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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o853.
Published online 2010 March 17. doi:  10.1107/S1600536810009165
PMCID: PMC2983886

(1R,2R,3S,6aS,7R,8R,9S,12aS)-1,2,3,7,8,9-Hexahydroxy­perhydro­dipyrido[1,2-a:1′,2′-d]pyrazine-6,12-dione

Abstract

The crystal structure of the title compound, C12H18N2O8, exists as O—H(...)O hydrogen-bonded layers of mol­ecules running parallel to the ab plane. Each mol­ecule is a donor and acceptor for six hydrogen bonds. The absolute stereochemistry was determined by the use of d-glucuronolactone as the starting material.

Related literature

For the isolation and biological activity of pipecolic acids, see: Manning et al. (1985 [triangle]); di Bello et al. (1984 [triangle]). For the synthesis of pipecolic acids, see: Bashyal et al. (1986 [triangle]); Bashyal, Chow & Fleet (1987 [triangle]); Bashyal, Chow, Fellows & Fleet (1987 [triangle]).

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Object name is e-66-0o853-scheme1.jpg

Experimental

Crystal data

  • C12H18N2O8
  • M r = 318.28
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o853-efi1.jpg
  • a = 7.8711 (2) Å
  • b = 8.1526 (2) Å
  • c = 19.5783 (5) Å
  • V = 1256.34 (5) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.14 mm−1
  • T = 150 K
  • 0.40 × 0.10 × 0.10 mm

Data collection

  • Nonius KappaCCD area-detector diffractometer
  • Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 [triangle]) T min = 0.85, T max = 0.99
  • 12748 measured reflections
  • 1663 independent reflections
  • 1348 reflections with I > 2σ(I)
  • R int = 0.061

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.101
  • S = 0.93
  • 1662 reflections
  • 199 parameters
  • H-atom parameters constrained
  • Δρmax = 0.35 e Å−3
  • Δρmin = −0.43 e Å−3

Data collection: COLLECT (Nonius, 2001 [triangle]); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 [triangle]); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 [triangle]); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 [triangle]); molecular graphics: CAMERON (Watkin et al., 1996 [triangle]); software used to prepare material for publication: CRYSTALS.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810009165/lh5005sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810009165/lh5005Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

We would like to thank the Chemical Crystallography department and ALT at the University of Oxford for use of the diffractometers.

supplementary crystallographic information

Comment

2S,3R,4R,5S-Trihydroxypipecolicacid (BR1) 2 (Fig.1), a sugar mimic of glucuronic acid, has been isolated from the seeds of Baphia racemosa (Manning et al., 1985) and shown to inhibit both glucuronidase and iduronidase activity (di Bello et al., 1984). In a modification of the original synthesis of BR1 from D-glucuronolactone (Bashyal et al., 1986, Bashyal, Chow & Fleet, 1987, Bashyal, Chow, Fellows & Fleet, 1987), reduction of the azide 1 afforded a low yield of 2 together with by-products. One of the components of the mixture was crystallized; the structure of this material was determined unequivocally by X-ray crystallographic analysis and shown to be the diketopiperazine 3 (Fig. 2). The absolute stereochemistry was determined by the use of D-glucuronolactone as the starting material. The structure consists of layers of hydrogen bonded molecules running parallel to the ab plane (Fig. 3, Fig. 4). Each molecule is a donor and acceptor for 6 hydrogen bonds. Only classical hydrogen bonding was considered.

Experimental

The title compound was recrystallised by diffusion from a mixture of water and acetonitrile: m.p. 511 K decomposed; [α]D20 + 29.7 (c, 0.35 in H2O).

Refinement

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration was assigned from the starting material.

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, N—H in the range 0.86–0.89 N—H to 0.86 O—H = 0.82 Å) and Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom), after which the positions were refined with riding constraints.

One outlying reflection was omitted from the refinement as it was thought to be partially occluded by the beam stop.

Figures

Fig. 1.
Synthetic Scheme.
Fig. 2.
The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
Fig. 3.
Packing diagram for the title compound projected along the a-axis. Hydrogen bonds are shown by dotted lines.
Fig. 4.
Packing diagram for the title compound projected along the b axis. Hydrogen bonds are shown by dotted lines.

Crystal data

C12H18N2O8F(000) = 672
Mr = 318.28Dx = 1.683 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 1646 reflections
a = 7.8711 (2) Åθ = 5–27°
b = 8.1526 (2) ŵ = 0.14 mm1
c = 19.5783 (5) ÅT = 150 K
V = 1256.34 (5) Å3Plate, colourless
Z = 40.40 × 0.10 × 0.10 mm

Data collection

Nonius KappaCCD area-detector diffractometer1348 reflections with I > 2σ(I)
graphiteRint = 0.061
ω scansθmax = 27.5°, θmin = 5.1°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)h = −10→10
Tmin = 0.85, Tmax = 0.99k = −10→10
12748 measured reflectionsl = −25→25
1663 independent reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.101 Method = Modified Sheldrick w = 1/[σ2(F2) + (0.06P)2 + 0.76P], where P = [max(Fo2,0) + 2Fc2]/3
S = 0.93(Δ/σ)max = 0.0003
1662 reflectionsΔρmax = 0.35 e Å3
199 parametersΔρmin = −0.43 e Å3
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.4593 (3)0.7922 (2)0.34949 (10)0.0245
C20.5380 (4)0.6635 (3)0.34006 (13)0.0181
N30.6870 (3)0.6583 (3)0.30476 (12)0.0186
C40.8001 (3)0.5165 (3)0.30769 (13)0.0178
C50.9227 (3)0.5430 (3)0.36900 (14)0.0187
O61.0531 (3)0.4227 (2)0.36945 (10)0.0233
C71.0081 (4)0.7115 (3)0.36672 (14)0.0191
O81.0852 (2)0.7438 (2)0.43187 (9)0.0238
C90.8851 (4)0.8502 (3)0.35308 (14)0.0196
C100.7767 (4)0.8115 (4)0.29066 (15)0.0202
O110.9812 (3)0.9966 (2)0.34507 (10)0.0247
C120.7057 (4)0.3552 (3)0.31154 (14)0.0192
O130.7761 (3)0.2272 (2)0.29231 (10)0.0234
N140.5463 (3)0.3566 (3)0.33597 (12)0.0186
C150.4689 (3)0.5025 (3)0.36625 (13)0.0188
C160.4834 (3)0.4874 (3)0.44528 (13)0.0187
O170.3887 (3)0.6143 (2)0.47677 (10)0.0240
C180.4098 (4)0.3245 (3)0.46900 (13)0.0203
O190.4442 (3)0.3016 (3)0.54059 (9)0.0269
C200.4757 (4)0.1754 (3)0.43053 (13)0.0201
C210.4581 (4)0.2045 (3)0.35390 (13)0.0199
O220.3776 (3)0.0390 (2)0.45221 (10)0.0310
H410.86550.51500.26560.0187*
H510.85350.53360.41090.0227*
H711.09740.71160.33160.0230*
H910.80580.86050.39270.0225*
H1020.84590.79640.25090.0230*
H1010.69750.89900.28350.0223*
H1510.34430.50030.35570.0220*
H1610.60540.49420.45880.0216*
H1810.28250.32830.46340.0238*
H2010.59960.15980.44170.0244*
H2120.50770.11180.32860.0232*
H2110.33490.21630.34330.0228*
H811.18090.70270.43650.0340*
H2210.3488−0.02990.42310.0459*
H1910.48420.38320.55890.0407*
H1110.91141.06450.33110.0377*
H1710.43380.68040.50130.0351*
H611.06600.35930.40210.0354*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0253 (11)0.0201 (10)0.0280 (11)0.0043 (9)0.0024 (9)−0.0012 (8)
C20.0189 (14)0.0226 (14)0.0128 (13)0.0006 (13)−0.0029 (11)−0.0002 (10)
N30.0185 (12)0.0171 (11)0.0203 (13)0.0000 (10)0.0012 (10)0.0030 (9)
C40.0153 (12)0.0194 (13)0.0186 (13)0.0024 (12)0.0012 (10)0.0011 (11)
C50.0174 (13)0.0198 (13)0.0188 (13)0.0017 (11)0.0017 (11)0.0014 (10)
O60.0206 (10)0.0224 (10)0.0270 (10)0.0069 (9)−0.0006 (9)0.0050 (9)
C70.0193 (14)0.0209 (13)0.0170 (13)0.0003 (11)0.0006 (11)−0.0014 (11)
O80.0191 (10)0.0316 (11)0.0208 (10)0.0048 (9)−0.0041 (8)−0.0056 (8)
C90.0191 (14)0.0192 (14)0.0205 (14)−0.0001 (12)0.0020 (11)−0.0008 (10)
C100.0200 (15)0.0205 (13)0.0203 (15)0.0011 (12)−0.0010 (11)0.0004 (11)
O110.0265 (10)0.0169 (10)0.0307 (10)0.0000 (10)−0.0056 (8)0.0012 (8)
C120.0212 (14)0.0235 (15)0.0129 (14)0.0016 (12)−0.0019 (11)0.0007 (11)
O130.0274 (12)0.0206 (10)0.0223 (11)0.0049 (9)0.0016 (9)−0.0027 (8)
N140.0182 (12)0.0180 (12)0.0197 (12)−0.0009 (11)0.0002 (10)−0.0004 (9)
C150.0168 (12)0.0208 (14)0.0186 (12)0.0026 (13)0.0021 (10)−0.0015 (12)
C160.0151 (12)0.0214 (14)0.0197 (12)0.0014 (12)0.0006 (10)−0.0017 (11)
O170.0259 (11)0.0240 (10)0.0220 (10)0.0037 (9)0.0005 (9)−0.0075 (8)
C180.0182 (14)0.0270 (14)0.0158 (14)0.0028 (12)−0.0007 (11)0.0015 (11)
O190.0392 (12)0.0261 (10)0.0153 (9)0.0003 (10)−0.0045 (9)0.0013 (8)
C200.0200 (13)0.0183 (13)0.0220 (14)−0.0013 (12)0.0010 (11)0.0007 (11)
C210.0195 (14)0.0200 (14)0.0201 (14)−0.0034 (12)0.0015 (12)−0.0005 (11)
O220.0468 (13)0.0227 (11)0.0235 (10)−0.0087 (10)0.0064 (10)−0.0005 (8)

Geometric parameters (Å, °)

O1—C21.232 (3)O11—H1110.826
C2—N31.362 (4)C12—O131.240 (3)
C2—C151.510 (4)C12—N141.343 (4)
N3—C41.461 (3)N14—C151.462 (3)
N3—C101.461 (4)N14—C211.464 (3)
C4—C51.555 (4)C15—C161.556 (3)
C4—C121.513 (4)C15—H1511.002
C4—H410.972C16—O171.416 (3)
C5—O61.420 (3)C16—C181.521 (4)
C5—C71.530 (4)C16—H1610.998
C5—H510.988O17—H1710.804
O6—H610.829C18—O191.440 (3)
C7—O81.437 (3)C18—C201.521 (4)
C7—C91.513 (4)C18—H1811.008
C7—H710.983O19—H1910.819
O8—H810.830C20—C211.525 (4)
C9—C101.523 (4)C20—O221.419 (3)
C9—O111.422 (3)C20—H2011.008
C9—H911.000C21—H2120.984
C10—H1020.958C21—H2110.996
C10—H1010.957O22—H2210.832
O1—C2—N3122.3 (3)C4—C12—O13119.8 (3)
O1—C2—C15120.5 (2)C4—C12—N14118.0 (2)
N3—C2—C15117.1 (2)O13—C12—N14122.2 (3)
C2—N3—C4122.0 (2)C12—N14—C15122.7 (2)
C2—N3—C10119.1 (2)C12—N14—C21121.4 (2)
C4—N3—C10112.9 (2)C15—N14—C21113.2 (2)
N3—C4—C5107.4 (2)C2—C15—N14114.8 (2)
N3—C4—C12113.0 (2)C2—C15—C16112.3 (2)
C5—C4—C12112.8 (2)N14—C15—C16108.0 (2)
N3—C4—H41107.4C2—C15—H151107.3
C5—C4—H41109.1N14—C15—H151108.0
C12—C4—H41106.9C16—C15—H151105.9
C4—C5—O6110.9 (2)C15—C16—O17109.7 (2)
C4—C5—C7112.0 (2)C15—C16—C18110.2 (2)
O6—C5—C7107.6 (2)O17—C16—C18107.7 (2)
C4—C5—H51106.8C15—C16—H161109.3
O6—C5—H51109.8O17—C16—H161110.5
C7—C5—H51109.7C18—C16—H161109.5
C5—O6—H61121.6C16—O17—H171121.1
C5—C7—O8108.9 (2)C16—C18—O19109.8 (2)
C5—C7—C9113.3 (2)C16—C18—C20114.6 (2)
O8—C7—C9106.9 (2)O19—C18—C20108.3 (2)
C5—C7—H71109.6C16—C18—H181108.6
O8—C7—H71108.6O19—C18—H181107.2
C9—C7—H71109.5C20—C18—H181108.0
C7—O8—H81114.0C18—O19—H191113.2
C7—C9—C10110.2 (2)C18—C20—C21109.4 (2)
C7—C9—O11107.8 (2)C18—C20—O22107.0 (2)
C10—C9—O11112.5 (2)C21—C20—O22111.5 (2)
C7—C9—H91109.0C18—C20—H201108.8
C10—C9—H91106.9C21—C20—H201108.8
O11—C9—H91110.3O22—C20—H201111.2
C9—C10—N3107.2 (2)C20—C21—N14108.9 (2)
C9—C10—H102111.1C20—C21—H212109.8
N3—C10—H102108.5N14—C21—H212110.0
C9—C10—H101109.1C20—C21—H211107.9
N3—C10—H101110.5N14—C21—H211109.3
H102—C10—H101110.3H212—C21—H211110.9
C9—O11—H111104.2C20—O22—H221118.2

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C4—H41···O11i0.972.483.455 (4)176
C15—H151···O6ii1.002.393.337 (4)157
O8—H81···O17iii0.831.952.756 (4)162
O22—H221···O1iv0.832.222.917 (4)141
O19—H191···O11v0.822.122.793 (4)139
O11—H111···O13vi0.831.862.685 (4)173
O17—H171···O8v0.801.872.633 (4)157
O6—H61···O19vii0.831.972.680 (4)143

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) x−1, y, z; (iii) x+1, y, z; (iv) x, y−1, z; (v) x−1/2, −y+3/2, −z+1; (vi) x, y+1, z; (vii) x+1/2, −y+1/2, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH5005).

References

  • Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst.27, 435.
  • Bashyal, B. P., Chow, H.-F., Fellows, L. E. & Fleet, G. W. J. (1987). Tetrahedron, 43, 415–422.
  • Bashyal, B. P., Chow, H.-F. & Fleet, G. W. J. (1986). Tetrahedron Lett.27, 3205–3208.
  • Bashyal, B. P., Chow, H.-F. & Fleet, G. W. J. (1987). Tetrahedron, 43, 423–430.
  • Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst.36, 1487.
  • Bello, I. C. di, Dorling, P., Fellows, L. & Winchester, B. (1984). FEBS Lett 176, 61–64. [PubMed]
  • Manning, K. S., Lynn, D. G., Shabanowitz, J., Fellows, L., Singh, M. & Schrire, B. D. (1985). J. Chem. Soc. Chem. Commun. pp. 127–129.
  • Nonius (2001). COLLECT Nonius BV, Delft, The Netherlands.
  • Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  • Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON Chemical Crystallography Laboratory, Oxford, UK.

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