Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107027138/sf3039sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270107027138/sf3039Isup2.hkl |
CCDC reference: 665527
Compound (I) was synthesized as described previously (Peng & Seela, 2004) and was crystallized from MeOH (m.p. 470 K). For the diffraction experiment, a single-crystal was fixed at the top of a Lindemann capillary with epoxy resin.
The absolute configuration was obtained from the Flack parameter as well as from the defined configuration of the sugar halide used in the glycosylation reaction.
Atom O5' shows a rather large displacement parameter. This resulted from two different positions (1 and 2) of atom O5'. It is in agreement with the bond lengths and angles. Consequently, two site-occupancy factors, K1 and K2, were introduced, with K2 = 1 - K1.
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 = 0.93–0.98 Å and N—H 0.86 Å (using AFIX 93) and constrained to ride on their parent atoms with Uiso(H)= 1.2Ueq(C)= Ueq(N). The OH groups were refined as rigid groups allowed to rotate but not tip (using AFIX 147) with O—H= 0.82 Å and U(H) = 1.5Ueq(O).
Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS (Siemens, 1996); data reduction: SHELXTL (Sheldrick, 1997); program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1997); software used to prepare material for publication: SHELXTL (Sheldrick, 1997) and PLATON (Spek, 2003).
C11H13BrFN5O3 | F(000) = 728 |
Mr = 362.17 | Dx = 1.807 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 44 reflections |
a = 7.7618 (14) Å | θ = 4.8–13.0° |
b = 9.688 (2) Å | µ = 3.12 mm−1 |
c = 17.707 (3) Å | T = 293 K |
V = 1331.6 (5) Å3 | Block, colourless |
Z = 4 | 0.4 × 0.4 × 0.2 mm |
Bruker P4 diffractometer | 2221 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.027 |
Graphite monochromator | θmax = 30.0°, θmin = 2.3° |
2θ/ω scans | h = −1→10 |
Absorption correction: ψ scan (XSCANS; Siemens, 1996) | k = −13→1 |
Tmin = 0.479, Tmax = 0.791 | l = −24→1 |
2872 measured reflections | 3 standard reflections every 97 reflections |
2687 independent reflections | intensity decay: none |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.040 | w = 1/[σ2(Fo2) + (0.0596P)2 + 0.6193P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.106 | (Δ/σ)max = 0.001 |
S = 1.03 | Δρmax = 0.60 e Å−3 |
2687 reflections | Δρmin = −0.78 e Å−3 |
205 parameters | Extinction correction: SHELXTL (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
1 restraint | Extinction coefficient: 0.0106 (14) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), with 460 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.005 (12) |
C11H13BrFN5O3 | V = 1331.6 (5) Å3 |
Mr = 362.17 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.7618 (14) Å | µ = 3.12 mm−1 |
b = 9.688 (2) Å | T = 293 K |
c = 17.707 (3) Å | 0.4 × 0.4 × 0.2 mm |
Bruker P4 diffractometer | 2221 reflections with I > 2σ(I) |
Absorption correction: ψ scan (XSCANS; Siemens, 1996) | Rint = 0.027 |
Tmin = 0.479, Tmax = 0.791 | 3 standard reflections every 97 reflections |
2872 measured reflections | intensity decay: none |
2687 independent reflections |
R[F2 > 2σ(F2)] = 0.040 | H-atom parameters constrained |
wR(F2) = 0.106 | Δρmax = 0.60 e Å−3 |
S = 1.03 | Δρmin = −0.78 e Å−3 |
2687 reflections | Absolute structure: Flack (1983), with 460 Friedel pairs |
205 parameters | Absolute structure parameter: 0.005 (12) |
1 restraint |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
N1 | 0.1289 (5) | −0.2176 (3) | 1.17059 (18) | 0.0379 (8) | |
C2 | 0.1043 (5) | −0.0791 (4) | 1.1735 (2) | 0.0334 (8) | |
N2 | 0.0856 (5) | −0.0244 (4) | 1.24418 (17) | 0.0448 (9) | |
H2A | 0.0726 | 0.0632 | 1.2497 | 0.054* | |
H2B | 0.0868 | −0.0775 | 1.2831 | 0.054* | |
N3 | 0.1012 (4) | 0.0092 (3) | 1.11538 (16) | 0.0319 (7) | |
C4 | 0.1166 (5) | −0.0545 (4) | 1.0487 (2) | 0.0316 (8) | |
C5 | 0.1358 (6) | −0.1959 (4) | 1.0365 (2) | 0.0352 (8) | |
C6 | 0.1447 (6) | −0.2773 (4) | 1.1025 (2) | 0.0354 (7) | |
N6 | 0.1678 (7) | −0.4144 (4) | 1.0992 (2) | 0.0530 (9) | |
H6A | 0.1721 | −0.4621 | 1.1401 | 0.064* | |
H6B | 0.1782 | −0.4546 | 1.0561 | 0.064* | |
C7 | 0.1390 (6) | −0.2154 (3) | 0.9561 (2) | 0.0367 (8) | |
Br7 | 0.15974 (8) | −0.38288 (4) | 0.90405 (2) | 0.05348 (17) | |
C8 | 0.1262 (7) | −0.0898 (4) | 0.92320 (19) | 0.0429 (10) | |
H8A | 0.1268 | −0.0728 | 0.8715 | 0.051* | |
N9 | 0.1119 (5) | 0.0095 (3) | 0.97942 (17) | 0.0378 (8) | |
C1' | 0.0872 (5) | 0.1555 (4) | 0.9679 (2) | 0.0324 (7) | |
H1' | 0.0840 | 0.2022 | 1.0169 | 0.039* | |
C2' | 0.2240 (5) | 0.2235 (4) | 0.9181 (2) | 0.0347 (8) | |
H2' | 0.2502 | 0.3158 | 0.9376 | 0.042* | |
F2' | 0.3740 (3) | 0.1461 (3) | 0.91499 (15) | 0.0506 (6) | |
C3' | 0.1399 (5) | 0.2360 (3) | 0.84091 (18) | 0.0317 (7) | |
H3' | 0.1510 | 0.1486 | 0.8135 | 0.038* | |
O3' | 0.2044 (4) | 0.3456 (3) | 0.79619 (16) | 0.0439 (7) | |
H3'A | 0.2528 | 0.3140 | 0.7588 | 0.066* | |
C4' | −0.0478 (5) | 0.2595 (4) | 0.86277 (18) | 0.0291 (7) | |
H4' | −0.0654 | 0.3571 | 0.8750 | 0.035* | |
O4' | −0.0725 (4) | 0.1771 (3) | 0.92965 (14) | 0.0385 (6) | |
C5'1 | −0.1749 (7) | 0.2161 (4) | 0.8035 (2) | 0.0404 (9) | 0.690 (7) |
H511 | −0.1646 | 0.2776 | 0.7605 | 0.049* | 0.690 (7) |
H512 | −0.1458 | 0.1238 | 0.7865 | 0.049* | 0.690 (7) |
O5'1 | −0.3436 (6) | 0.2167 (4) | 0.8280 (2) | 0.0407 (11) | 0.690 (7) |
H5'1 | −0.3642 | 0.2900 | 0.8494 | 0.061* | 0.690 (7) |
C5'2 | −0.1749 (7) | 0.2161 (4) | 0.8035 (2) | 0.0404 (9) | 0.310 (7) |
H521 | −0.2910 | 0.2360 | 0.8206 | 0.049* | 0.310 (7) |
H522 | −0.1545 | 0.2678 | 0.7574 | 0.049* | 0.310 (7) |
O5'2 | −0.159 (2) | 0.0754 (9) | 0.7891 (5) | 0.050 (3) | 0.310 (7) |
H5'2 | −0.1662 | 0.0616 | 0.7435 | 0.076* | 0.310 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.047 (2) | 0.0335 (15) | 0.0333 (15) | 0.0020 (16) | 0.0008 (14) | 0.0056 (12) |
C2 | 0.033 (2) | 0.0385 (19) | 0.0291 (16) | −0.0005 (15) | 0.0000 (14) | 0.0029 (14) |
N2 | 0.063 (2) | 0.0452 (18) | 0.0265 (14) | 0.0091 (19) | 0.0050 (15) | 0.0039 (14) |
N3 | 0.0395 (17) | 0.0294 (14) | 0.0269 (13) | 0.0005 (13) | 0.0007 (11) | 0.0006 (11) |
C4 | 0.044 (2) | 0.0271 (15) | 0.0239 (14) | −0.0009 (15) | −0.0008 (14) | 0.0030 (13) |
C5 | 0.045 (2) | 0.0298 (15) | 0.0308 (16) | 0.0003 (17) | −0.0024 (16) | 0.0007 (13) |
C6 | 0.0367 (18) | 0.0302 (16) | 0.0393 (17) | 0.0005 (17) | −0.0031 (19) | 0.0043 (15) |
N6 | 0.081 (3) | 0.0315 (14) | 0.0459 (17) | 0.008 (2) | 0.003 (2) | 0.0057 (15) |
C7 | 0.052 (2) | 0.0264 (15) | 0.0315 (16) | −0.0015 (17) | −0.0028 (18) | −0.0049 (13) |
Br7 | 0.0885 (4) | 0.02863 (18) | 0.0433 (2) | 0.0020 (2) | −0.0004 (2) | −0.00803 (16) |
C8 | 0.074 (3) | 0.0301 (16) | 0.0242 (15) | 0.0019 (19) | −0.0020 (17) | −0.0027 (13) |
N9 | 0.065 (2) | 0.0241 (13) | 0.0246 (13) | 0.0026 (15) | −0.0012 (14) | 0.0003 (11) |
C1' | 0.0441 (19) | 0.0263 (15) | 0.0267 (15) | 0.0019 (15) | −0.0049 (15) | −0.0020 (12) |
C2' | 0.0403 (18) | 0.0264 (16) | 0.0374 (19) | 0.0023 (15) | −0.0028 (15) | −0.0031 (14) |
F2' | 0.0401 (12) | 0.0477 (13) | 0.0639 (16) | 0.0064 (11) | −0.0081 (12) | −0.0014 (12) |
C3' | 0.0446 (19) | 0.0226 (14) | 0.0279 (14) | −0.0024 (17) | 0.0043 (15) | 0.0000 (12) |
O3' | 0.0610 (19) | 0.0328 (13) | 0.0380 (14) | −0.0096 (14) | 0.0163 (13) | 0.0044 (11) |
C4' | 0.0405 (18) | 0.0220 (14) | 0.0249 (14) | 0.0013 (15) | 0.0012 (14) | 0.0014 (12) |
O4' | 0.0407 (13) | 0.0480 (15) | 0.0266 (11) | 0.0003 (14) | 0.0015 (11) | 0.0094 (12) |
C5'1 | 0.053 (2) | 0.0388 (19) | 0.0294 (16) | −0.003 (2) | −0.0036 (19) | 0.0005 (14) |
O5'1 | 0.036 (2) | 0.040 (2) | 0.046 (2) | −0.007 (2) | −0.003 (2) | −0.0023 (17) |
C5'2 | 0.053 (2) | 0.0388 (19) | 0.0294 (16) | −0.003 (2) | −0.0036 (19) | 0.0005 (14) |
O5'2 | 0.087 (8) | 0.034 (4) | 0.030 (4) | −0.020 (6) | −0.003 (5) | −0.004 (3) |
N1—C6 | 1.343 (5) | C1'—O4' | 1.428 (5) |
N1—C2 | 1.356 (5) | C1'—C2' | 1.530 (5) |
C2—N3 | 1.340 (5) | C1'—H1' | 0.9800 |
C2—N2 | 1.366 (5) | C2'—F2' | 1.386 (4) |
N2—H2A | 0.8600 | C2'—C3' | 1.519 (5) |
N2—H2B | 0.8600 | C2'—H2' | 0.9800 |
N3—C4 | 1.337 (5) | C3'—O3' | 1.416 (4) |
C4—N9 | 1.375 (5) | C3'—C4' | 1.524 (5) |
C4—C5 | 1.395 (5) | C3'—H3' | 0.9800 |
C5—C6 | 1.411 (5) | O3'—H3'A | 0.8200 |
C5—C7 | 1.436 (5) | C4'—O4' | 1.441 (4) |
C6—N6 | 1.342 (5) | C4'—C5'1 | 1.500 (5) |
N6—H6A | 0.8600 | C4'—H4' | 0.9800 |
N6—H6B | 0.8600 | C5'1—O5'1 | 1.380 (7) |
C7—C8 | 1.353 (5) | C5'1—H511 | 0.9700 |
C7—Br7 | 1.873 (3) | C5'1—H512 | 0.9700 |
C8—N9 | 1.389 (4) | O5'1—H5'1 | 0.8200 |
C8—H8A | 0.9300 | O5'2—H5'2 | 0.8200 |
N9—C1' | 1.442 (5) | ||
C6—N1—C2 | 118.3 (3) | N9—C1'—C2' | 114.4 (3) |
N3—C2—N1 | 127.2 (4) | O4'—C1'—H1' | 109.3 |
N3—C2—N2 | 117.0 (3) | N9—C1'—H1' | 109.3 |
N1—C2—N2 | 115.7 (3) | C2'—C1'—H1' | 109.3 |
C2—N2—H2A | 120.0 | F2'—C2'—C3' | 111.7 (3) |
C2—N2—H2B | 120.0 | F2'—C2'—C1' | 111.9 (3) |
H2A—N2—H2B | 120.0 | C3'—C2'—C1' | 104.7 (3) |
C4—N3—C2 | 112.4 (3) | F2'—C2'—H2' | 109.5 |
N3—C4—N9 | 125.2 (3) | C3'—C2'—H2' | 109.5 |
N3—C4—C5 | 126.8 (3) | C1'—C2'—H2' | 109.5 |
N9—C4—C5 | 107.9 (3) | O3'—C3'—C2' | 114.2 (3) |
C4—C5—C6 | 115.2 (3) | O3'—C3'—C4' | 111.6 (3) |
C4—C5—C7 | 106.5 (3) | C2'—C3'—C4' | 101.2 (3) |
C6—C5—C7 | 138.3 (4) | O3'—C3'—H3' | 109.8 |
N6—C6—N1 | 118.6 (4) | C2'—C3'—H3' | 109.8 |
N6—C6—C5 | 121.6 (4) | C4'—C3'—H3' | 109.8 |
N1—C6—C5 | 119.9 (3) | C3'—O3'—H3'A | 109.5 |
C6—N6—H6A | 120.0 | O4'—C4'—C5'1 | 109.4 (3) |
C6—N6—H6B | 120.0 | O4'—C4'—C3' | 104.7 (3) |
H6A—N6—H6B | 120.0 | C5'1—C4'—C3' | 114.1 (3) |
C8—C7—C5 | 107.9 (3) | O4'—C4'—H4' | 109.5 |
C8—C7—Br7 | 125.0 (3) | C5'1—C4'—H4' | 109.5 |
C5—C7—Br7 | 127.1 (3) | C3'—C4'—H4' | 109.5 |
C7—C8—N9 | 108.7 (3) | C1'—O4'—C4' | 110.8 (3) |
C7—C8—H8A | 125.7 | O5'1—C5'1—C4' | 113.8 (3) |
N9—C8—H8A | 125.7 | O5'1—C5'1—H511 | 108.8 |
C4—N9—C8 | 109.0 (3) | C4'—C5'1—H511 | 108.8 |
C4—N9—C1' | 124.9 (3) | O5'1—C5'1—H512 | 108.8 |
C8—N9—C1' | 126.0 (3) | C4'—C5'1—H512 | 108.8 |
O4'—C1'—N9 | 109.1 (3) | H511—C5'1—H512 | 107.7 |
O4'—C1'—C2' | 105.4 (3) | ||
C6—N1—C2—N3 | −3.3 (7) | C7—C8—N9—C4 | 0.3 (5) |
C6—N1—C2—N2 | 178.8 (4) | C7—C8—N9—C1' | −176.8 (4) |
N1—C2—N3—C4 | 3.4 (6) | C4—N9—C1'—O4' | −114.8 (4) |
N2—C2—N3—C4 | −178.6 (4) | C8—N9—C1'—O4' | 61.8 (5) |
C2—N3—C4—N9 | 177.7 (4) | C4—N9—C1'—C2' | 127.5 (4) |
C2—N3—C4—C5 | −0.6 (6) | C8—N9—C1'—C2' | −55.9 (6) |
N3—C4—C5—C6 | −2.0 (7) | O4'—C1'—C2'—F2' | −140.6 (3) |
N9—C4—C5—C6 | 179.4 (4) | N9—C1'—C2'—F2' | −20.8 (4) |
N3—C4—C5—C7 | 177.4 (4) | O4'—C1'—C2'—C3' | −19.5 (3) |
N9—C4—C5—C7 | −1.2 (6) | N9—C1'—C2'—C3' | 100.3 (3) |
C2—N1—C6—N6 | −179.5 (5) | F2'—C2'—C3'—O3' | −85.6 (4) |
C2—N1—C6—C5 | 0.1 (6) | C1'—C2'—C3'—O3' | 153.1 (3) |
C4—C5—C6—N6 | −178.2 (5) | F2'—C2'—C3'—C4' | 154.3 (3) |
C7—C5—C6—N6 | 2.6 (10) | C1'—C2'—C3'—C4' | 33.1 (3) |
C4—C5—C6—N1 | 2.3 (6) | O3'—C3'—C4'—O4' | −157.1 (3) |
C7—C5—C6—N1 | −177.0 (6) | C2'—C3'—C4'—O4' | −35.2 (3) |
C4—C5—C7—C8 | 1.3 (6) | O3'—C3'—C4'—C5'1 | 83.3 (4) |
C6—C5—C7—C8 | −179.4 (6) | C2'—C3'—C4'—C5'1 | −154.8 (3) |
C4—C5—C7—Br7 | −179.3 (3) | N9—C1'—O4'—C4' | −126.6 (3) |
C6—C5—C7—Br7 | 0.0 (10) | C2'—C1'—O4'—C4' | −3.3 (4) |
C5—C7—C8—N9 | −1.0 (6) | C5'1—C4'—O4'—C1' | 147.5 (3) |
Br7—C7—C8—N9 | 179.6 (3) | C3'—C4'—O4'—C1' | 24.8 (3) |
N3—C4—N9—C8 | −178.0 (4) | O4'—C4'—C5'1—O5'1 | 53.2 (5) |
C5—C4—N9—C8 | 0.6 (5) | C3'—C4'—C5'1—O5'1 | 170.1 (3) |
N3—C4—N9—C1' | −0.9 (7) | C3'—C4'—C5'1—O5'2 | 60.7 (7) |
C5—C4—N9—C1' | 177.7 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2A···O5′1i | 0.86 | 2.62 | 3.290 (6) | 136 |
N2—H2B···O5′1ii | 0.86 | 2.45 | 3.034 (6) | 126 |
N6—H6A···O5′2iii | 0.86 | 2.12 | 2.857 (10) | 143 |
N6—H6B···Br7 | 0.86 | 2.78 | 3.469 (4) | 138 |
O3′—H3′A···N1iv | 0.82 | 2.04 | 2.857 (4) | 175 |
O5′1—H5′1···N3v | 0.82 | 2.06 | 2.871 (5) | 169 |
O5′2—H5′2···O3′vi | 0.82 | 2.23 | 2.714 (9) | 118 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+2; (ii) −x−1/2, −y, z+1/2; (iii) x+1/2, −y−1/2, −z+2; (iv) −x+1/2, −y, z−1/2; (v) x−1/2, −y+1/2, −z+2; (vi) −x, y−1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C11H13BrFN5O3 |
Mr | 362.17 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 7.7618 (14), 9.688 (2), 17.707 (3) |
V (Å3) | 1331.6 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 3.12 |
Crystal size (mm) | 0.4 × 0.4 × 0.2 |
Data collection | |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | ψ scan (XSCANS; Siemens, 1996) |
Tmin, Tmax | 0.479, 0.791 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2872, 2687, 2221 |
Rint | 0.027 |
(sin θ/λ)max (Å−1) | 0.703 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.040, 0.106, 1.03 |
No. of reflections | 2687 |
No. of parameters | 205 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.60, −0.78 |
Absolute structure | Flack (1983), with 460 Friedel pairs |
Absolute structure parameter | 0.005 (12) |
Computer programs: XSCANS (Siemens, 1996), SHELXTL (Sheldrick, 1997) and PLATON (Spek, 2003).
C2—N2 | 1.366 (5) | N9—C1' | 1.442 (5) |
C6—N6 | 1.342 (5) | C2'—F2' | 1.386 (4) |
C7—Br7 | 1.873 (3) | C5'1—O5'1 | 1.380 (7) |
N1—C2—N2 | 115.7 (3) | N9—C1'—C2' | 114.4 (3) |
N6—C6—N1 | 118.6 (4) | F2'—C2'—C3' | 111.7 (3) |
C8—C7—Br7 | 125.0 (3) | F2'—C2'—C1' | 111.9 (3) |
C5—C7—Br7 | 127.1 (3) | O4'—C4'—C5'1 | 109.4 (3) |
C4—N9—C1' | 124.9 (3) | O5'1—C5'1—C4' | 113.8 (3) |
O4'—C1'—N9 | 109.1 (3) | ||
C6—N1—C2—N3 | −3.3 (7) | C1'—C2'—C3'—C4' | 33.1 (3) |
C7—C5—C6—N6 | 2.6 (10) | C2'—C3'—C4'—O4' | −35.2 (3) |
C6—C5—C7—Br7 | 0.0 (10) | C2'—C3'—C4'—C5'1 | −154.8 (3) |
C4—N9—C1'—O4' | −114.8 (4) | N9—C1'—O4'—C4' | −126.6 (3) |
C8—N9—C1'—O4' | 61.8 (5) | C2'—C1'—O4'—C4' | −3.3 (4) |
O4'—C1'—C2'—F2' | −140.6 (3) | C5'1—C4'—O4'—C1' | 147.5 (3) |
N9—C1'—C2'—F2' | −20.8 (4) | C3'—C4'—O4'—C1' | 24.8 (3) |
O4'—C1'—C2'—C3' | −19.5 (3) | O4'—C4'—C5'1—O5'1 | 53.2 (5) |
N9—C1'—C2'—C3' | 100.3 (3) | C3'—C4'—C5'1—O5'1 | 170.1 (3) |
F2'—C2'—C3'—O3' | −85.6 (4) | C3'—C4'—C5'1—O5'2 | 60.7 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2A···O5'1i | 0.86 | 2.62 | 3.290 (6) | 135.6 |
N2—H2B···O5'1ii | 0.86 | 2.45 | 3.034 (6) | 125.5 |
N6—H6A···O5'2iii | 0.86 | 2.12 | 2.857 (10) | 143.1 |
N6—H6B···Br7 | 0.86 | 2.78 | 3.469 (4) | 137.7 |
O3'—H3'A···N1iv | 0.82 | 2.04 | 2.857 (4) | 174.6 |
O5'1—H5'1···N3v | 0.82 | 2.06 | 2.871 (5) | 169.3 |
O5'2—H5'2···O3'vi | 0.82 | 2.23 | 2.714 (9) | 118.3 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+2; (ii) −x−1/2, −y, z+1/2; (iii) x+1/2, −y−1/2, −z+2; (iv) −x+1/2, −y, z−1/2; (v) x−1/2, −y+1/2, −z+2; (vi) −x, y−1/2, −z+3/2. |
The introduction of halogens in components of nucleic acids generally leads to changes in their physical properties and biological activity. Among the various positions, the 7-position of the 7-deazapurine moiety (purine numbering is used throughout) and the 2'-position of the sugar residue are important modification sites (Seela, Chittepu et al., 2005). A series of 7-substituted 7-deazapurine ribonucleosides and 2'-deoxyribonucleosides exhibit antiviral activity against various RNA and DNA viruses, including Herpes simplex virus types 1 and type 2 (HSV-1 and HSV-2) (Bergstrom et al., 1984; De Clercq et al., 1986). The introduction of the 7-bromo substituent increases the polarizability of the nucleobase and enhances base-stacking interactions, thereby stabilizing the DNA duplex structure (Ramzaeva & Seela, 1996; Seela & Thomas, 1995). The 7-bromo substituent decreases the basicity of the title compound, (I) (pKa = 4.77), compared to the non-halogenated compound (pKa = 5.67), as indicated by the lower pKa value. The nuleobase plays an important role in directing the conformation of the sugar moiety.
The introduction of an F atom instead of H into the 2'-position of the sugar moiety of nucleosides enhances the chemical stability and biological activity of nucleosides (Filler & Naqvi, 1979; Marquez et al., 1990; Masood et al., 1990). It leads to a minor change in the size of the molecule but strongly influences the S/N-conformational equilibrium of the pentofuranose ring in solution (He et al., 2003). In order to elucidate the combined influence of bromination at position 7 of 2-amino-2'-deoxytubercidin and the introduction of a 2'-fluoro substituent in the sugar residue, we have synthesized the title compound 2-amino-7-deaza-7-bromo-2'-deoxy-2'-fluoroadenosine, (I), and subjected it to single-crystal X-ray analysis. The synthesis of the title compound was reported previously (Peng & Seela, 2004). The structure of compound (I) is shown in Fig. 1 and selected geometric parameters are summarized in Table 1.
The orientation of the base relative to the sugar moiety (syn/anti) is denoted by the torsion angle χ, which is defined as O4'-C1'-N9—C4 for purine nucleosides (IUPAC-IUB Joint Commission on Biochemical Nomenclature, 1983). The crystal structure of compound (I) exhibits a torsion angle χ of −114.8 (4)°, falling into the anti range. This value is close to those of compound (IIa) (see scheme) [χ = −105.0 (6)°; Seela, Sirivolu et al., 2005] and (III) (see scheme) [χ = −102.5 (6)°; Seela et al., 2006]. The length of the N-glycosylic bond of nucleoside (I) is 1.442 (5) Å, which is similar to compound (IIa) [1.447 (5) Å; Seela, Sirivolu et al., 2005] and (III) [1.464 (6) Å; Seela et al., 2006]. For the sugar moiety, two major twisted conformations are found, denoted north and south. The north (N) conformation refers to the C3'-endo-C2'-exo conformer, whereas the south (S) conformation represents the C2'-endo-C3'-exo conformer [Seela et al., 2000]. The sugar moiety of compound (I) shows an N conformation with a phase angle of pseudorotation P = 23.3 (4)° and the maximum amplitude of puckering τm = 36.5 (2)° (Altona & Sundaralingam, 1972), indicating that the sugar ring adopts an unsymmetrical twist (C3'-endo-C4'-exo; 3T4). Nucleoside (III) shows the same sugar moiety structure as (I) (P = 19.6° and τm = 32.9°; Seela et al., 2006), whereas compound (IIa) exhibits differences in the N conformation [C3'-endo-C2'-exo, between 3T2 and E3, with P = 5.8 (5)° and τm = 30.0 (3)°; Seela, Sirivolu et al., 2005].
In the crystal of (I), two conformations of the exocyclic C4'-C5' bond were found corresponding to occupancies of 0.69 of conformer 1 (Fig. 1a) and 0.31 of conformer 2 (Fig. 1b). The torsion angle γ is defined as O5'1-C5'1-C4'-C3' for conformer 1 and O5'2-C5'2-C4'-C3' for conformer 2. For conformer 1, this torsion angle is 170.1 (3)°, falling into +ap (trans) range. This is close to compounds (IIa) [γ = 172.0 (4)°; Seela, Sirivolu et al.,2005] and (III) [γ = 171.5 (4)°; Seela et al., 2006]. In contrast, the conformer 2 adopts a conformation with γ = 60.7 (7)° representing a +synclinal (gauche) conformation. The base unit of (I) is essentially planar, with an r.m.s. deviation of 0.0201 Å and a maximum deviation of −0.0369 (3) Å for the ring atom C2. The bromo substituent is located −0.0764 (5) Å below the 7-deazapurine plane on the same side as the 2-amino group [−0.0851 (6) Å] whereas the 6-amino group lies 0.0533 (7) Å above the plane.
In contrast to the behavior in solid state, the spatial conformation of the sugar moiety dynamically interconverts between north (N) and south (S) in solution. This ratio was determined from the vicinal 3J (H, H) coupling constants of the 1H NMR spectrum measured in D2O, using the PSEUROT program (van Wijk & Altona, 1993). The population in an aqueous solution of compound (I) is 0.63 S and 0.37 N, whereas for the non-fluorinated nucleoside, (IIc), the populations are shifted towards S (0.71 S and 0.29 N; Peng & Seela, 2004). This shows that the introduction of an F atom in the arabino position of the sugar moiety enhances the population of the N-conformers. In contrast, the related 8-aza compound, (IIb), incorporating an N atom instead of a C atom at position 8, exclusively forms the N conformation (He et al., 2003).
Compound (I) forms a compact three-dimensional network, which is stabilized by hydrogen bonds and stacking interactions (Fig. 2 and Table 2). The nucleobases are arranged head-to-tail. The two conformers 1 and 2, are linked through hydrogen bonds between neighbouring nucleobases and sugar residues. The N2 and N6 amino groups function as H-atom donors and atoms O5' of both conformers act as H-atom acceptors (N2—H2A···O5'1; N2—H2B···O5'1; N6—H6A···O5'2). Further hydrogen bonds connect neighbouring sugar residues and the exocyclic substituents of the nucleobase. Hydrogen bonds are formed between N3 and H5' of conformer 1 (O5'1-H5'1···N3), while atom H5' of conformer 2 forms a hydrogen bond with O3' (O5'2-H5'2···O3'). Both conformers form two further intermolecular hydrogen bonds (O3'-H3A···N1 and N6—H6B···Br7).