5,9-Dihy­droxy-9-methyl-3,6-dimethyl­ene-3a,4,5,6,6a,7,8,9,9a,9b-deca­hydro­azuleno[4,5-b]furan-2(3H)-one

Mohamed Moumou; Ahmed Benharref; Moha Berraho; Lahcen El Ammari; Mohamed Akssira; Ahmed Elhakmaoui

doi:10.1107/S160053681102352X

. 2011 Jun 22;67(Pt 7):o1760–o1761. doi: 10.1107/S160053681102352X

5,9-Dihydroxy-9-methyl-3,6-dimethylene-3a,4,5,6,6a,7,8,9,9a,9b-decahydroazuleno[4,5-b]furan-2(3H)-one

Mohamed Moumou ^a,^*, Ahmed Benharref ^a, Moha Berraho ^a, Lahcen El Ammari ^b, Mohamed Akssira ^c, Ahmed Elhakmaoui ^c

PMCID: PMC3151879 PMID: 21837142

Abstract

The title compound, C₁₅H₂₀O₄, was synthesized from 9α-hydroxyparthenolide (9α-hydroxy-4,8-dimethyl-12-methylene-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one), which was isolated from the chloroform extract of the aerial parts of Anvillea radiata. The seven-membered ring has a chair conformation, while the five-membered rings display twisted conformations. The dihedral angle between the seven-membered ring and the lactone ring is 21.69 (10)°. In the crystal, molecules are linked into chains propagating along the c axis by intermolecular O—H⋯O hydrogen bonds; an intramolecular O—H⋯O link also occurs.

Related literature

For background to the medicinal uses of the plant Anvillea radiata, see: Abdel Sattar et al. (1996 ▶); Bellakhdar (1997 ▶); El Hassany et al. (2004 ▶); Qureshi et al. (1990 ▶). For the reactivity of this sesquiterpene, see: El Haib et al. (2011 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₅H₂₀O₄
M _r = 264.31
Orthorhombic,
a = 6.4210 (14) Å
b = 13.504 (3) Å
c = 15.619 (3) Å
V = 1354.4 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.50 × 0.33 × 0.08 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
14445 measured reflections
1610 independent reflections
1473 reflections with I > 2σ(I)
R _int = 0.051

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.097
S = 1.08
1610 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2 and SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶)and PLATON (Spek, 2009 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681102352X/sj5165sup1.cif

e-67-o1760-sup1.cif^{(16.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681102352X/sj5165Isup2.hkl

e-67-o1760-Isup2.hkl^{(77.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681102352X/sj5165Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3	0.82	2.42	3.015 (2)	131
O4—H4⋯O2ⁱ	0.82	2.03	2.819 (2)	162

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.

supplementary crystallographic information

Comment

Anvillea radiata is a plant that grows in northern Africa and particularly in the two Maghreb countries, Morocco and Algeria. This plant is used in traditional local medicine for the treatment of dysentery, gastric-intestinal disorders (Bellakhdar, 1997), and hypoglycemic activity (Qureshi et al., 1990), and has been reported to have antitumor activity (Abdel Sattar et al., 1996). In our study of different Moroccan endemic plants, we have demonstrated that the aerial parts of Anvillea radiata could be used as a renewable source of 9-hydroxyparthenolide (El Hassany, et al., 2004). In order to prepare products with high added value that can be used in the pharmacology and cosmetics industries, we have studied the chemical reactivity of this major constituent of Anvillea radiata. Thus, treatment of this sesquiterpene with methane sulfonic acid (MSA) or p-toluene sulfonic acid (PTSA) in dichloromethane (El Haib et al., 2011) led to 5,9-dihydroxy-9-methyl- 3,6-dimethylene-decahydro-azulene [4,5-b] furan-2-one with a yield of 45%. The molecule contains three fused rings which exhibit different conformations. The molecular structure of (I), Fig.1, shows the five membered rings to adopt a twisted conformations, as indicated by the Cremer & Pople (1975) puckering parameters Q = 0.233 (2) Å and φ = 121.1 (5)° for the lactone ring and Q = 0.426 (2) Å, φ = 264.5 (3)° for the other five-membered ring. The seven-membered ring has a chair conformation with QT = 0.8255 (20) Å, θ2 = 36.20 (15)°, φ2 = 89.3 (2)° and φ3 =207.07 (18). In the crystal structure, molecules are linked into chains (Fig. 2) running along the c axis by intermolecular O4—H2···O3 hydrogen bonds. In addition an intramolecular O2—H2···O3 hydrogen bond is also observed.

Experimental

Methane sulfonic acid (MSA) or p-toluene sulfonic acid (PTSA) (6x10_-2mmol) was added to a stirred solution of 9α-hydroxyparthenolide (1 g, 4 mmol) in dichloromethane (10 ml). The reaction mixture is left stirring for two hours at room temperature. After completion of the reaction, a saturated solution of NaHCO₃ was added and the resulting mixture is extracted three times (3x20mL) with dichloromethane. The organic phases are combined and dried over Na₂SO₄ and evaporated under vacuum. Chromatography of the residue obtained on a column of silica gel eluting with hexane - ethyl acetate (40/60) allowed the isolation of pure 5,9-dihydroxy-9-methyl- 3,6-dimethylene-decahydro-azulene [4,5-b] furan-2-one (446 mg, 1.80 mmol). The title compound was recrystallized from its ethyl acetate solution.