organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

Isogentisin (1,3-di­hy­droxy-7-meth­oxy­xanthone)

CROSSMARK_Color_square_no_text.svg

aDepartment of Chemistry, University of Durham, South Road, Durham DH1 3LE, England, and bInstitute for Medicinal Plant Research, Tadeuša Košćuška 1, 11000 Belgrade, Serbia and Montenegro
*Correspondence e-mail: ivana.radosavljevic@durham.ac.uk

(Received 3 August 2004; accepted 10 August 2004; online 21 August 2004)

The crystal structure of isogentisin, C14H10O5, a natural product isolated from Gentiana lutea, has been determined. The phenolic ring system is essentially planar and the displacement of the methoxy substituent from the mean molecular plane is very small. The structure is stabilized by a one-dimensional chain of intermolecular hydrogen bonds.

Comment

Xanthone compounds commonly occur in several higher plant families, such as Gentianaceae, Guttiferae, Moraceae and Polygalaceae. The study of xanthones is interesting both from the chemosystematic and pharmacological point of view. Inhibition of Type A and Type B mono­amine oxidases (MAO) by a number of xanthones has been observed (Suzuki et al., 1980[Suzuki, O., Katsumata, Y., Oya, M., Chari, V. M., Klapfenberger, R., Wagner, H. & Hostettmann, K. (1980). Planta Med. 39, 19-23.], 1981[Suzuki, O., Katsumata, Y., Oya, M., Chari, V. M., Vermes, B., Wagner, H. & Hostettmann, K. (1981). Planta Med. 42, 17-21.]). Among the xanthones that have been tested, isogentisin revealed potent MAO inhibition (Suzuki et al., 1978[Suzuki, O., Katsumata, Y., Oya, M., Chari, V. M., Klapfenberger, R., Wagner, H. & Hostettmann, K. (1978). Biochem. Pharm. 27, 2075-2078.]). Four ethano­lic extracts prepared from leaves, flowers and roots of Gentiana lutea were tested for antitubercular activity against Mycobacterium bovis (BCG-strain). The extract obtained from flowers showed strong inhibition at a concentration of 1000 µg ml−1 and slight inhibition at 500 µg ml−1. This activity increased during the various purification steps, which finally led to the isolation of the active compound isogentisin (Menković et al., 1999[Menković, N., Savikin-Fodulović, K. & Cebedzić, R. (1999). Pharm. Pharmacol. Lett. 9, 74-75.]). Mutagenicity in the Ames test in Salmonella typhimurium was also shown for isogentisin (Morimoto et al., 1983[Morimoto, I., Nozaka, T., Watanabe, F., Ishino, M., Hirose, Y. & Okitsu, T. (1983). Mutation Res. 116, 103-117.], Matsushima et al., 1985[Matsushima, T., Araki, A., Yagame, O., Muramatsu, M., Koyama, K., Ohsawa, K., Natori, S. & Tomimori, H. (1985). Mutation Res. 150, 141-146.]). Isogentisin was first isolated by Cannonica & Pelizzoni (1955[Cannonica, L. & Pelizzoni, F. (1955). Gazzetta, 85, 1007-1024.]). The present paper presents the first single-crystal X-ray analysis of isogentisin and confirms that the crystal structure correpsonds to 1,3-di­hydroxy-7-methoxy­xanthone, (I) (Fig. 1[link]). The 1,3-di­hydroxy-7-methoxy­xanthone fragment is essentially planar, with the largest displacement within the phenolic ring system of 0.062 (3) Å for C1. The methyl group of the methoxy substituent lies close to the mean plane of the mol­ecule, as shown by the torsion angle of C10—C9—O15—C19 of 5.2 (5)°.[link]

[Scheme 1]

The packing diagram for isogentisin is shown in Figs. 2[link] and 3[link]. The crystal structure can be described in terms of parallel mol­ecules stacked along the direction of the a crystallographic axis, with the normal to the plane forming an angle of about 20° relative to it, and an intermolecular separation of about 3.5 Å. Within a xanthone unit, an intramolecular hydrogen bond with a length of 1.91 Å exists between the hydroxyl H atom H7 and the O5 acceptor of an adjacent carbonyl group. In addition, the same carbonyl O atom participates in a one-dimensional intermolecular hydrogen bond with the hydroxyl group on a neighbouring mol­ecule (O5—H5 = 1.997 Å). The hydrogen-bonding patterns are shown in Fig. 4[link].

[Figure 1]
Figure 1
The molecular structure of isogentisin and the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
Figure 2
One view of the packing diagram for isogentisin.
[Figure 3]
Figure 3
A second view of the packing diagram for isogentisin.
[Figure 4]
Figure 4
Hydro­gen bonding in isogentisin.

Experimental

Isolation of isogentisin from Gentiana lutea was carried out following a procedure described previously (Menković, 1997[Menković, N. (1997). PhD thesis, University of Belgrade, Serbia and Montenegro.]; Menković et al., 1990[Menković, N., Savikin-Fodulović, K. & Cebedzić, R. (1999). Pharm. Pharmacol. Lett. 9, 74-75.]).

Crystal data
  • C14H10O5

  • Mr = 258.23

  • Triclinic, [P\overline 1]

  • a = 7.2287 (14) Å

  • b = 8.6286 (15) Å

  • c = 9.0370 (16) Å

  • α = 97.896 (5)°

  • β = 105.962 (6)°

  • γ = 97.698 (5)°

  • V = 528.00 (17) Å3

  • Z = 2

  • Dx = 1.611 Mg m−3

  • Mo Kα radiation

  • Cell parameters from 826 reflections

  • θ = 6.0–49.1°

  • μ = 0.12 mm−1

  • T = 120 K

  • Needle, yellow

  • 0.08 × 0.04 × 0.02 mm

Data collection
  • Bruker SMART 6000 diffractometer

  • ω scans

  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996[Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.]) Tmin = 0.956, Tmax = 1.000

  • 4830 measured reflections

  • 1866 independent reflections

  • 783 reflections with I > 2σ(I)

  • Rint = 0.01

  • θmax = 25.0°

  • h = −8 → 8

  • k = −10 → 10

  • l = −10 → 10

Refinement
  • Refinement on F2

  • R[F2 > 2σ(F2)] = 0.034

  • wR(F2) = 0.117

  • S = 0.96

  • 1858 reflections

  • 172 parameters

  • H-atom parameters constrained

  • Weighting scheme: see text

  • (Δ/σ)max = 0.001

  • Δρmax = 0.69 e Å−3

  • Δρmin = −0.59 e Å−3

Table 1
Selected geometric parameters (Å, °)

C1—C13 1.392 (4)
C1—C17 1.369 (4)
C2—C11 1.441 (4)
C2—C12 1.401 (4)
C2—C17 1.425 (4)
C3—C4 1.387 (4)
C3—C10 1.404 (4)
C3—C11 1.454 (4)
C4—O8 1.373 (4)
C4—C18 1.401 (4)
O5—C11 1.256 (4)
O6—C13 1.352 (4)
O7—C17 1.349 (4)
O8—C12 1.364 (3)
C9—C10 1.376 (4)
C9—C14 1.400 (5)
C9—O15 1.362 (4)
C12—C16 1.376 (4)
C13—C16 1.390 (4)
C14—C18 1.372 (4)
O15—C19 1.422 (4)
C13—C1—C17 119.9 (3)
C11—C2—C12 120.8 (3)
C11—C2—C17 122.4 (3)
C12—C2—C17 116.8 (3)
C4—C3—C10 118.7 (3)
C4—C3—C11 119.7 (3)
C10—C3—C11 121.6 (3)
C3—C4—O8 122.8 (3)
C3—C4—C18 121.4 (3)
O8—C4—C18 115.8 (3)
C4—O8—C12 119.4 (2)
C10—C9—C14 120.6 (3)
C10—C9—O15 125.2 (3)
C14—C9—O15 114.2 (3)
C3—C10—C9 120.0 (3)
C3—C11—C2 115.8 (3)
C3—C11—O5 122.0 (3)
C2—C11—O5 122.2 (3)
C2—C12—O8 121.5 (3)
C2—C12—C16 122.8 (3)
O8—C12—C16 115.7 (3)
C1—C13—O6 116.8 (3)
C1—C13—C16 121.1 (3)
O6—C13—C16 122.0 (3)
C9—C14—C18 120.2 (3)
C9—O15—C19 117.9 (2)
C13—C16—C12 118.4 (3)
C2—C17—C1 121.0 (3)
C2—C17—O7 120.8 (3)
C1—C17—O7 118.2 (3)
C4—C18—C14 119.1 (3)

Table 2
Hydrogen-bonding geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O6—H5⋯O5i 0.82 2.00 2.738 (3) 150
O7—H7⋯O5 0.82 1.91 2.634 (3) 147
Symmetry code: (i) x,y-1,z.

A Chebychev polynomial (Carruthers & Watkin, 1979[Carruthers, J. R. & Watkin, D. J. (1979). Acta Cryst. A35, 698-699.]; Prince, 1982[Prince, E. (1982). Mathematical Techniques in Crystallography and Materials Science. New York: Springer-Verlag.]) was used for the weighting scheme, with w = 1.0/[A0T0(x) + A1T1(x)… + An − 1]Tn − 1(x)] where Ai are the Chebychev coeff­icients listed below and x = Fcalc/Fmax; robust weighting (Prince, 1982[Prince, E. (1982). Mathematical Techniques in Crystallography and Materials Science. New York: Springer-Verlag.]): W = w[1 − (δF/6σF)2]2, Ai are 1.96, 2.45 and 0.676. H atoms were positioned geometrically (C—H = 1.0 Å and O—H = 0.82 Å) and refined using a riding model, with Uiso(H) = 1.2Ueq(C) and 1.1Ueq(O).

Data collection: SMART (Bruker, 1999[Bruker (1999). SMART (Version 5.049) and SAINT (Version 5.00). Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 1999[Bruker (1999). SMART (Version 5.049) and SAINT (Version 5.00). Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT (Bruker, 1999[Bruker (1999). SMART (Version 5.049) and SAINT (Version 5.00). Bruker AXS Inc., Madison, Wisconsin, USA.]); program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.]); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003[Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.]); mol­ecular graphics: ATOMS (Shape Software, 2000[Shape Software (2000). ATOMS. Version 5.1. Shape Software, Kingsport, TN, USA.]); software used to prepare material for publication: CRYSTALS.

Supporting information


Computing details top

Data collection: SMART (Bruker, 1999); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ATOMS (Shape Software, 2000); software used to prepare material for publication: CRYSTALS.

1,3-dihydroxy-7-methoxyxanthone top
Crystal data top
C14H10O5Z = 2
Mr = 258.23F(000) = 268
Triclinic, P1Dx = 1.611 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.2287 (14) ÅCell parameters from 826 reflections
b = 8.6286 (15) Åθ = 6.0–49.1°
c = 9.0370 (16) ŵ = 0.12 mm1
α = 97.896 (5)°T = 120 K
β = 105.962 (6)°Needle, yellow
γ = 97.698 (5)°0.08 × 0.04 × 0.02 mm
V = 528.00 (17) Å3
Data collection top
Bruker SMART 6000
diffractometer
783 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.01
ω scansθmax = 25.0°, θmin = 2.4°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 88
Tmin = 0.956, Tmax = 1.000k = 1010
4830 measured reflectionsl = 1010
1866 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.034H-atom parameters not refined
wR(F2) = 0.117 Chebychev polynomial (Carruthers, 1979; Prince, 1982) w = 1.0/[A0T0(x) + A1T1(x) ··· + An-1]Tn-1(x)]
where Ai are the Chebychev coefficients listed below and x = F /Fmax; robust weighting (Prince, 1982): W = w[1-(δF/6σF)2]2, Ai are 1.96, 2.45 and 0.676
S = 0.96(Δ/σ)max = 0.001
1858 reflectionsΔρmax = 0.69 e Å3
172 parametersΔρmin = 0.59 e Å3
0 restraints
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.9594 (4)0.1431 (4)0.6659 (4)0.0173
C21.1318 (5)0.3728 (4)0.8682 (4)0.0177
C31.3211 (4)0.5934 (3)1.0799 (3)0.0154
C41.3865 (5)0.4805 (4)1.1671 (3)0.0181
O51.1236 (3)0.6399 (3)0.8389 (2)0.0220
O60.9766 (3)0.1150 (2)0.7128 (2)0.0230
O70.9354 (3)0.3977 (3)0.6125 (3)0.0235
O81.3262 (3)0.3199 (2)1.1131 (2)0.0195
C91.5219 (5)0.7988 (4)1.2928 (4)0.0179
C101.3905 (5)0.7550 (4)1.1453 (4)0.0179
C111.1864 (5)0.5423 (4)0.9226 (4)0.0184
C121.2023 (4)0.2669 (4)0.9653 (3)0.0161
C131.0311 (5)0.0431 (4)0.7678 (4)0.0178
C141.5887 (5)0.6835 (4)1.3786 (4)0.0192
O151.6008 (3)0.9514 (2)1.3672 (2)0.0216
C161.1517 (4)0.1043 (4)0.9191 (4)0.0161
C171.0072 (4)0.3046 (4)0.7146 (4)0.0168
C181.5215 (5)0.5249 (4)1.3170 (3)0.0188
C191.5317 (5)1.0763 (4)1.2928 (4)0.0231
H51.0557 (3)0.1619 (2)0.7637 (2)0.0250*
H70.9795 (3)0.4911 (3)0.6531 (3)0.0250*
H11.6017 (5)1.1812 (4)1.3599 (4)0.0265*
H31.5570 (5)1.0684 (4)1.1889 (4)0.0265*
H21.3881 (5)1.0671 (4)1.2774 (4)0.0265*
H41.3444 (5)0.8384 (4)1.0846 (4)0.0220*
H60.8731 (4)0.0971 (4)0.5572 (4)0.0199*
H81.2004 (4)0.0320 (4)0.9927 (4)0.0200*
H101.6857 (5)0.7167 (4)1.4851 (4)0.0225*
H91.5681 (5)0.4422 (4)1.3781 (3)0.0233*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0143 (15)0.0208 (16)0.0146 (15)0.0014 (12)0.0026 (12)0.0011 (12)
C20.0178 (17)0.0183 (16)0.0186 (16)0.0025 (13)0.0082 (13)0.0038 (13)
C30.0128 (16)0.0187 (16)0.0184 (16)0.0050 (12)0.0089 (12)0.0049 (12)
C40.0201 (17)0.0165 (16)0.0173 (16)0.0003 (13)0.0078 (13)0.0011 (12)
O50.0245 (13)0.0198 (12)0.0198 (12)0.0046 (10)0.0026 (10)0.0052 (9)
O60.0278 (13)0.0152 (12)0.0220 (12)0.0035 (9)0.0016 (10)0.0025 (9)
O70.0300 (13)0.0159 (11)0.0199 (11)0.0037 (10)0.0006 (10)0.0043 (9)
O80.0236 (12)0.0165 (12)0.0159 (11)0.0014 (9)0.0030 (9)0.0024 (9)
C90.0158 (16)0.0195 (16)0.0174 (15)0.0004 (13)0.0070 (13)0.0008 (12)
C100.0166 (16)0.0177 (16)0.0208 (16)0.0040 (12)0.0071 (13)0.0041 (12)
C110.0184 (16)0.0215 (17)0.0185 (16)0.0051 (13)0.0088 (13)0.0064 (13)
C120.0145 (16)0.0202 (16)0.0157 (16)0.0032 (12)0.0076 (13)0.0038 (12)
C130.0200 (17)0.0145 (15)0.0189 (16)0.0013 (13)0.0074 (13)0.0012 (12)
C140.0172 (16)0.0237 (17)0.0153 (15)0.0029 (13)0.0042 (13)0.0007 (12)
O150.0246 (13)0.0154 (11)0.0195 (12)0.0037 (9)0.0001 (10)0.0012 (9)
C160.0132 (15)0.0171 (15)0.0195 (15)0.0030 (12)0.0063 (13)0.0048 (12)
C170.0154 (15)0.0212 (17)0.0172 (15)0.0065 (13)0.0075 (12)0.0064 (12)
C180.0216 (17)0.0217 (16)0.0148 (15)0.0042 (13)0.0063 (13)0.0074 (12)
C190.0252 (17)0.0146 (16)0.0266 (18)0.0049 (13)0.0028 (14)0.0033 (13)
Geometric parameters (Å, º) top
C1—C131.392 (4)O8—C121.364 (3)
C1—C171.369 (4)C9—C101.376 (4)
C1—H61.000C9—C141.400 (5)
C2—C111.441 (4)C9—O151.362 (4)
C2—C121.401 (4)C10—H41.000
C2—C171.425 (4)C12—C161.376 (4)
C3—C41.387 (4)C13—C161.390 (4)
C3—C101.404 (4)C14—C181.372 (4)
C3—C111.454 (4)C14—H101.000
C4—O81.373 (4)O15—C191.422 (4)
C4—C181.401 (4)C16—H81.000
O5—C111.256 (4)C18—H91.000
O6—C131.352 (4)C19—H11.000
O6—H50.819C19—H31.000
O7—C171.349 (4)C19—H21.000
O7—H70.820
C13—C1—C17119.9 (3)C2—C12—C16122.8 (3)
C13—C1—H6120.0O8—C12—C16115.7 (3)
C17—C1—H6120.0C1—C13—O6116.8 (3)
C11—C2—C12120.8 (3)C1—C13—C16121.1 (3)
C11—C2—C17122.4 (3)O6—C13—C16122.0 (3)
C12—C2—C17116.8 (3)C9—C14—C18120.2 (3)
C4—C3—C10118.7 (3)C9—C14—H10119.8
C4—C3—C11119.7 (3)C18—C14—H10119.8
C10—C3—C11121.6 (3)C9—O15—C19117.9 (2)
C3—C4—O8122.8 (3)C13—C16—C12118.4 (3)
C3—C4—C18121.4 (3)C13—C16—H8120.8
O8—C4—C18115.8 (3)C12—C16—H8120.8
C13—O6—H5109.4C2—C17—C1121.0 (3)
C17—O7—H7109.0C2—C17—O7120.8 (3)
C4—O8—C12119.4 (2)C1—C17—O7118.2 (3)
C10—C9—C14120.6 (3)C4—C18—C14119.1 (3)
C10—C9—O15125.2 (3)C4—C18—H9120.4
C14—C9—O15114.2 (3)C14—C18—H9120.4
C3—C10—C9120.0 (3)O15—C19—H1109.4
C3—C10—H4120.0O15—C19—H3109.4
C9—C10—H4120.0H1—C19—H3109.4
C3—C11—C2115.8 (3)O15—C19—H2109.4
C3—C11—O5122.0 (3)H1—C19—H2109.4
C2—C11—O5122.2 (3)H3—C19—H2109.4
C2—C12—O8121.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O6—H5···O5i0.822.002.738 (3)150
O7—H7···O50.821.912.634 (3)147
Symmetry code: (i) x, y1, z.
 

References

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