8 | −177.9 (2) | N3—C1'—O4'—C4' | −148.44 (14) |
C4—C5—C7—C72 | 176.20 (19) | C2'—C1'—O4'—C4' | −25.10 (19) |
C6—C5—C7—C72 | −1.7 (3) | C5'—C4'—O4'—C1' | 124.70 (16) |
C72—C7—C8—N9 | −176.12 (18) | C3'—C4'—O4'—C1' | 0.0 (2) |
C5—C7—C8—N9 | 0.1 (2) | O4'—C4'—C5'—O5' | −64.63 (19) |
N3—C4—N9—C8 | 179.74 (18) | C3'—C4'—C5'—O5' | 54.4 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O10—H10···O2′i | 0.82 | 1.88 | 2.6971 (17) | 174 |
O5′—H5′···N9 | 0.82 | 1.92 | 2.728 (2) | 171 |
O3′—H3′···O10 | 0.82 | 1.90 | 2.7153 (17) | 179 |
O2′—H2′B···O5′ii | 0.82 | 2.03 | 2.7594 (18) | 148 |
N6—H6B···N1iii | 0.86 | 2.53 | 3.171 (2) | 132 |
N6—H6A···N72iv | 0.86 | 2.17 | 3.024 (2) | 175 |
Symmetry codes: (i) x−1/2, y−1/2, z; (ii) x−1/2, y+1/2, z; (iii) x+1/2, −y+3/2, −z+2; (iv) x−1/2, −y+3/2, −z+2. |
Experimental details
Crystal data | |
Chemical formula | C12H13N5O4·0.5H2O |
Mr | 300.28 |
Crystal system, space group | Orthorhombic, C2221 |
Temperature (K) | 296 |
a, b, c (Å) | 9.5382 (7), 9.9155 (6), 28.2197 (19) |
V (Å3) | 2668.9 (3) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.30 × 0.10 × 0.10 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2008) |
Tmin, Tmax | 0.966, 0.988 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 41187, 1790, 1646 |
Rint | 0.039 |
(sin θ/λ)max (Å−1) | 0.658 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.075, 1.08 |
No. of reflections | 1790 |
No. of parameters | 199 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.27, −0.21 |
Absolute structure | Established by known chemical absolute configuration |
Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXTL (Sheldrick, 2008) and Diamond (Brandenburg & Putz, 2004), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
N1—C2 | 1.306 (2) | C7—C72 | 1.414 (3) |
N3—C4 | 1.385 (2) | C72—N72 | 1.153 (3) |
N3—C1' | 1.472 (2) | C8—N9 | 1.362 (3) |
C4—N9 | 1.341 (2) | ||
C2—N1—C6—N6 | 175.38 (16) | C2—N3—C1'—O4' | −130.59 (17) |
C4—C5—C6—N6 | −175.27 (17) | C4—N3—C1'—O4' | 57.5 (2) |
C6—C5—C7—C72 | −1.7 (3) | C3'—C4'—C5'—O5' | 54.4 (2) |
C72—C7—C8—N9 | −176.12 (18) |
D—H···A | D—H | H···A | D···A | D—H···A |
O10—H10···O2'i | 0.82 | 1.88 | 2.6971 (17) | 174.4 |
O5'—H5'···N9 | 0.82 | 1.92 | 2.728 (2) | 171.0 |
O3'—H3'···O10 | 0.82 | 1.90 | 2.7153 (17) | 178.9 |
O2'—H2'B···O5'ii | 0.82 | 2.03 | 2.7594 (18) | 148.4 |
N6—H6B···N1iii | 0.86 | 2.53 | 3.171 (2) | 132.4 |
N6—H6A···N72iv | 0.86 | 2.17 | 3.024 (2) | 175.4 |
Symmetry codes: (i) x−1/2, y−1/2, z; (ii) x−1/2, y+1/2, z; (iii) x+1/2, −y+3/2, −z+2; (iv) x−1/2, −y+3/2, −z+2. |
Toyocamycin is a naturally occurring 7-deazapurine ribonucleoside produced by Streptomyces toyocaensis or other Streptomyces strains (purine numbering is used throughout this discussion) (Nishimura et al., 1956; Ohkuma, 1961). The chemical synthesis of the antibiotic toyocamycin was described by different laboratories (Tolman et al., 1968, 1969; Sharma et al., 1993; Porcari & Townsend, 1999). Moreover, the crystal structure of toyocamycin was reported by Prusiner & Sundaralingam (1978). Recently, the N-3 regioisomer of toyocamycin was synthesized (Leonard et al., 2009). Generally, purine N-3 nucleosides are relatively labile molecules. They are formed as intermediates during convergent nucleoside synthesis under kinetically controlled conditions and are rearranged to the thermodynamically more stable N-9 isomers (Vorbrüggen et al., 1981). In the case of the toyocamycin analogue (Ia), the glycosylic bond is more stable owing to the electronic properties of the 7-deazapurine moiety, a fact which was already reported for other 7-deazapurine nucleosides (Seela & Peng, 2006).
As relatively few X-ray analyses of N-3 nucleosides are known (Kumar et al., 1988, 1989), a single-crystal X-ray analysis of compound (Ia) was performed. The conformation and hydrogen-bonding pattern in the crystalline state is now studied and compared with the closely related structures of toyocamycin, (IIb) (Prusiner & Sundaralingam, 1978), tubercidin, (IIa) (Stroud, 1973; Abola & Sundaralingam, 1973), and 3-isoadenosine, (III) (Kumar et al., 1988). The three-dimensional structure of (Ia) is shown in Fig. 1 and selected geometric parameters are listed in Table 1.
The title compound can form two main tautomers, namely (Ia) and (Ib) as shown in the scheme. Tautomer (Ia) bears an amine group and no H atom at the pyrrole N atom, while tautomer (Ib) carries a pyrrole H atom and an imine group on the pyrimidine moiety. These tautomers differ in bond length. The tautomeric structure (Ia) with two H atoms at N6 is evidenced by X-ray analysis in the solid state and in solution by 1H NMR spectroscopy. For related compounds, it was observed that the rotation around the H2N—C bond of the amine group is restricted, causing two distinct signals in the 1H NMR spectrum due to the different environments adopted by this group (Seela & Bussmann, 1984). This is also found for compound (Ia). The bond lengths between C6 and N6 of the amine substituent are similar in (Ia) and (IIb). On the other hand, in (Ia), the C2—N1 bond is significantly shorter [1.306 (2) Å] than the C4—N3 bond [1.385 (2) Å], while in toyocamycin these bonds are of almost equal length (C2—N1 = 1.3471 Å and C4—N3 = 1.3470 Å; Prusiner & Sundaralingam, 1978). The same effect was observed in the crystal structure of 3-isoadenosine (Kumar et al., 1988). Altogether, this confirms that tautomeric (Ia) exists in the solid state and in dimethyl sulfoxide solution.
For the common purine nucleosides, the preferred conformation at the N-glycosylic bond is usually anti (Saenger, 1984). The orientation of the nucleobase relative to the sugar moiety (syn/anti) of purine nucleosides is defined by the torsion angle χ(O4'—C1'—N9—C4) (purine numbering; IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). For the N-3 nucleoside (Ia), a different notation has to be used in analogy to the already reported definition for the N-3 nucleoside (III). The torsion angle χ is defined by O4'—C1'—N3—C4 (Kumar et al., 1988).
Contrary to the crystal structure of (III), the glycosylic bond torsion angle of (Ia) is in the syn range, with a χ value of 57.51 (17)°. This conformation differs from that in toyocamycin [N-9 isomer, (IIb)], which adopts an anti conformation at the glycosylic bond (χ = -121.88°; Prusiner & Sundaralingam, 1978). The glycosylic bond conformations of (IIa) and N-3 nucleoside (III) show torsion angle values in the anti range, with χ values of -112.8 (4)° for (IIa) (Abola & Sundaralingam, 1973) and -161.5° for (III) (Kumar et al., 1988). In the tautomeric form (Ib) with an H-atom at the pyrrole N atom, a syn conformation of the glycosylic bond cannot be stabilized by the 5'-OH group acting as H-atom donor. Apparently, this pyrrole N atom is a better H-atom acceptor than that of the imidazole unit in (III). The glycosylic bond length (C1'—N3) of (Ia) is 1.4720 (17) Å. Toyocamycin, C1'-N9 = 1.4490 Å (Prusiner & Sundaralingam, 1978), tubercidin [1.428 (8) Å, Stroud, 1973; 1.438 (4) Å, Abola & Sundaralingam, 1973] and 3-isoadenosine [1.488 (5) Å, Kumar et al., 1988] exhibit longer glycosylic bond lengths.
The most frequently observed sugar ring conformation of purine nucleosides are C2'-endo (`south' or S) and C3'-endo (`north' or N) (Arnott & Hukins, 1972). The sugar moiety of nucleoside (Ia) shows an S conformation with an almost envelope C2'-endo (2E) sugar pucker. The phase angle of pseudorotation (P) and maximum puckering amplitude (τm) (Altona & Sundaralingam, 1972) are 161.6 (2)° and 41.3 (1)°, respectively. In the case of (IIb), the sugar ring conformation is C2'-endo–C3'-exo (2T3,S conformation), with P = 165.7° and τm = 42.5° (Prusiner & Sundaralingam, 1978), and for compound (IIa), C2'-endo–C1'-exo (2T1,S conformation), with P = 149.3° and τm = -43.8° (Abola & Sundaralingam, 1973).
The conformation about the exocyclic C4'—C5' bond, which is defined by the torsion angle γ (O5'—C5'—C4'—C3'), is 54.43 (17)° for (Ia), representing a +sc (gauche, gauche) conformation. This is similar to the parent compound (IIb), which has the torsion angle γ = 57.10° (+sc; gauche, gauche; Prusiner & Sundaralingam, 1978), whereas in compound (IIa), the C4'—C5' bond adopts an ap (gauche, trans) conformation [γ = -178.3 (4)°; Abola & Sundaralingam, 1973].
The 7-deazapurine ring system of (Ia) is nearly planar (for details see the supporting information). The cyano group of (Ia) is slightly inclined by 2.2° with respect to the aromatic ring of the molecule. The amine group is also out of plane; both lie on the same side of the heterocycle [with deviations for C72 of -0.0551 (20) Å, N72 of -0.1360 (24) Å and N6 of -0.1221 (18) Å].
Within the three-dimensional network of (Ia), both the nucleobases and the sugar residues are stacked (Fig. 2). The crystal structure of (Ia) is further stabilized by several intermolecular and one intramolecular hydrogen bonds (O5'—H5'···N9). The intramolecular bond stabilizes the syn conformation of the glycosylic bond. Hydrogen bonds are formed between neighbouring nucleobases with the amine group as H-atom donor (N6—H6A···N72v and N6—H6B···N1iv; see Table 2 for symmetry codes and geometry). The N atom of the cyano group of (Ia) takes part in hydrogen bonding as H-atom acceptor, which is different to the crystal structure of toyocamycin (IIb), in which the cyano group is not involved in any hydrogen bonding (Prusiner & Sundaralingam, 1978). Interbase hydrogen bonding is found in the crystal of (Ia) but not in that of (IIb). Moreover, adjacent sugar residues form hydrogen bonds (O2'—H2'B···O5'iii). The water molecule participates in the hydrogen-bonding pattern as shown in Fig. 3. It acts as a donor (O10—H10···O2'i) as well as an acceptor (O3'—H3'···O10ii) between two nucleoside molecules.
A search for crystallographic nucleoside structures with constrained syn-orientation of the base about the glycosyl bond, caused by an intramolecular hydrogen bond, on the Cambridge Structural Data Base revealed that the large majority of compounds adopts close steric similarities, including the S-conformation of the sugar moiety, the γ+ conformation of the C4'-C5' bond and a syn-conformation with χ = 50–90° (Seela et al., 1998). Although the glycosylation position and the proton acceptor site are different, these properties are also valid for compound (Ia).