Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803012352/cf6257sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536803012352/cf6257Isup2.hkl |
CCDC reference: 217620
Sulfoxide (II) (0.5 mmol), 2,6-di-tert-butyl-4-methyl pyridine (2.5 mmol), and 4 Å molecular sieves (0.1 g) were dried for 3 h under vacuum in the presence of P2O5. To this mixture was added CH2Cl2 (10 ml) and the reaction mixture was cooled to 195 K. Triflic anhydride (0.6 mmol) was added and the mixture was stirred for 10 min before a solution of the persilylated nucleoside [(III), 0.6 mmol; Nishimura & Iwai, 1964] in CH2Cl2 (1.0 ml) was added dropwise by syringe over 2 min. After 15 min, the reaction mixture turned dark brown–green and a saturated aqueous solution of NaHCO3 was added, before the solution was allowed to warm to room temperature. The resulting solution was filtered through Celite, dried, filtered, and concentrated, to yield a crude oil that was purified by chromatography (2:1, hexanes/EtOAc), yielding (I) (0.35 mmol, 70%) as an oil. The product was recrystallized from 10:1 dichloromethane–hexane (m.p.: 366–367 K).
All H atoms were refined using a riding model, with bond lengths of 0.86 (N—-H), 0.93 (aryl H), 0.97 (CH2), and 0.98 Å (epoxide ring H). For all H atoms, Uiso(H) = 1.2Ueq(parent). Friedel pair reflections were merged prior to final refinement, as the refined Flack (1983) parameter was meaningless.
Data collection: XSCANS (Bruker, 1996); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Bruker, 2001); software used to prepare material for publication: SHELXL97.
C16H13FN2O6 | F(000) = 360 |
Mr = 348.28 | Dx = 1.506 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 96 reflections |
a = 7.3537 (8) Å | θ = 2.8–25.3° |
b = 5.5149 (8) Å | µ = 0.12 mm−1 |
c = 19.290 (2) Å | T = 298 K |
β = 100.928 (9)° | Plate, colorless |
V = 768.13 (17) Å3 | 0.32 × 0.20 × 0.07 mm |
Z = 2 |
Bruker P4 diffractometer | 980 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.048 |
Graphite monochromator | θmax = 27.5°, θmin = 2.8° |
θ/2θ scans | h = −9→9 |
Absorption correction: ψ scan (XPREP; Bruker, 2001) | k = −7→7 |
Tmin = 0.834, Tmax = 0.981 | l = −25→25 |
3910 measured reflections | 3 standard reflections every 97 reflections |
1839 independent reflections | intensity decay: none |
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)] = 0.052 | H-atom parameters constrained |
wR(F2) = 0.151 | w = 1/[σ2(Fo2) + (0.0707P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max < 0.001 |
1839 reflections | Δρmax = 0.27 e Å−3 |
227 parameters | Δρmin = −0.27 e Å−3 |
1 restraint | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.039 (8) |
C16H13FN2O6 | V = 768.13 (17) Å3 |
Mr = 348.28 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 7.3537 (8) Å | µ = 0.12 mm−1 |
b = 5.5149 (8) Å | T = 298 K |
c = 19.290 (2) Å | 0.32 × 0.20 × 0.07 mm |
β = 100.928 (9)° |
Bruker P4 diffractometer | 980 reflections with I > 2σ(I) |
Absorption correction: ψ scan (XPREP; Bruker, 2001) | Rint = 0.048 |
Tmin = 0.834, Tmax = 0.981 | 3 standard reflections every 97 reflections |
3910 measured reflections | intensity decay: none |
1839 independent reflections |
R[F2 > 2σ(F2)] = 0.052 | 1 restraint |
wR(F2) = 0.151 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.27 e Å−3 |
1839 reflections | Δρmin = −0.27 e Å−3 |
227 parameters |
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 | ||
F1 | 0.8732 (4) | −0.4285 (7) | 0.19297 (15) | 0.0615 (9) | |
O1 | 0.5109 (4) | 0.3444 (7) | 0.18779 (16) | 0.0470 (9) | |
O2 | 0.2866 (5) | −0.0274 (7) | 0.1889 (2) | 0.0594 (11) | |
O3 | 0.5312 (6) | 0.5828 (10) | 0.3127 (2) | 0.0737 (13) | |
O4 | 0.4104 (8) | 0.6893 (13) | 0.4046 (3) | 0.123 (2) | |
O5 | 1.0030 (5) | −0.3851 (8) | 0.06968 (17) | 0.0545 (10) | |
O6 | 0.6325 (5) | 0.2691 (8) | 0.00678 (18) | 0.0598 (11) | |
N1 | 0.6133 (5) | 0.0793 (8) | 0.11036 (18) | 0.0387 (9) | |
N2 | 0.8221 (5) | −0.0490 (8) | 0.0413 (2) | 0.0451 (11) | |
H2 | 0.8733 | −0.0263 | 0.0053 | 0.054* | |
C1 | 0.4609 (6) | 0.2329 (10) | 0.1215 (2) | 0.0415 (11) | |
H1 | 0.4393 | 0.3581 | 0.0848 | 0.050* | |
C2 | 0.2817 (6) | 0.1024 (11) | 0.1230 (3) | 0.0514 (13) | |
H2A | 0.1991 | 0.0519 | 0.0794 | 0.062* | |
C3 | 0.2094 (7) | 0.2134 (10) | 0.1808 (3) | 0.0494 (13) | |
H3 | 0.0759 | 0.2381 | 0.1769 | 0.059* | |
C4 | 0.3443 (7) | 0.4048 (10) | 0.2140 (3) | 0.0482 (13) | |
H4 | 0.2998 | 0.5653 | 0.1967 | 0.058* | |
C5 | 0.3866 (8) | 0.4056 (13) | 0.2916 (3) | 0.0682 (17) | |
H5A | 0.2773 | 0.4485 | 0.3102 | 0.082* | |
H5B | 0.4281 | 0.2464 | 0.3092 | 0.082* | |
C6 | 0.5287 (10) | 0.7106 (14) | 0.3701 (3) | 0.0715 (18) | |
C7 | 0.6879 (10) | 0.8800 (13) | 0.3863 (3) | 0.0686 (17) | |
C8 | 0.6836 (12) | 1.0581 (15) | 0.4361 (3) | 0.089 (2) | |
H8 | 0.5856 | 1.0650 | 0.4602 | 0.107* | |
C9 | 0.8265 (16) | 1.2282 (19) | 0.4504 (5) | 0.114 (3) | |
H9 | 0.8222 | 1.3514 | 0.4829 | 0.136* | |
C10 | 0.9705 (15) | 1.213 (2) | 0.4168 (5) | 0.117 (3) | |
H10 | 1.0666 | 1.3244 | 0.4270 | 0.140* | |
C11 | 0.9779 (11) | 1.0343 (17) | 0.3675 (4) | 0.099 (3) | |
H11 | 1.0781 | 1.0268 | 0.3445 | 0.118* | |
C12 | 0.8366 (10) | 0.8664 (15) | 0.3522 (3) | 0.0764 (19) | |
H12 | 0.8415 | 0.7450 | 0.3191 | 0.092* | |
C13 | 0.6756 (6) | −0.1014 (10) | 0.1576 (2) | 0.0416 (11) | |
H13 | 0.6256 | −0.1180 | 0.1982 | 0.050* | |
C14 | 0.8082 (6) | −0.2546 (10) | 0.1459 (2) | 0.0413 (11) | |
C15 | 0.8867 (6) | −0.2409 (10) | 0.0842 (2) | 0.0411 (11) | |
C16 | 0.6836 (6) | 0.1120 (10) | 0.0497 (2) | 0.0412 (11) |
U11 | U22 | U33 | U12 | U13 | U23 | |
F1 | 0.0523 (18) | 0.065 (2) | 0.0735 (19) | 0.0231 (18) | 0.0278 (14) | 0.0224 (19) |
O1 | 0.0360 (17) | 0.050 (2) | 0.0567 (19) | −0.0027 (17) | 0.0123 (14) | −0.0085 (17) |
O2 | 0.049 (2) | 0.0325 (19) | 0.103 (3) | 0.0025 (18) | 0.031 (2) | 0.006 (2) |
O3 | 0.077 (3) | 0.082 (3) | 0.066 (2) | −0.012 (3) | 0.023 (2) | −0.029 (3) |
O4 | 0.123 (4) | 0.152 (6) | 0.112 (4) | −0.020 (5) | 0.066 (3) | −0.052 (4) |
O5 | 0.0420 (19) | 0.060 (2) | 0.066 (2) | 0.006 (2) | 0.0232 (16) | −0.005 (2) |
O6 | 0.049 (2) | 0.068 (3) | 0.065 (2) | 0.007 (2) | 0.0185 (17) | 0.023 (2) |
N1 | 0.0327 (19) | 0.043 (2) | 0.0426 (19) | 0.005 (2) | 0.0116 (16) | 0.004 (2) |
N2 | 0.038 (2) | 0.056 (3) | 0.045 (2) | −0.001 (2) | 0.0169 (17) | 0.003 (2) |
C1 | 0.035 (2) | 0.037 (3) | 0.053 (3) | 0.001 (2) | 0.008 (2) | −0.008 (2) |
C2 | 0.038 (3) | 0.046 (3) | 0.070 (3) | 0.001 (3) | 0.010 (2) | −0.009 (3) |
C3 | 0.034 (2) | 0.036 (3) | 0.080 (4) | 0.004 (2) | 0.016 (2) | −0.005 (3) |
C4 | 0.043 (3) | 0.035 (3) | 0.069 (3) | 0.009 (2) | 0.019 (2) | −0.002 (3) |
C5 | 0.070 (4) | 0.068 (4) | 0.073 (4) | −0.010 (4) | 0.029 (3) | −0.018 (4) |
C6 | 0.086 (5) | 0.070 (4) | 0.059 (3) | 0.010 (4) | 0.016 (3) | −0.015 (4) |
C7 | 0.086 (4) | 0.064 (4) | 0.051 (3) | 0.007 (4) | 0.002 (3) | −0.006 (3) |
C8 | 0.120 (6) | 0.074 (5) | 0.067 (4) | 0.019 (5) | 0.004 (4) | −0.017 (4) |
C9 | 0.162 (10) | 0.078 (6) | 0.083 (5) | −0.003 (8) | −0.023 (6) | −0.019 (5) |
C10 | 0.129 (9) | 0.089 (7) | 0.108 (7) | −0.027 (7) | −0.037 (6) | −0.003 (7) |
C11 | 0.090 (5) | 0.096 (7) | 0.101 (5) | −0.020 (6) | −0.005 (4) | 0.005 (5) |
C12 | 0.080 (5) | 0.075 (5) | 0.071 (4) | −0.002 (4) | 0.008 (3) | −0.005 (4) |
C13 | 0.036 (2) | 0.044 (3) | 0.048 (2) | 0.008 (2) | 0.017 (2) | 0.006 (2) |
C14 | 0.036 (2) | 0.043 (3) | 0.047 (2) | 0.007 (3) | 0.014 (2) | 0.010 (3) |
C15 | 0.033 (2) | 0.043 (3) | 0.049 (3) | 0.000 (3) | 0.011 (2) | −0.003 (3) |
C16 | 0.030 (2) | 0.045 (3) | 0.048 (3) | −0.002 (2) | 0.006 (2) | 0.004 (3) |
F1—C14 | 1.344 (6) | C3—H3 | 0.980 |
O1—C1 | 1.404 (5) | C4—C5 | 1.469 (7) |
O1—C4 | 1.450 (6) | C4—H4 | 0.980 |
O2—C3 | 1.441 (6) | C5—H5A | 0.970 |
O2—C2 | 1.452 (7) | C5—H5B | 0.970 |
O3—C6 | 1.315 (7) | C6—C7 | 1.484 (10) |
O3—C5 | 1.445 (8) | C7—C8 | 1.378 (9) |
O4—C6 | 1.197 (8) | C7—C12 | 1.382 (9) |
O5—C15 | 1.238 (6) | C8—C9 | 1.396 (12) |
O6—C16 | 1.208 (6) | C8—H8 | 0.930 |
N1—C13 | 1.370 (6) | C9—C10 | 1.345 (12) |
N1—C16 | 1.377 (6) | C9—H9 | 0.930 |
N1—C1 | 1.453 (6) | C10—C11 | 1.377 (13) |
N2—C15 | 1.372 (6) | C10—H10 | 0.930 |
N2—C16 | 1.384 (6) | C11—C12 | 1.381 (10) |
N2—H2 | 0.860 | C11—H11 | 0.930 |
C1—C2 | 1.507 (7) | C12—H12 | 0.930 |
C1—H1 | 0.980 | C13—C14 | 1.341 (7) |
C2—C3 | 1.457 (7) | C13—H13 | 0.930 |
C2—H2A | 0.980 | C14—C15 | 1.420 (6) |
C3—C4 | 1.506 (8) | ||
C1—O1—C4 | 109.0 (3) | O3—C5—H5B | 110.3 |
C3—O2—C2 | 60.5 (3) | C4—C5—H5B | 110.3 |
C6—O3—C5 | 118.3 (5) | H5A—C5—H5B | 108.6 |
C13—N1—C16 | 121.9 (4) | O4—C6—O3 | 122.9 (7) |
C13—N1—C1 | 119.7 (4) | O4—C6—C7 | 124.9 (6) |
C16—N1—C1 | 118.2 (4) | O3—C6—C7 | 112.2 (5) |
C15—N2—C16 | 127.1 (4) | C8—C7—C12 | 119.7 (7) |
C15—N2—H2 | 116.5 | C8—C7—C6 | 118.3 (7) |
C16—N2—H2 | 116.5 | C12—C7—C6 | 122.0 (6) |
O1—C1—N1 | 108.3 (3) | C7—C8—C9 | 120.0 (8) |
O1—C1—C2 | 105.7 (4) | C7—C8—H8 | 120.0 |
N1—C1—C2 | 115.2 (4) | C9—C8—H8 | 120.0 |
O1—C1—H1 | 109.2 | C10—C9—C8 | 119.6 (9) |
N1—C1—H1 | 109.2 | C10—C9—H9 | 120.2 |
C2—C1—H1 | 109.2 | C8—C9—H9 | 120.2 |
O2—C2—C3 | 59.4 (3) | C9—C10—C11 | 121.1 (10) |
O2—C2—C1 | 112.1 (4) | C9—C10—H10 | 119.5 |
C3—C2—C1 | 105.2 (4) | C11—C10—H10 | 119.5 |
O2—C2—H2A | 121.3 | C10—C11—C12 | 120.0 (9) |
C3—C2—H2A | 121.3 | C10—C11—H11 | 120.0 |
C1—C2—H2A | 121.3 | C12—C11—H11 | 120.0 |
O2—C3—C2 | 60.1 (4) | C11—C12—C7 | 119.6 (7) |
O2—C3—C4 | 112.7 (4) | C11—C12—H12 | 120.2 |
C2—C3—C4 | 108.3 (4) | C7—C12—H12 | 120.2 |
O2—C3—H3 | 120.3 | C14—C13—N1 | 120.6 (4) |
C2—C3—H3 | 120.3 | C14—C13—H13 | 119.7 |
C4—C3—H3 | 120.3 | N1—C13—H13 | 119.7 |
O1—C4—C5 | 109.0 (4) | C13—C14—F1 | 120.8 (4) |
O1—C4—C3 | 102.8 (4) | C13—C14—C15 | 122.1 (4) |
C5—C4—C3 | 115.5 (5) | F1—C14—C15 | 117.1 (4) |
O1—C4—H4 | 109.7 | O5—C15—N2 | 122.3 (4) |
C5—C4—H4 | 109.7 | O5—C15—C14 | 124.3 (5) |
C3—C4—H4 | 109.7 | N2—C15—C14 | 113.4 (4) |
O3—C5—C4 | 107.0 (5) | O6—C16—N1 | 124.0 (5) |
O3—C5—H5A | 110.3 | O6—C16—N2 | 121.3 (4) |
C4—C5—H5A | 110.3 | N1—C16—N2 | 114.7 (4) |
C4—O1—C1—N1 | −154.4 (4) | O3—C6—C7—C8 | 167.2 (6) |
C4—O1—C1—C2 | −30.4 (5) | O4—C6—C7—C12 | 168.3 (8) |
C13—N1—C1—O1 | 57.7 (5) | O3—C6—C7—C12 | −11.5 (9) |
C16—N1—C1—O1 | −126.0 (5) | C12—C7—C8—C9 | 1.9 (10) |
C13—N1—C1—C2 | −60.3 (5) | C6—C7—C8—C9 | −176.9 (7) |
C16—N1—C1—C2 | 115.9 (5) | C7—C8—C9—C10 | −1.9 (13) |
C3—O2—C2—C1 | 95.1 (5) | C8—C9—C10—C11 | 1.2 (15) |
O1—C1—C2—O2 | −44.1 (5) | C9—C10—C11—C12 | −0.4 (14) |
N1—C1—C2—O2 | 75.4 (5) | C10—C11—C12—C7 | 0.4 (11) |
O1—C1—C2—C3 | 18.6 (5) | C8—C7—C12—C11 | −1.1 (10) |
N1—C1—C2—C3 | 138.1 (4) | C6—C7—C12—C11 | 177.6 (6) |
C2—O2—C3—C4 | −98.7 (5) | C16—N1—C13—C14 | −0.3 (7) |
C1—C2—C3—O2 | −107.0 (4) | C1—N1—C13—C14 | 175.8 (5) |
O2—C2—C3—C4 | 106.2 (4) | N1—C13—C14—F1 | 178.3 (4) |
C1—C2—C3—C4 | −0.8 (6) | N1—C13—C14—C15 | −1.3 (8) |
C1—O1—C4—C5 | 152.3 (5) | C16—N2—C15—O5 | 175.0 (5) |
C1—O1—C4—C3 | 29.2 (5) | C16—N2—C15—C14 | −5.4 (7) |
O2—C3—C4—O1 | 48.0 (5) | C13—C14—C15—O5 | −176.5 (5) |
C2—C3—C4—O1 | −16.5 (5) | F1—C14—C15—O5 | 3.8 (7) |
O2—C3—C4—C5 | −70.6 (6) | C13—C14—C15—N2 | 3.9 (7) |
C2—C3—C4—C5 | −135.1 (5) | F1—C14—C15—N2 | −175.8 (4) |
C6—O3—C5—C4 | 144.5 (5) | C13—N1—C16—O6 | −180.0 (5) |
O1—C4—C5—O3 | 58.9 (6) | C1—N1—C16—O6 | 3.9 (7) |
C3—C4—C5—O3 | 174.1 (5) | C13—N1—C16—N2 | −0.8 (6) |
C5—O3—C6—O4 | −1.3 (10) | C1—N1—C16—N2 | −176.9 (4) |
C5—O3—C6—C7 | 178.5 (6) | C15—N2—C16—O6 | −176.8 (5) |
O4—C6—C7—C8 | −13.0 (11) | C15—N2—C16—N1 | 3.9 (7) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O5i | 0.86 | 2.01 | 2.846 (5) | 165 |
Symmetry code: (i) −x+2, y+1/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C16H13FN2O6 |
Mr | 348.28 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 298 |
a, b, c (Å) | 7.3537 (8), 5.5149 (8), 19.290 (2) |
β (°) | 100.928 (9) |
V (Å3) | 768.13 (17) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.32 × 0.20 × 0.07 |
Data collection | |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | ψ scan (XPREP; Bruker, 2001) |
Tmin, Tmax | 0.834, 0.981 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3910, 1839, 980 |
Rint | 0.048 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.052, 0.151, 1.05 |
No. of reflections | 1839 |
No. of parameters | 227 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.27, −0.27 |
Computer programs: XSCANS (Bruker, 1996), XSCANS, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), XP (Bruker, 2001), SHELXL97.
O1—C1 | 1.404 (5) | N1—C1 | 1.453 (6) |
O1—C4 | 1.450 (6) | C1—C2 | 1.507 (7) |
O2—C3 | 1.441 (6) | C2—C3 | 1.457 (7) |
O2—C2 | 1.452 (7) | C3—C4 | 1.506 (8) |
O3—C5 | 1.445 (8) | C4—C5 | 1.469 (7) |
C1—O1—C4 | 109.0 (3) | O2—C2—C3 | 59.4 (3) |
C3—O2—C2 | 60.5 (3) | C3—C2—C1 | 105.2 (4) |
O1—C1—N1 | 108.3 (3) | O2—C3—C2 | 60.1 (4) |
O1—C1—C2 | 105.7 (4) | C2—C3—C4 | 108.3 (4) |
N1—C1—C2 | 115.2 (4) | O1—C4—C3 | 102.8 (4) |
C4—O1—C1—C2 | −30.4 (5) | C1—O1—C4—C3 | 29.2 (5) |
C13—N1—C1—O1 | 57.7 (5) | C2—C3—C4—O1 | −16.5 (5) |
C16—N1—C1—O1 | −126.0 (5) | O1—C4—C5—O3 | 58.9 (6) |
O1—C1—C2—C3 | 18.6 (5) | C3—C4—C5—O3 | 174.1 (5) |
C1—C2—C3—C4 | −0.8 (6) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O5i | 0.86 | 2.01 | 2.846 (5) | 165 |
Symmetry code: (i) −x+2, y+1/2, −z. |
2',3'-Anhydro-β-D-lyxofuranosyl nucleosides are important intermediates in the synthesis of nucleoside derivatives. Modification of these structures can be readily done through reactions involving the epoxide moiety (Huryn & Okabe, 1992; Roussev et al., 1997; Miah et al., 1998; Hirota et al., 1999; Hirota et al., 2000). Because nucleophilic opening of the epoxide ring in these compounds usually proceeds such that the nucleophile attacks regioselectively at C3', they have found particular application in the synthesis of β-arabinofuranosyl nucleosides (Codington et al., 1962; Hollenberg et al., 1977). Some 2',3'-anhydro-β-D-lyxofuranosyl nucleosides, or their corresponding 5' triphosphates, have also been shown to possess antiviral activity (Krayevsky et al., 1988; Dimoglo et al., 1997; Webb et al., 1988).
We have recently developed a highly convergent method for the synthesis of 2',3'-anhydro-β-D-lyxofuranosyl nucleosides that proceeds via the coupling of glycosyl sulfoxide (II) and a silylated nucleoside base, e.g. (III), mediated by trifluoromethanesulfonic acid anhydride (Callam et al., 2003). This approach is significantly more efficient than previously developed methods for the synthesis of compounds of this type, of which all have involved the installation of the epoxide ring on a preformed nucleoside. However, unambiguously determining the stereochemistry at the anomeric center in (I) was not possible using NMR spectroscopy and we therefore crystallized this compound so that the structure could be proven. The key issue was the relative stereochemistry between the epoxide oxygen and the nucleoside base.
The structure of (I) in the crystal is given in Fig. 1 and it is clear that there is a cis relationship between the nucleoside base and the epoxide oxygen. This is the relative stereochemistry that would have been predicted for a product formed by condensation of (II) and (III), given previous results on the glycosylation of alcohols by (II) (Gadikota et al., 2003). Note also that the absolute configuration for the structure was assigned on the basis of the known configuration of (II), which was synthesized from D-arabinose (Gadikota et al., 2003). The furanose ring in (I) adopts an envelope conformation, in which the ring oxygen is displaced above the plane (°E). The pseudorotational phase angle (P) is 88.5° and the puckering amplitude (τm) is 29.8° (Altona & Sundaralingam, 1972). In this regard, the structure is similar to other 2',3'-anhydro-β-D-lyxofuranosyl nucleotides for which crystal structures have been determined, e.g. (IV) and (V) (Gurskaya et al., 1990, 1996) or for which molecular-mechanics calculations have been carried out, e.g. (IV), (VI) and (VII) (Koole et al., 1991). In these compounds, the furanose and epoxide O atoms are on the same side of the furanose ring, resulting in a boat-like structure. In addition, the five-membered rings in these systems are generally less puckered than other nucleoside derivatives, which typically have τm magnitudes in the range 34–40° (Sanger, 1984). Similar structural features have been observed in ab initio and density functional theory calculations on 2,3-anhydro-β-D-lyxofuranosyl glycosides (Callam et al., 2001) and in the crystal structure of a 2,3-anhydro-α-D-lyxofuranosyl thioglycoside (Gallucci et al., 2000).
The orientation about the C4—C5 bond in (I) is gauche–trans (ap) (Sanger, 1984). This bond adopts the same orientation in the crystal structure of (IV) and in low-energy geometries obtained from molecular mechanics calculations of (IV), (VI) and (VII), thus indicating that the presence of the benozate ester on O3 in (I) does not alter the favored rotamer around the C4–C5 bond, as compared to the unprotected nucleosides. In the crystal structure of (V), however, the orientation of this bond differs from that in (I), (IV), (VI) and (VII), which is likely due to the presence of the additional hydroxymethyl group substituent at C4. Finally, in (I) the nucleoside base adopts the anti-conformation, which is the same as in compounds (IV)–(VII).