(3S,2R)-3-Hydro­xy-2-hydroxy­methyl-7,9-di­aza­spiro­[4.5]­decane-6,8,10-trione

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.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](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

---

S1. Comment

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.

S2. Experimental

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): R_f 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. 1}H 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.

S3. Refinement

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.

Computing details

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.

Figures

Fig. 1. ORTEPII (Johnson, 1976) molecular diagram of title compound. Ellipsoids are shown at the 25% probability level.

(I)

Crystal data

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) Å^3	0.32 × 0.16 × 0.09 mm
Z = 2

Data collection

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

Refinement on F	0 restraints
Least-squares matrix: full	0 constraints
R[F^2 > 2σ(F^2)] = 0.039	H-atom parameters not refined
wR(F^2) = 0.044	Weighting scheme based on measured s.u.'s w = 1/[σ^2(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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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···N9^i	2.862 (1)	O6···O11^iv	2.809 (2)
O2···O8^ii	3.111 (1)	O10···N7^v	2.840 (2)
O2···O10^i	3.131 (2)	O11···C10^vi	2.975 (2)
O2···N7^iii	3.143 (2)	O11···N9^vi	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)

D—H···A	D—H	H···A	D···A	D—H···A
O11—H12···O6^v	0.81	2.00	2.809 (2)	173
N7—H8···O10^iv	0.86	1.99	2.840 (2)	170
N9—H9···O2^vii	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.