Cynaratriol, a sesquiterpene lactone from Centaurea musimomum

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.

The title compound [systematic name: 3,8-dihydroxy-3-(hydroxymethyl)-9-methyl-6-methylenedecahydroazuleno-[4,5-b]furan-2(3H)-one], C 15 H 22 O 5 , 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 1 H NMR and MS spectroscopy, as well as the the 11-hydroxymethyl, 3hydroxy and 4-methyl stereochemistry. The crystal structure is built through a network of O-HÁ Á ÁO 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). For the structures of several guaianolide type sesquiterpene lactones isolated from the chloroform-soluble part of Centaurea musimomum, see: Medjroubi et al. (1997Medjroubi et al. ( , 2003Medjroubi et al. ( , 2005; Gonzá lez-Platas et al. (1999). Cynaratriol was previously isolated from Cynara species, see: von Heinz et al. (1979). For related structures, see: Oksuz et al. (1993); Gonzá lez-Platas et al. (1999).  Table 1 Hydrogen-bond geometry (Å , ).  (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(CH 3 ), 0.99(CH 2 ), 1.00(CH) Å and included in the refinement in a ridingmodel approximation with U iso (H) = 1.2U eq (C) and U iso (H) = 1.5U eq 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.

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 ex-supplementary materials sup-3 tract 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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.