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The trans stereochemical relationship of the two substituents of the title compound, C9H12N2O5, a new spiro-nucleoside, has been confirmed. The cyclopentane moiety adopts the C3'-endo-type conformation, while the barbiturate ring is almost planar. Molecules interconnected by a two-dimensional network of hydrogen bonds build layers parallel to the ab plane.
Supporting information
CCDC reference: 182610
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.002 Å
- R factor = 0.039
- wR factor = 0.044
- Data-to-parameter ratio = 12.5
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
Alert Level C:
PLAT_162 Alert C Missing or Zero su (esd) on y-coordinate for . O2
General Notes
REFLT_03
From the CIF: _diffrn_reflns_theta_max 35.00
From the CIF: _reflns_number_total 2187
Count of symmetry unique reflns 2191
Completeness (_total/calc) 99.82%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 0
Fraction of Friedel pairs measured 0.000
Are heavy atom types Z>Si present no
Please check that the estimate of the number of Friedel pairs is
correct. If it is not, please give the correct count in the
_publ_section_exptl_refinement section of the submitted CIF.
0 Alert Level A = Potentially serious problem
0 Alert Level B = Potential problem
1 Alert Level C = Please check
The title compound was prepared according to the process decribed by Renard
et al. (2002). To a solution of
3',5'-O-bis(tert-butyldimethylsilyl)spirocyclopentylbarbituric
acid (2.0 g, 4.4 mmol) in MeOH (10 ml) was added TMSCl (500 µl). This
solution was stirred at room temperature for 15 min while the deprotected
spirocyclopentylbarbituric acid precipitated in the medium. The volatile
material was removed under reduced pressure and the resulting residue was
triturated into Et2O as to afford a white powder (1.0 g, 4.3 mmol, 99%; m.p.
487–489 K). TLC (MeOH/CH2Cl2 20:80): Rf 0.28. [α]D25 =
+34.8 (c = 0.91, MeOH). IR (KBr): ν 3351, 3197, 3076, 2844, 1754, 1740, 1689,
1444, 1352, 1175, 1081, 807 cm-1. 1H NMR (200 MHz, [D6]DMSO): δ
1.65–2.30 (m, 5H, H-2', H-4', H-6'), 3.31 (m, 1H, H-5'), 3.56 (m, 1H, H-5'),
3.82 (m, 1H, H-3'), 4.42 (m, OH-5'), 4.84 (m, OH-3'), 11.0 (br s, 2H, NH).
13C NMR (50 MHz, [D6]DMSO): δ = 37.9 (C-6'), 42.5 (C-2'),49.0 (C-4'),
51.9 (C-1'), 61.3 (C-5'), 72.5 (C-3'), 150.5 (C═O), 174.6 (C═O). MS
(FAB–, glycerol): m/z: 227 [M—H]. Analysis for C9H12N2O5
(228.20), calculated: C 47.37, H 5.30, N 12.28%; found: C 47.46, H 5.46, N
12.27%. Crystals were obtained by slow evaporation of a solution in water.
The H atoms located on CH bonds were placed by geometry whereas H atoms located
on OH or NH bonds were placed from a difference Fourier map; in both cases,
they were not refined. Since there is a twofold screw axis, in order to avoid
any remaining shifts, we choose to fix as an origin the heaviest atom O2 and
to fix its y coordinate instead of fixing the sum of coordinates.
Because of the lack of any significant anomalous dispersion effects, the
absolute configuration can not be determined from the diffraction experiment.
Friedel pairs in the data set have been merged prior to refinement.
Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: TEXSAN (Molecular Structure Corporation, 1992-1997); program(s) used to solve structure: SIR 92 (Altomare et al., 1994); program(s) used to refine structure: TEXSAN; software used to prepare material for publication: TEXSAN.
Crystal data top
C9H12N2O5 | F(000) = 240.00 |
Mr = 228.20 | Dx = 1.623 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.7107 Å |
Hall symbol: P 2yb | Cell parameters from 25 reflections |
a = 7.467 (2) Å | θ = 9.3–12.7° |
b = 6.802 (1) Å | µ = 0.13 mm−1 |
c = 9.673 (3) Å | T = 293 K |
β = 108.07 (2)° | Monoclinic prism, colorless |
V = 467.1 (2) Å3 | 0.32 × 0.16 × 0.09 mm |
Z = 2 | |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.014 |
Radiation source: X-ray tube | θmax = 35°, θmin = 2° |
Graphite monochromator | h = −12→12 |
ω scans | k = 0→11 |
2284 measured reflections | l = 0→15 |
2187 independent reflections | 2 standard reflections every 120 reflections |
1818 reflections with I > 1.5σ(I) | intensity decay: 0.2% |
Refinement top
Refinement on F | 0 restraints |
Least-squares matrix: full | 0 constraints |
R[F2 > 2σ(F2)] = 0.039 | H-atom parameters not refined |
wR(F2) = 0.044 | Weighting scheme based on measured s.u.'s w = 1/[σ2(Fo) + 0.00006|Fo|2] |
S = 1.40 | (Δ/σ)max = 0.004 |
1817 reflections | Δρmax = 0.28 e Å−3 |
145 parameters | Δρmin = −0.22 e Å−3 |
Crystal data top
C9H12N2O5 | V = 467.1 (2) Å3 |
Mr = 228.20 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 7.467 (2) Å | µ = 0.13 mm−1 |
b = 6.802 (1) Å | T = 293 K |
c = 9.673 (3) Å | 0.32 × 0.16 × 0.09 mm |
β = 108.07 (2)° | |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.014 |
2284 measured reflections | 2 standard reflections every 120 reflections |
2187 independent reflections | intensity decay: 0.2% |
1818 reflections with I > 1.5σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.039 | 0 restraints |
wR(F2) = 0.044 | H-atom parameters not refined |
S = 1.40 | Δρmax = 0.28 e Å−3 |
1817 reflections | Δρmin = −0.22 e Å−3 |
145 parameters | |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O2 | 0.7824 (1) | 0.3538 | 0.6125 (1) | 0.0259 (2) | |
O6 | 0.5675 (2) | −0.2227 (2) | 0.7783 (2) | 0.0428 (3) | |
O8 | −0.0661 (2) | −0.2172 (2) | 0.6421 (1) | 0.0385 (3) | |
O10 | 0.2232 (2) | 0.3681 (2) | 0.7248 (2) | 0.0436 (3) | |
O11 | 0.7784 (2) | 0.5336 (2) | 1.0048 (1) | 0.0367 (3) | |
N7 | 0.2531 (2) | −0.2161 (2) | 0.7162 (1) | 0.0241 (2) | |
N9 | 0.0841 (2) | 0.0764 (2) | 0.6633 (1) | 0.0239 (2) | |
C1 | 0.5145 (2) | 0.1639 (2) | 0.6213 (1) | 0.0224 (3) | |
C2 | 0.6546 (2) | 0.3235 (2) | 0.6934 (1) | 0.0189 (2) | |
C3 | 0.7449 (2) | 0.2422 (2) | 0.8470 (1) | 0.0204 (2) | |
C4 | 0.5742 (2) | 0.1718 (2) | 0.8875 (1) | 0.0257 (3) | |
C5 | 0.4305 (2) | 0.0959 (2) | 0.7430 (1) | 0.0215 (3) | |
C6 | 0.4234 (2) | −0.1261 (2) | 0.7470 (2) | 0.0242 (3) | |
C8 | 0.0810 (2) | −0.1249 (2) | 0.6717 (1) | 0.0227 (3) | |
C10 | 0.2408 (2) | 0.1914 (2) | 0.7133 (2) | 0.0245 (3) | |
C11 | 0.8744 (2) | 0.3826 (3) | 0.9555 (1) | 0.0282 (3) | |
H1 | 0.4186 | 0.2148 | 0.5400 | 0.027* | |
H2 | 0.5761 | 0.0578 | 0.5908 | 0.027* | |
H3 | 0.5896 | 0.4423 | 0.6979 | 0.023* | |
H4 | 0.8382 | 0.4452 | 0.6366 | 0.056* | |
H5 | 0.8168 | 0.1298 | 0.8394 | 0.024* | |
H6 | 0.6088 | 0.0687 | 0.9569 | 0.031* | |
H7 | 0.5213 | 0.2772 | 0.9263 | 0.031* | |
H8 | 0.2580 | −0.3428 | 0.7191 | 0.030* | |
H9 | −0.0212 | 0.1352 | 0.6483 | 0.029* | |
H10 | 0.9571 | 0.4421 | 0.9104 | 0.034* | |
H11 | 0.9457 | 0.3087 | 1.0374 | 0.034* | |
H12 | 0.7203 | 0.5978 | 0.9343 | 0.062* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O2 | 0.0242 (4) | 0.0258 (5) | 0.0300 (4) | −0.0026 (4) | 0.0118 (3) | 0.0023 (4) |
O6 | 0.0297 (5) | 0.0229 (5) | 0.0725 (8) | 0.0084 (4) | 0.0110 (5) | 0.0050 (6) |
O8 | 0.0297 (5) | 0.0318 (6) | 0.0521 (6) | −0.0117 (5) | 0.0100 (4) | −0.0060 (6) |
O10 | 0.0374 (5) | 0.0134 (4) | 0.0834 (9) | 0.0015 (4) | 0.0236 (5) | 0.0003 (6) |
O11 | 0.0465 (6) | 0.0280 (5) | 0.0322 (5) | 0.0022 (5) | 0.0074 (5) | −0.0079 (4) |
N7 | 0.0281 (5) | 0.0114 (4) | 0.0328 (5) | −0.0026 (4) | 0.0094 (4) | −0.0001 (4) |
N9 | 0.0198 (4) | 0.0196 (5) | 0.0315 (5) | 0.0024 (4) | 0.0068 (4) | 0.0025 (5) |
C1 | 0.0227 (5) | 0.0213 (5) | 0.0226 (5) | −0.0035 (5) | 0.0063 (4) | −0.0024 (5) |
C2 | 0.0182 (4) | 0.0154 (5) | 0.0224 (5) | 0.0001 (4) | 0.0054 (4) | 0.0005 (4) |
C3 | 0.0206 (5) | 0.0178 (5) | 0.0212 (5) | 0.0008 (4) | 0.0041 (4) | −0.0002 (4) |
C4 | 0.0292 (5) | 0.0240 (6) | 0.0260 (5) | −0.0056 (5) | 0.0115 (4) | −0.0016 (5) |
C5 | 0.0209 (5) | 0.0140 (5) | 0.0302 (6) | −0.0013 (4) | 0.0088 (4) | 0.0000 (4) |
C6 | 0.0237 (5) | 0.0144 (5) | 0.0344 (6) | −0.0001 (4) | 0.0090 (4) | 0.0008 (5) |
C8 | 0.0246 (5) | 0.0199 (5) | 0.0241 (5) | −0.0026 (5) | 0.0081 (4) | −0.0017 (5) |
C10 | 0.0231 (5) | 0.0152 (5) | 0.0368 (6) | 0.0004 (4) | 0.0117 (5) | 0.0022 (5) |
C11 | 0.0243 (5) | 0.0299 (7) | 0.0264 (6) | −0.0008 (5) | 0.0023 (5) | −0.0044 (6) |
Geometric parameters (Å, º) top
O2—C2 | 1.425 (2) | C5—C6 | 1.511 (2) |
O6—C6 | 1.217 (2) | C5—C10 | 1.503 (2) |
O8—C8 | 1.219 (2) | O2—H4 | 0.74 |
O10—C10 | 1.218 (2) | O11—H12 | 0.81 |
O11—C11 | 1.417 (2) | N7—H8 | 0.86 |
N7—C6 | 1.359 (2) | N9—H9 | 0.85 |
N7—C8 | 1.371 (2) | C1—H1 | 0.95 |
N9—C8 | 1.372 (2) | C1—H2 | 0.95 |
N9—C10 | 1.365 (2) | C2—H3 | 0.95 |
C1—C2 | 1.519 (2) | C3—H5 | 0.95 |
C1—C5 | 1.566 (2) | C4—H6 | 0.95 |
C2—C3 | 1.532 (2) | C4—H7 | 0.95 |
C3—C4 | 1.523 (2) | C11—H10 | 0.95 |
C3—C11 | 1.523 (2) | C11—H11 | 0.95 |
C4—C5 | 1.563 (2) | | |
| | | |
O2···N9i | 2.862 (1) | O6···O11iv | 2.809 (2) |
O2···O8ii | 3.111 (1) | O10···N7v | 2.840 (2) |
O2···O10i | 3.131 (2) | O11···C10vi | 2.975 (2) |
O2···N7iii | 3.143 (2) | O11···N9vi | 3.066 (2) |
| | | |
C6—N7—C8 | 126.0 (1) | C11—O11—H12 | 107.5 |
C8—N9—C10 | 125.4 (1) | C6—N7—H8 | 114.6 |
C2—C1—C5 | 104.2 (1) | C8—N7—H8 | 119.3 |
O2—C2—C1 | 109.5 (1) | C8—N9—H9 | 116.5 |
O2—C2—C3 | 114.6 (1) | C10—N9—H9 | 115.8 |
C1—C2—C3 | 102.7 (1) | C2—C1—H1 | 110.8 |
C2—C3—C4 | 102.2 (1) | C2—C1—H2 | 110.8 |
C2—C3—C11 | 115.9 (1) | C5—C1—H1 | 110.8 |
C4—C3—C11 | 115.0 (1) | C5—C1—H2 | 110.8 |
C3—C4—C5 | 105.7 (1) | H1—C1—H2 | 109.5 |
C1—C5—C4 | 104.5 (1) | O2—C2—H3 | 109.9 |
C1—C5—C6 | 109.9 (1) | C1—C2—H3 | 109.9 |
C1—C5—C10 | 107.6 (1) | C3—C2—H3 | 109.9 |
C4—C5—C6 | 109.1 (1) | C2—C3—H5 | 107.8 |
C4—C5—C10 | 111.9 (1) | C4—C3—H5 | 107.8 |
C6—C5—C10 | 113.5 (1) | C11—C3—H5 | 107.8 |
O6—C6—N7 | 120.4 (1) | C3—C4—H6 | 110.4 |
O6—C6—C5 | 120.7 (1) | C3—C4—H7 | 110.4 |
N7—C6—C5 | 118.8 (1) | C5—C4—H6 | 110.4 |
O8—C8—N7 | 121.9 (1) | C5—C4—H7 | 110.4 |
O8—C8—N9 | 122.0 (1) | H6—C4—H7 | 109.5 |
N7—C8—N9 | 116.0 (1) | O11—C11—H10 | 108.3 |
O10—C10—N9 | 119.5 (1) | O11—C11—H11 | 108.3 |
O10—C10—C5 | 122.1 (1) | C3—C11—H10 | 108.3 |
N9—C10—C5 | 118.3 (1) | C3—C11—H11 | 108.3 |
O11—C11—C3 | 114.0 (1) | H10—C11—H11 | 109.5 |
C2—O2—H4 | 110.7 | | |
| | | |
O2—C2—C1—C5 | 161.56 (9) | N7—C8—N9—C10 | −9.2 (2) |
O2—C2—C3—C4 | −164.5 (1) | N9—C8—N7—C6 | −2.5 (2) |
O2—C2—C3—C11 | 69.7 (1) | N9—C10—C5—C1 | 108.0 (1) |
O6—C6—N7—C8 | −176.1 (1) | N9—C10—C5—C4 | −137.7 (1) |
O6—C6—C5—C1 | 63.8 (2) | N9—C10—C5—C6 | −13.8 (2) |
O6—C6—C5—C4 | −50.3 (2) | C1—C2—C3—C4 | −45.7 (1) |
O6—C6—C5—C10 | −175.7 (1) | C1—C2—C3—C11 | −171.6 (1) |
O8—C8—N7—C6 | 177.9 (1) | C1—C5—C4—C3 | −10.1 (1) |
O8—C8—N9—C10 | 170.4 (1) | C2—C1—C5—C4 | −18.0 (1) |
O10—C10—N9—C8 | −166.4 (2) | C2—C1—C5—C6 | −134.9 (1) |
O10—C10—C5—C1 | −68.0 (2) | C2—C1—C5—C10 | 101.1 (1) |
O10—C10—C5—C4 | 46.3 (2) | C2—C3—C4—C5 | 34.1 (1) |
O10—C10—C5—C6 | 170.3 (2) | C3—C2—C1—C5 | 39.4 (1) |
O11—C11—C3—C2 | 73.8 (2) | C3—C4—C5—C6 | 107.3 (1) |
O11—C11—C3—C4 | −45.3 (2) | C3—C4—C5—C10 | −126.3 (1) |
N7—C6—C5—C1 | −116.7 (1) | C5—C4—C3—C11 | 160.5 (1) |
N7—C6—C5—C4 | 129.3 (1) | C5—C6—N7—C8 | 4.4 (2) |
N7—C6—C5—C10 | 3.8 (2) | C5—C10—N9—C8 | 17.5 (2) |
Symmetry codes: (i) x+1, y, z; (ii) x+1, y+1, z; (iii) −x+1, y+1/2, −z+1; (iv) x, y−1, z; (v) x, y+1, z; (vi) −x+1, y+1/2, −z+2. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O11—H12···O6v | 0.81 | 2.00 | 2.809 (2) | 173 |
N7—H8···O10iv | 0.86 | 1.99 | 2.840 (2) | 170 |
N9—H9···O2vii | 0.85 | 2.04 | 2.862 (1) | 161 |
Symmetry codes: (iv) x, y−1, z; (v) x, y+1, z; (vii) x−1, y, z. |
Experimental details
Crystal data |
Chemical formula | C9H12N2O5 |
Mr | 228.20 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 7.467 (2), 6.802 (1), 9.673 (3) |
β (°) | 108.07 (2) |
V (Å3) | 467.1 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.13 |
Crystal size (mm) | 0.32 × 0.16 × 0.09 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 1.5σ(I)] reflections | 2284, 2187, 1818 |
Rint | 0.014 |
(sin θ/λ)max (Å−1) | 0.807 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.044, 1.40 |
No. of reflections | 1817 |
No. of parameters | 145 |
H-atom treatment | H-atom parameters not refined |
Δρmax, Δρmin (e Å−3) | 0.28, −0.22 |
Selected geometric parameters (Å, º) topO2—C2 | 1.425 (2) | C1—C2 | 1.519 (2) |
O6—C6 | 1.217 (2) | C1—C5 | 1.566 (2) |
O8—C8 | 1.219 (2) | C2—C3 | 1.532 (2) |
O10—C10 | 1.218 (2) | C3—C4 | 1.523 (2) |
O11—C11 | 1.417 (2) | C3—C11 | 1.523 (2) |
N7—C6 | 1.359 (2) | C4—C5 | 1.563 (2) |
N7—C8 | 1.371 (2) | C5—C6 | 1.511 (2) |
N9—C8 | 1.372 (2) | C5—C10 | 1.503 (2) |
N9—C10 | 1.365 (2) | | |
| | | |
C6—N7—C8 | 126.0 (1) | C4—C5—C6 | 109.1 (1) |
C8—N9—C10 | 125.4 (1) | C4—C5—C10 | 111.9 (1) |
C2—C1—C5 | 104.2 (1) | C6—C5—C10 | 113.5 (1) |
O2—C2—C1 | 109.5 (1) | O6—C6—N7 | 120.4 (1) |
O2—C2—C3 | 114.6 (1) | O6—C6—C5 | 120.7 (1) |
C1—C2—C3 | 102.7 (1) | N7—C6—C5 | 118.8 (1) |
C2—C3—C4 | 102.2 (1) | O8—C8—N7 | 121.9 (1) |
C2—C3—C11 | 115.9 (1) | O8—C8—N9 | 122.0 (1) |
C4—C3—C11 | 115.0 (1) | N7—C8—N9 | 116.0 (1) |
C3—C4—C5 | 105.7 (1) | O10—C10—N9 | 119.5 (1) |
C1—C5—C4 | 104.5 (1) | O10—C10—C5 | 122.1 (1) |
C1—C5—C6 | 109.9 (1) | N9—C10—C5 | 118.3 (1) |
C1—C5—C10 | 107.6 (1) | O11—C11—C3 | 114.0 (1) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O11—H12···O6i | 0.81 | 2.00 | 2.809 (2) | 172.8 |
N7—H8···O10ii | 0.86 | 1.99 | 2.840 (2) | 170.1 |
N9—H9···O2iii | 0.85 | 2.04 | 2.862 (1) | 161.0 |
Symmetry codes: (i) x, y+1, z; (ii) x, y−1, z; (iii) x−1, y, z. |
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Among many modified nucleosides exhibiting biological activities, some spiro-nucleosides have been shown to be useful as potent herbicide without animal toxicity. Synthetic efforts have been devoted in recent years to their analogues (Mio & Sano, 1997; Nakajima et al., 1991). We are interested in the highly constrained structural feature of these spiro-nucleosides which may be used as promising building units for modified oligonucleotide synthesis in the antisense and/or the antigene strategy. It is well established that conformational restriction may lead to favourable complex formation due to an entropic advantage. This concept has been investigated quite intensively in nucleoside and especially oligonucleotide chemistry (Meldgaard & Wengel, 2000). Recently, we have developed synthetic methods for new carbocyclic spiro-nucleosides containing barbituric acid moiety (1) using the synthetic scheme below (Renard et al., 2002). The reagents and conditions are as follows: (a) (CH2O)n, AcOH, H2SO4, 333 K, 24 h; (b) TMSCl, MeOH; (c) resolution; (d) TBDMSCl, imidazole; (e) urea, tBuOK; (f) TMSCl, MeOH.
We have shown that the spiro-nucleoside (1) is considerably more stable against ring opening than the deoxyribosyl derivative (2). Also these compounds present enhanced hydrogen bonding capacity with `complementary' deoxyadenosine derivative. So it is interesting to determine the three-dimensional structure and hydrogen-bonding features of this spiro-nucleoside.
The present atomic arrangement is a typical layer organization. Molecules of the title compound interconnected by N—H···O and O—H···O hydrogen bonds build up layers parallel to the ab planes. In the present compound, as expected, the barbiturate ring is quasi-planar. The largest deviation from its least-squares plane is 0.102 (2) Å for C10. It is also worth noticing the relatively high density (1.623 Mg m-3) of this compound.