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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1867–o1868.
Published online 2009 July 15. doi:  10.1107/S1600536809026701
PMCID: PMC2977309

Cynaratriol, a sesquiterpene lactone from Centaurea musimomum

Abstract

The title compound [systematic name: 3,8-dihydr­oxy-3-(hydroxy­meth­yl)-9-methyl-6-methyl­enedeca­hydro­azuleno[4,5-b]furan-2(3H)-one], C15H22O5, is a sesquiterpene lactone showing the typical tricyclic guaianolide skeleton which has been isolated, together with other related metabolites, from the plant Centaurea musimomum. The present study confirms the mol­ecular structure, assigned by 1H NMR and MS spectroscopy, as well as the the 11β-hydroxy­methyl, 3β-hydr­oxy and 4α-methyl stereochemistry. The crystal structure is built through a network of O—H(...)O hydrogen bonds involving the three hydroxyl groups that are present in the mol­ecular skeleton.

Related literature

For the ethyl acetate soluble extract of Centaurea musimomum, an endemic specie from Algeria, see: Quezel & Santa (1963 [triangle]). For the structures of several guaianolide type sesquiterpene lactones isolated from the chloro­form-soluble part of Centaurea musimomum, see: Medjroubi et al. (1997 [triangle], 2003 [triangle], 2005 [triangle]); González-Platas et al. (1999 [triangle]). Cynaratriol was previously isolated from Cynara species, see: von Heinz et al. (1979 [triangle]). For related structures, see: Oksuz et al. (1993 [triangle]); González-Platas et al. (1999 [triangle]).

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Object name is e-65-o1867-scheme1.jpg

Experimental

Crystal data

  • C15H22O5
  • M r = 282.33
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1867-efi1.jpg
  • a = 8.417 (4) Å
  • b = 9.919 (3) Å
  • c = 17.187 (8) Å
  • V = 1434.9 (10) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 K
  • 0.40 × 0.30 × 0.25 mm

Data collection

  • Nonius KappaCCD diffractometer
  • Absorption correction: none
  • 8829 measured reflections
  • 2054 independent reflections
  • 1847 reflections with I > 2σ(I)
  • R int = 0.038

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.101
  • S = 1.11
  • 2054 reflections
  • 194 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.17 e Å−3

Data collection: COLLECT (Nonius, 2000 [triangle]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 [triangle]); data reduction: SCALEPACK and DENZO (Otwinowski & Minor, 1997 [triangle]); program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809026701/bx2222sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809026701/bx2222Isup2.hkl

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

Acknowledgments

The authors wish to thank Professor N. Khalfallah of the Nature and Life Sciences Department, Mentorui University of Constantine, Algerie, for the identification of the plant material.

supplementary crystallographic information

Comment

The Centaurea genus plants are a natural source of various type of sesquiterpenic lactones, many of which have been shown to be biologically active: Medjroubi, Benayache & Bermejo. In connection with a systematic study of this genus, we have investigated the ethyl acetate soluble extract of Centaurea musimomum, an endemic specie from Algeria: Quezel & Santa, (1963). Our previous phytochemical study of the chloroform soluble part led to the isolation an molecular structure determination of several guaianolide type sesquiterpene lactones: Medjroubi et al., 1997; González-Platas et al. 1999; Medjroubi et al., 2003. Cynaratriol was previously isolated from Cynara species (Heinz, Thiele & Pretsch, 1979). In this work we report the isolation and the molecular and crystal structure determination of the title compound, which it is described for the first time as a metabolite for the Centaurea genus. The lack of suitable anomalous scatters did not allow us to reliably determine the absolute structure and that shown was chosen to be the same as that the, close related, 4β,15-Dihydro-3-dehydrosolstiatilin A (González-Platas et al., 1999) and its acetate (Oksuz, Clark & Herz, 1993).

Refinement

The H-atoms of the hydroxyl groups were located on difference-Fourier map and freely refined. All other H atoms were positioned with idealized geometry: C—H = 0.98(CH3), 0.99(CH2), 1.00(CH) Å and included in the refinement in a riding-model approximation with Uiso(H) = 1.2Ueq(C) and Uiso(H) = 1.5Ueq for methyl. The lack of suitable anomalous scatters did not allow us to reliably determine the absolute structure according to the Flack parameters: -10 (10) and, therefore, the Friedel pairs were merged prior to the final refinement.

Figures

Fig. 1.
Molecular structure of cynaratriol represented showing displacement ellipsoids at the 50% probability level.
Fig. 2.
A view of the hydrogen-bonding network. Hydrogen atoms not involved in the O—H···O interactions have been omitted.

Crystal data

C15H22O5F(000) = 608
Mr = 282.33Dx = 1.307 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 7053 reflections
a = 8.417 (4) Åθ = 3.2–28.6°
b = 9.919 (3) ŵ = 0.10 mm1
c = 17.187 (8) ÅT = 293 K
V = 1434.9 (10) Å3Block, colourless
Z = 40.40 × 0.30 × 0.25 mm

Data collection

Enraf–Nonius KappaCCD diffractometer1847 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.038
graphiteθmax = 28.6°, θmin = 3.2°
Detector resolution: 9 pixels mm-1h = −10→11
[var phi] and ω scansk = −12→12
8829 measured reflectionsl = −22→23
2054 independent reflections

Refinement

Refinement on F20 restraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.042w = 1/[σ2(Fo2) + (0.0447P)2 + 0.2149P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.101(Δ/σ)max = 0.01
S = 1.11Δρmax = 0.21 e Å3
2054 reflectionsΔρmin = −0.17 e Å3
194 parameters

Special details

Experimental. Centaurea musimomum L.was collected in June 2002 in Didouche Mourad (Constantine) Algeria and authenticated by Professor Nadra Khalfallah (Quezel & Santa, 1963). A voucher specimen was deposited in the herbarium of the Department of Nature and Life Sciences, Mentouri University, Constantine. Air-dried leaves (339 g) and air-dried flowers (202 g) were separately macerated, three times for 24 h, at room temperature with a mixture of methanol-water (70:30). The filtrates were concentrated and successsively extracted with petrol, chloroform, ethyl acetate and n-butanol. The ethyl acetate phases yield, after drying and solvent evaporation 10.8 g and 4.9 g respectively. Analysis by TLC on silica-gel plates showed no significant differences between the leaves and the flowers extract and they were mixed. A part (13 g) of the combined extract was chromatographed on a 230–400 mesh silica gel (325 g) column with chloroform-acetone mixtures of increasing polarity as elution solvents to yield the title compound: cynaratriol together with other related sesquiterpene lactones.The molecular formula C~15~ H~22~ O~5~ was deduced from its high resolution MS spectrum which shows a molecular ion at m/z=280.1329. The ^13Ĉ and ^1ĤNMR data are very similar to those of 4β,15-Dihydro-3-dehydrosolstiatilin A (Medjroubi et al., 2003), the differences arises from the replacement of the oxo group at C3 by an hydroxyl group.
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 > 2σ(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)

xyzUiso*/Ueq
O1−0.0496 (3)0.33998 (17)0.44392 (9)0.0577 (5)
H1O−0.107 (5)0.379 (4)0.469 (2)0.108 (15)*
O2−0.14872 (16)0.42543 (15)0.15121 (8)0.0379 (3)
O3−0.30157 (18)0.45503 (19)0.04747 (9)0.0540 (4)
O4−0.0339 (3)0.60068 (15)−0.01439 (9)0.0521 (5)
H4O−0.020 (4)0.673 (3)0.0102 (18)0.070 (9)*
O50.0257 (3)0.25259 (15)0.02916 (9)0.0536 (5)
H5O0.074 (3)0.190 (3)0.0041 (15)0.052 (7)*
C10.2066 (2)0.4743 (2)0.28881 (12)0.0388 (5)
H10.23760.56130.31120.047*
C20.1768 (3)0.3797 (2)0.35773 (12)0.0472 (5)
H2A0.17270.28630.34120.057*
H2B0.2580.38980.39730.057*
C30.0174 (3)0.4275 (2)0.38653 (11)0.0422 (5)
H30.02920.51790.40880.051*
C4−0.0815 (2)0.4369 (2)0.31246 (11)0.0358 (4)
H4−0.10960.34530.29620.043*
C50.0359 (2)0.49556 (18)0.25231 (10)0.0308 (4)
H50.01630.59260.24780.037*
C60.0215 (2)0.43313 (19)0.17180 (10)0.0289 (4)
H60.06750.34240.17210.035*
C70.0949 (2)0.51598 (19)0.10596 (10)0.0326 (4)
H70.08130.61110.120.039*
C80.2719 (3)0.4939 (3)0.09333 (13)0.0476 (5)
H8A0.30760.54930.05020.057*
H8B0.29060.40030.07980.057*
C90.3682 (3)0.5293 (3)0.16608 (14)0.0542 (6)
H9A0.48040.52680.15330.065*
H9B0.34250.62060.18190.065*
C100.3375 (2)0.4353 (2)0.23343 (13)0.0461 (5)
C11−0.0147 (2)0.48927 (19)0.03617 (10)0.0346 (4)
C12−0.1702 (2)0.4552 (2)0.07626 (11)0.0373 (4)
C130.0313 (3)0.37152 (19)−0.01605 (12)0.0422 (5)
H13A−0.0420.3648−0.05940.051*
H13B0.13750.3848−0.03660.051*
C140.4258 (3)0.3269 (3)0.24326 (18)0.0706 (8)
H14A0.40850.27090.28580.085*
H14B0.50550.30650.20770.085*
C15−0.2339 (3)0.5172 (3)0.32204 (14)0.0529 (6)
H15B−0.20880.60690.33910.079*
H15A−0.30050.47420.360.079*
H15C−0.28870.52130.27310.079*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0988 (15)0.0417 (8)0.0325 (8)0.0184 (9)0.0167 (9)0.0085 (6)
O20.0299 (6)0.0527 (8)0.0313 (7)−0.0041 (6)−0.0031 (6)−0.0017 (6)
O30.0408 (8)0.0734 (11)0.0476 (9)0.0025 (8)−0.0155 (7)−0.0084 (8)
O40.0908 (13)0.0333 (7)0.0323 (8)−0.0003 (8)−0.0162 (9)0.0022 (6)
O50.0823 (13)0.0323 (7)0.0462 (9)0.0082 (8)0.0134 (9)−0.0018 (7)
C10.0402 (10)0.0410 (10)0.0353 (10)−0.0029 (8)−0.0124 (8)−0.0052 (8)
C20.0600 (13)0.0485 (11)0.0330 (11)0.0082 (11)−0.0148 (10)−0.0014 (9)
C30.0679 (14)0.0321 (9)0.0268 (9)0.0063 (10)−0.0025 (10)−0.0004 (7)
C40.0454 (10)0.0334 (9)0.0286 (9)−0.0013 (9)0.0015 (8)0.0000 (7)
C50.0344 (9)0.0299 (8)0.0280 (8)0.0005 (7)−0.0039 (7)−0.0003 (7)
C60.0264 (8)0.0318 (8)0.0286 (9)0.0000 (7)−0.0024 (7)−0.0003 (7)
C70.0358 (9)0.0345 (9)0.0276 (9)−0.0040 (8)−0.0006 (8)−0.0009 (7)
C80.0375 (11)0.0649 (14)0.0403 (11)−0.0067 (11)0.0058 (9)−0.0016 (11)
C90.0317 (10)0.0745 (16)0.0563 (14)−0.0137 (11)0.0001 (10)−0.0048 (12)
C100.0295 (9)0.0611 (12)0.0476 (12)−0.0039 (10)−0.0109 (9)−0.0071 (10)
C110.0464 (10)0.0300 (8)0.0272 (9)0.0007 (8)−0.0045 (8)−0.0004 (7)
C120.0395 (10)0.0387 (10)0.0338 (10)0.0014 (9)−0.0068 (8)−0.0092 (8)
C130.0572 (13)0.0373 (10)0.0320 (10)0.0021 (10)0.0015 (10)−0.0045 (8)
C140.0441 (13)0.088 (2)0.0794 (19)0.0196 (15)−0.0051 (14)−0.0036 (16)
C150.0459 (12)0.0723 (15)0.0405 (12)0.0069 (12)0.0112 (10)0.0035 (11)

Geometric parameters (Å, °)

O1—C31.430 (3)C5—H50.98
O1—H1O0.76 (4)C6—C71.529 (3)
O2—C121.334 (2)C6—H60.98
O2—C61.477 (2)C7—C81.522 (3)
O3—C121.211 (2)C7—C111.536 (3)
O4—C111.415 (2)C7—H70.98
O4—H4O0.84 (3)C8—C91.531 (3)
O5—C131.413 (3)C8—H8A0.97
O5—H5O0.86 (3)C8—H8B0.97
C1—C101.507 (3)C9—C101.509 (3)
C1—C21.531 (3)C9—H9A0.97
C1—C51.582 (3)C9—H9B0.97
C1—H10.98C10—C141.317 (4)
C2—C31.507 (3)C11—C121.517 (3)
C2—H2A0.97C11—C131.523 (3)
C2—H2B0.97C13—H13A0.97
C3—C41.524 (3)C13—H13B0.97
C3—H30.98C14—H14A0.93
C4—C151.519 (3)C14—H14B0.93
C4—C51.544 (3)C15—H15B0.96
C4—H40.98C15—H15A0.96
C5—C61.521 (2)C15—H15C0.96
C3—O1—H1O110 (3)C8—C7—H7106.7
C12—O2—C6110.58 (15)C6—C7—H7106.7
C11—O4—H4O110 (2)C11—C7—H7106.7
C13—O5—H5O108.2 (17)C7—C8—C9111.64 (18)
C10—C1—C2116.82 (18)C7—C8—H8A109.3
C10—C1—C5116.63 (16)C9—C8—H8A109.3
C2—C1—C5103.87 (16)C7—C8—H8B109.3
C10—C1—H1106.2C9—C8—H8B109.3
C2—C1—H1106.2H8A—C8—H8B108
C5—C1—H1106.2C10—C9—C8113.23 (19)
C3—C2—C1101.96 (17)C10—C9—H9A108.9
C3—C2—H2A111.4C8—C9—H9A108.9
C1—C2—H2A111.4C10—C9—H9B108.9
C3—C2—H2B111.4C8—C9—H9B108.9
C1—C2—H2B111.4H9A—C9—H9B107.7
H2A—C2—H2B109.2C14—C10—C1122.8 (2)
O1—C3—C2112.74 (18)C14—C10—C9120.4 (2)
O1—C3—C4113.45 (19)C1—C10—C9116.8 (2)
C2—C3—C4103.36 (16)O4—C11—C12110.76 (17)
O1—C3—H3109O4—C11—C13105.43 (15)
C2—C3—H3109C12—C11—C13108.42 (17)
C4—C3—H3109O4—C11—C7114.41 (16)
C15—C4—C3113.75 (17)C12—C11—C7101.65 (15)
C15—C4—C5114.55 (17)C13—C11—C7116.10 (17)
C3—C4—C5103.48 (16)O3—C12—O2121.20 (19)
C15—C4—H4108.3O3—C12—C11127.03 (18)
C3—C4—H4108.3O2—C12—C11111.76 (16)
C5—C4—H4108.3O5—C13—C11107.92 (16)
C6—C5—C4113.89 (15)O5—C13—H13A110.1
C6—C5—C1112.26 (15)C11—C13—H13A110.1
C4—C5—C1105.39 (15)O5—C13—H13B110.1
C6—C5—H5108.4C11—C13—H13B110.1
C4—C5—H5108.4H13A—C13—H13B108.4
C1—C5—H5108.4C10—C14—H14A120
O2—C6—C5108.44 (14)C10—C14—H14B120
O2—C6—C7104.02 (14)H14A—C14—H14B120
C5—C6—C7114.98 (15)C4—C15—H15B109.5
O2—C6—H6109.7C4—C15—H15A109.5
C5—C6—H6109.7H15B—C15—H15A109.5
C7—C6—H6109.7C4—C15—H15C109.5
C8—C7—C6115.08 (17)H15B—C15—H15C109.5
C8—C7—C11116.86 (17)H15A—C15—H15C109.5
C6—C7—C11104.04 (15)
C10—C1—C2—C3−165.75 (17)C6—C7—C8—C9−59.8 (3)
C5—C1—C2—C3−35.80 (18)C11—C7—C8—C9177.73 (18)
C1—C2—C3—O1170.47 (17)C7—C8—C9—C1067.0 (3)
C1—C2—C3—C447.57 (19)C2—C1—C10—C14−1.2 (3)
O1—C3—C4—C1572.7 (2)C5—C1—C10—C14−124.9 (2)
C2—C3—C4—C15−164.87 (18)C2—C1—C10—C9−179.27 (18)
O1—C3—C4—C5−162.39 (16)C5—C1—C10—C957.1 (2)
C2—C3—C4—C5−39.96 (19)C8—C9—C10—C1491.2 (3)
C15—C4—C5—C6−95.3 (2)C8—C9—C10—C1−90.7 (2)
C3—C4—C5—C6140.34 (15)C8—C7—C11—O4−86.5 (2)
C15—C4—C5—C1141.25 (19)C6—C7—C11—O4145.49 (17)
C3—C4—C5—C116.86 (18)C8—C7—C11—C12154.14 (18)
C10—C1—C5—C617.1 (2)C6—C7—C11—C1226.08 (18)
C2—C1—C5—C6−112.97 (17)C8—C7—C11—C1336.7 (3)
C10—C1—C5—C4141.60 (18)C6—C7—C11—C13−91.3 (2)
C2—C1—C5—C411.53 (19)C6—O2—C12—O3−179.83 (19)
C12—O2—C6—C5140.81 (16)C6—O2—C12—C11−0.8 (2)
C12—O2—C6—C718.0 (2)O4—C11—C12—O340.5 (3)
C4—C5—C6—O245.5 (2)C13—C11—C12—O3−74.7 (3)
C1—C5—C6—O2165.20 (15)C7—C11—C12—O3162.5 (2)
C4—C5—C6—C7161.46 (16)O4—C11—C12—O2−138.44 (16)
C1—C5—C6—C7−78.87 (19)C13—C11—C12—O2106.34 (18)
O2—C6—C7—C8−156.38 (16)C7—C11—C12—O2−16.5 (2)
C5—C6—C7—C885.2 (2)O4—C11—C13—O5−170.20 (19)
O2—C6—C7—C11−27.24 (18)C12—C11—C13—O5−51.6 (2)
C5—C6—C7—C11−145.67 (15)C7—C11—C13—O562.0 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O4—H4O···O1i0.84 (3)1.93 (3)2.756 (2)169 (3)
O5—H5O···O3ii0.86 (3)1.99 (3)2.844 (2)176 (3)
O1—H1O···O3iii0.76 (4)2.26 (4)2.978 (3)159 (4)

Symmetry codes: (i) −x, y+1/2, −z+1/2; (ii) x+1/2, −y+1/2, −z; (iii) −x−1/2, −y+1, z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BX2222).

References

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