supplementary materials


rk2401 scheme

Acta Cryst. (2013). E69, o1096    [ doi:10.1107/S1600536813014451 ]

5,6-Dihydroxy-7,8-dimethoxyflavone

L.-L. Jing, X.-F. Fan, P.-C. Fan, L. He and Z.-P. Jia

Abstract top

The title compound (systematic name: 5,6-dihydroxy-7,8-dimethoxy-2-phenylchromen-4-one), C17H14O6, is a flavone that was isolated from the petroleum ether-soluble fraction of the rare traditional Chinese medicinal herb Saussurea involucrata. The flavone molecule is almost planar, with a dihedral angle between the planes of the benzopyran-4-one group and the attached phenyl group of 1.89 (6)°. The 5-hydroxy group forms a strong intramolecular hydrogen bond with the carbonyl group, resulting in a six-membered hydrogen-bonded ring. The 6-hydroxy group also forms an intramolecular O-H...O contact. In the crystal, the molecules are linked by O-H...O and C-H...O hydrogen bonds and [pi]-[pi] interactions [3.37 (2)-3.39 (2) Å], which build up a three-dimensional network.

Comment top

Saussurea involucrata (Kar. et Kir) Sch.–Bip is one of the precious Tibetan herbs that have been used for a long period of time. Modern pharmacological studies have reported that the herb exhibit a wide range of bioactivitie, including antioxidation, anti–inflammatory, anti–fatigue, anti–hypoxia, anti–cancer and analgesic effects. (Zheng et al., 1993; Gao et al., 2005; Tao et al., 2010; Ma et al., 2011; Jia et al., 2005; Liu et al., 1985; Paula et al., 2002).

Our chemical investigation of this herbs for components with anti–hypoxia activity resulted in the isolation of the title compound and crystal growth one, suitable for X–ray diffraction.

The molecular structure of title compound is almost planar; the dihedral angle between the benzopyran–4–one group and the attached phenyl group is 1.89 (6)° (Fig. 1).

In the crystal,the 5–hydroxy group forms a strong intramolecular hydrogen bond with the carbonyl group, resulting in a six–membered ring (Fig. 1). The centrosymmetrical dimers of title compound is linked by intermolecular O4—H4···O3i hydrogen bonds. Non–classical C—H···O hydrogen bonds (C2—H2···O2ii, C15—H15···O2ii and C14—H14···O4iii) and ππ interactions between molecule pairs (C3–C4–C5···C5i–C4i–C3i = 3.37 (2)–3.39 (2)Å are found in the crystal structure. All of these interactions build up a three–dimensional network. Symmetry codes: (i) -x, -y+1, -z; (ii) 1-x, -y, -z; (iii) 1+x, 1+y, z.

Related literature top

For biological activity of Saussurea involucrata, see: Zheng et al. (1993); Gao et al. (2005); Tao et al.(2010); Ma et al. (2011); Jia et al. (2005); Liu et al. (1985). For related structures, see: Xiong et al. (2009); Vijayalakshmi et al. (1986); Paula et al. (2002).

Experimental top

The air–dried whole plants (10 kg) of S. involucrate were milled and extracted with 70% ethanol (150 L×3) for 2 h each time at 351 K. The resulting extract was concentrated to give ethanol extract (2.4 kg). The ethanol extract was suspended in water and extracted successively with equal volumes petroleum ether, EtOAc and nBuOH. The petroleum ether extract (1.2 kg) was subjected to a silica gel column eluted with petroleum ether–EtOAc (10:0 to 1:2, v/v) to afford five fractions. Fraction 5 was purified repeatedly over a Sephadex LH–20 column with a mixture of CHCl3MeOH (1:1, v/v) to give title compound (500 mg). Single crystals suitable for X–ray diffraction analysis were obtained by slow evaporation from MeOH at room temperature.

1H–NMR (600 MHz, DMSd6), δ (p.p.m.): 5.53 (1H, s, –OH), 12.27 (1H, s, –OH), 7.94 (2H, m), 7.57 (3H, m), 6.70 (1H, s), 4.16 (3H, s), 4.12 (3H, s). 13C–NMR (100 MHz, DMSd6), δ (p.p.m.): 183.0, 164.2, 146.8, 143.1, 142.1, 133.3, 133.1, 132.0, 131.4, 129.1, 126.3, 106.8, 105.1, 62.2, 61.5.

Refinement top

In the structure the H atoms were positioned geometrically and refined with using a riding model: C—H = 0.96Å for methyl H; C—H = 0.97Å for methylene H and C—H = 0.93Å for aryl H with Uiso(H) = 1.5Ueq(C) for methyl H and Uiso(H) = 1.2Ueq(C) for other. Hydroxy H atoms were positioned with O—H = 0.82Å and Uiso(H) = 1.5Ueq(O).

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are presented as a small spheres of arbitrary radius. Hydrogen bond is shown as dashed lines.
5,6-dihydroxy-7,8-dimethoxy-2-phenylchromen-4-one top
Crystal data top
C17H14O6Z = 2
Mr = 314.28F(000) = 328
Triclinic, P1Dx = 1.437 Mg m3
a = 7.953 (6) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.548 (6) ÅCell parameters from 1607 reflections
c = 10.951 (8) Åθ = 2.4–28.0°
α = 96.602 (8)°µ = 0.11 mm1
β = 92.282 (8)°T = 295 K
γ = 100.279 (7)°Block, orange
V = 726.3 (9) Å30.21 × 0.16 × 0.09 mm
Data collection top
Bruker APEXII CCD
diffractometer
1786 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.036
Graphite monochromatorθmax = 28.3°, θmin = 2.4°
φ and ω scansh = 910
5252 measured reflectionsk = 1011
3368 independent reflectionsl = 1414
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.070Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.236H-atom parameters constrained
S = 1.03 w = 1/[σ2(Fo2) + (0.1286P)2]
where P = (Fo2 + 2Fc2)/3
3368 reflections(Δ/σ)max < 0.001
212 parametersΔρmax = 0.32 e Å3
0 restraintsΔρmin = 0.32 e Å3
Crystal data top
C17H14O6γ = 100.279 (7)°
Mr = 314.28V = 726.3 (9) Å3
Triclinic, P1Z = 2
a = 7.953 (6) ÅMo Kα radiation
b = 8.548 (6) ŵ = 0.11 mm1
c = 10.951 (8) ÅT = 295 K
α = 96.602 (8)°0.21 × 0.16 × 0.09 mm
β = 92.282 (8)°
Data collection top
Bruker APEXII CCD
diffractometer
1786 reflections with I > 2σ(I)
5252 measured reflectionsRint = 0.036
3368 independent reflectionsθmax = 28.3°
Refinement top
R[F2 > 2σ(F2)] = 0.070H-atom parameters constrained
wR(F2) = 0.236Δρmax = 0.32 e Å3
S = 1.03Δρmin = 0.32 e Å3
3368 reflectionsAbsolute structure: ?
212 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.6956 (2)0.4357 (2)0.24860 (16)0.0386 (5)
O20.3542 (3)0.1892 (2)0.02333 (18)0.0489 (6)
O30.1717 (2)0.4078 (2)0.00746 (18)0.0450 (5)
H30.19470.32120.01960.067*
O40.1217 (3)0.6852 (2)0.14665 (19)0.0512 (6)
H40.05940.62910.09090.077*
O50.3574 (3)0.8349 (2)0.32644 (18)0.0528 (6)
O60.6457 (2)0.7095 (2)0.38048 (16)0.0450 (5)
C10.7247 (3)0.2981 (3)0.1857 (2)0.0354 (6)
C20.6135 (4)0.2132 (3)0.0965 (3)0.0405 (7)
H20.63680.11750.05760.049*
C30.4604 (3)0.2653 (3)0.0593 (2)0.0359 (6)
C40.4325 (3)0.4143 (3)0.1259 (2)0.0303 (6)
C50.2887 (3)0.4797 (3)0.1000 (2)0.0334 (6)
C60.2615 (3)0.6188 (3)0.1678 (2)0.0367 (6)
C70.3817 (4)0.6939 (3)0.2618 (2)0.0377 (7)
C80.5273 (3)0.6333 (3)0.2885 (2)0.0360 (6)
C90.5500 (3)0.4924 (3)0.2197 (2)0.0338 (6)
C100.8873 (3)0.2593 (3)0.2294 (2)0.0362 (6)
C110.9879 (4)0.3551 (4)0.3266 (3)0.0457 (7)
H110.95240.44610.36370.055*
C121.1388 (4)0.3168 (4)0.3683 (3)0.0555 (9)
H121.20370.38090.43400.067*
C131.1942 (4)0.1838 (4)0.3130 (3)0.0558 (9)
H131.29690.15840.34070.067*
C141.0974 (4)0.0895 (4)0.2172 (3)0.0569 (9)
H141.13420.00100.18050.068*
C150.9459 (4)0.1264 (4)0.1742 (3)0.0492 (8)
H150.88260.06200.10790.059*
C160.2964 (6)0.8185 (5)0.4437 (4)0.0927 (14)
H16A0.18330.75470.43530.139*
H16B0.29290.92240.48620.139*
H16C0.37120.76710.48970.139*
C170.7790 (5)0.8185 (4)0.3370 (3)0.0655 (10)
H17A0.83860.76150.27740.098*
H17B0.85750.86940.40480.098*
H17C0.73130.89820.29950.098*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0383 (11)0.0392 (11)0.0415 (10)0.0216 (9)0.0029 (8)0.0015 (8)
O20.0437 (12)0.0463 (12)0.0544 (12)0.0171 (9)0.0080 (9)0.0127 (9)
O30.0383 (12)0.0452 (12)0.0511 (12)0.0182 (9)0.0083 (9)0.0080 (9)
O40.0429 (13)0.0525 (13)0.0612 (14)0.0296 (10)0.0074 (10)0.0096 (10)
O50.0668 (15)0.0453 (12)0.0497 (12)0.0305 (11)0.0005 (10)0.0101 (9)
O60.0451 (12)0.0519 (12)0.0370 (11)0.0143 (10)0.0040 (9)0.0044 (9)
C10.0384 (16)0.0329 (14)0.0393 (15)0.0161 (12)0.0063 (12)0.0063 (11)
C20.0404 (17)0.0367 (15)0.0476 (16)0.0201 (13)0.0026 (13)0.0020 (12)
C30.0344 (15)0.0381 (15)0.0365 (14)0.0121 (12)0.0019 (11)0.0009 (11)
C40.0321 (14)0.0321 (14)0.0290 (13)0.0118 (11)0.0047 (10)0.0031 (10)
C50.0310 (15)0.0388 (15)0.0315 (13)0.0112 (12)0.0005 (11)0.0027 (10)
C60.0340 (15)0.0395 (15)0.0406 (15)0.0186 (12)0.0018 (11)0.0035 (11)
C70.0423 (17)0.0371 (15)0.0376 (14)0.0198 (13)0.0069 (12)0.0001 (11)
C80.0402 (16)0.0409 (15)0.0277 (13)0.0140 (12)0.0011 (11)0.0017 (10)
C90.0320 (15)0.0403 (15)0.0329 (14)0.0166 (12)0.0016 (11)0.0052 (11)
C100.0338 (15)0.0364 (15)0.0433 (15)0.0141 (12)0.0069 (12)0.0121 (11)
C110.0458 (18)0.0488 (18)0.0464 (16)0.0202 (14)0.0006 (13)0.0051 (13)
C120.046 (2)0.068 (2)0.0549 (19)0.0154 (17)0.0082 (15)0.0124 (16)
C130.0407 (19)0.065 (2)0.071 (2)0.0237 (17)0.0030 (16)0.0252 (18)
C140.048 (2)0.0475 (19)0.082 (2)0.0252 (16)0.0080 (17)0.0113 (17)
C150.0446 (18)0.0439 (17)0.0628 (19)0.0200 (14)0.0016 (14)0.0043 (14)
C160.134 (4)0.090 (3)0.066 (2)0.055 (3)0.041 (2)0.006 (2)
C170.064 (2)0.063 (2)0.060 (2)0.0004 (18)0.0005 (17)0.0104 (16)
Geometric parameters (Å, º) top
O1—C11.355 (3)C7—C81.384 (4)
O1—C91.372 (3)C8—C91.389 (4)
O2—C31.250 (3)C10—C111.393 (4)
O3—H30.8200C10—C151.388 (4)
O3—C51.360 (3)C11—H110.9300
O4—H40.8200C11—C121.374 (4)
O4—C61.359 (3)C12—H120.9300
O5—C71.375 (3)C12—C131.377 (5)
O5—C161.404 (4)C13—H130.9300
O6—C81.372 (3)C13—C141.365 (4)
O6—C171.417 (4)C14—H140.9300
C1—C21.343 (4)C14—C151.378 (4)
C1—C101.467 (4)C15—H150.9300
C2—H20.9300C16—H16A0.9600
C2—C31.429 (4)C16—H16B0.9600
C3—C41.450 (4)C16—H16C0.9600
C4—C51.393 (4)C17—H17A0.9600
C4—C91.385 (4)C17—H17B0.9600
C5—C61.384 (4)C17—H17C0.9600
C6—C71.391 (4)
C1—O1—C9119.6 (2)C4—C9—C8121.7 (2)
C5—O3—H3109.5C11—C10—C1121.1 (2)
C6—O4—H4109.5C15—C10—C1120.8 (3)
C7—O5—C16114.1 (3)C15—C10—C11118.1 (3)
C8—O6—C17112.7 (2)C10—C11—H11119.6
O1—C1—C10111.1 (2)C12—C11—C10120.8 (3)
C2—C1—O1121.9 (2)C12—C11—H11119.6
C2—C1—C10127.0 (2)C11—C12—H12119.9
C1—C2—H2119.0C11—C12—C13120.2 (3)
C1—C2—C3122.1 (2)C13—C12—H12119.9
C3—C2—H2119.0C12—C13—H13120.2
O2—C3—C2123.7 (2)C14—C13—C12119.5 (3)
O2—C3—C4120.9 (2)C14—C13—H13120.2
C2—C3—C4115.4 (2)C13—C14—H14119.5
C5—C4—C3121.9 (2)C13—C14—C15121.0 (3)
C9—C4—C3119.3 (2)C15—C14—H14119.5
C9—C4—C5118.8 (2)C10—C15—H15119.8
O3—C5—C4120.6 (2)C14—C15—C10120.3 (3)
O3—C5—C6118.5 (2)C14—C15—H15119.8
C6—C5—C4120.9 (2)O5—C16—H16A109.5
O4—C6—C5122.7 (2)O5—C16—H16B109.5
O4—C6—C7118.5 (2)O5—C16—H16C109.5
C5—C6—C7118.8 (2)H16A—C16—H16B109.5
O5—C7—C6118.7 (2)H16A—C16—H16C109.5
O5—C7—C8119.5 (2)H16B—C16—H16C109.5
C8—C7—C6121.7 (2)O6—C17—H17A109.5
O6—C8—C7121.1 (2)O6—C17—H17B109.5
O6—C8—C9120.8 (2)O6—C17—H17C109.5
C7—C8—C9118.1 (2)H17A—C17—H17B109.5
O1—C9—C4121.7 (2)H17A—C17—H17C109.5
O1—C9—C8116.6 (2)H17B—C17—H17C109.5
O1—C1—C2—C32.1 (4)C3—C4—C9—C8178.3 (2)
O1—C1—C10—C112.1 (4)C4—C5—C6—O4179.0 (2)
O1—C1—C10—C15177.4 (3)C4—C5—C6—C70.8 (4)
O2—C3—C4—C50.7 (4)C5—C4—C9—O1179.0 (2)
O2—C3—C4—C9177.8 (2)C5—C4—C9—C80.3 (4)
O3—C5—C6—O40.9 (4)C5—C6—C7—O5177.9 (2)
O3—C5—C6—C7179.3 (2)C5—C6—C7—C80.3 (4)
O4—C6—C7—O52.3 (4)C6—C7—C8—O6179.2 (2)
O4—C6—C7—C8179.9 (3)C6—C7—C8—C91.0 (4)
O5—C7—C8—O61.6 (4)C7—C8—C9—O1180.0 (2)
O5—C7—C8—C9178.6 (2)C7—C8—C9—C40.7 (4)
O6—C8—C9—O10.2 (4)C9—O1—C1—C21.1 (4)
O6—C8—C9—C4179.5 (2)C9—O1—C1—C10179.3 (2)
C1—O1—C9—C41.3 (4)C9—C4—C5—O3179.1 (2)
C1—O1—C9—C8179.4 (2)C9—C4—C5—C61.1 (4)
C1—C2—C3—O2180.0 (3)C10—C1—C2—C3178.3 (2)
C1—C2—C3—C40.9 (4)C10—C11—C12—C131.0 (5)
C1—C10—C11—C12179.0 (3)C11—C10—C15—C141.5 (5)
C1—C10—C15—C14178.9 (3)C11—C12—C13—C140.6 (5)
C2—C1—C10—C11177.5 (3)C12—C13—C14—C150.7 (5)
C2—C1—C10—C153.0 (4)C13—C14—C15—C101.2 (5)
C2—C3—C4—C5179.9 (2)C15—C10—C11—C121.5 (5)
C2—C3—C4—C91.3 (4)C16—O5—C7—C6103.2 (4)
C3—C4—C5—O32.4 (4)C16—O5—C7—C879.2 (4)
C3—C4—C5—C6177.5 (2)C17—O6—C8—C792.6 (3)
C3—C4—C9—O12.4 (4)C17—O6—C8—C987.6 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4···O3i0.822.052.764 (4)146
C12—H12···O6ii0.932.583.234 (4)128
O3—H3···O20.821.842.564 (3)146
O4—H4···O30.822.342.767 (3)113
C11—H11···O10.932.342.675 (4)101
Symmetry codes: (i) x, y+1, z; (ii) x+2, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC17H14O6
Mr314.28
Crystal system, space groupTriclinic, P1
Temperature (K)295
a, b, c (Å)7.953 (6), 8.548 (6), 10.951 (8)
α, β, γ (°)96.602 (8), 92.282 (8), 100.279 (7)
V3)726.3 (9)
Z2
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.21 × 0.16 × 0.09
Data collection
DiffractometerBruker APEXII CCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5252, 3368, 1786
Rint0.036
(sin θ/λ)max1)0.668
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.070, 0.236, 1.03
No. of reflections3368
No. of parameters212
No. of restraints0
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.32, 0.32

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 2012), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4···O3i0.822.052.764 (4)146
C12—H12···O6ii0.932.583.234 (4)128
O3—H3···O20.821.842.564 (3)146
O4—H4···O30.822.342.767 (3)113
C11—H11···O10.932.342.675 (4)101
Symmetry codes: (i) x, y+1, z; (ii) x+2, y+1, z+1.
Acknowledgements top

We thank the Natural Science Foundation of China (grant No. 81202458) and China Postdoctoral Science Foundation (grant No. 2012M521926) for financial support.

references
References top

Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.

Gao, X., Zhang, Z. M., Xu, A. X. & Lei, X. Y. (2005). Zhongguo Yao Xue Za Zhi, 40, 1062–1065.

Jia, J. M., Wu, C. F. & Liu, W. (2005). Biol. Pharm. Bull. 9, 1612–1614.

Liu, L. S., Xiao, X. H. & Zhang, L. D. J. (1985). Lanzhou Univ. Nat. Sci., 4, 80–83.

Ma, H. P., Fan, P. C., Jing, L. L., Yao, J., He, X. Y., Yang, Y., Chen, K. M. & Jia, Z. P. (2011). J. Ethnopharmacol. 137, 1510–1515.

Paula, V. F., Barbosa, L. C. A., Errington, W., Howarth, O. W. & Cruz, M. P. (2002). J. Braz. Chem. Soc. 13, 276–280.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Tao, Y., Zhong, Z. Z., Zhi, L. Y. & Chen, H. B. (2010). J. Ethnopharmacol. 128, 405–411.

Vijayalakshmi, J., Rajan, S. S., Srinivasan, R. & Ramachandran Nair, A. G. (1986). Acta Cryst. C42, 1752–1754.

Xiong, H.-P., Wu, Z.-J., Chen, F.-T. & Chen, W.-S. (2009). Acta Cryst. E65, o3276–o3277.

Zheng, R. L., Liu, G. S., Xing, G. X., Jia, Z. J., Du, M. & Tan, L. Q. (1993). Acta Pharmacol. Sin. 14, S47–S49.