(1S,2R,3R,8R,10S)-3-Chloro-2,8-dihy­droxy-3,7-dimethyl-11-methyl­idene-13-oxabicyclo­[8.3.0]tridec-6-en-12-one

Mohamed Moumou; Ahmed Benharref; Jean-Claude Daran; Ahmed Elhakmaoui; Mohamed Akssira; Moha Berraho

doi:10.1107/S1600536811039717

. 2011 Oct 5;67(Pt 11):o2826–o2827. doi: 10.1107/S1600536811039717

(1S,2R,3R,8R,10S)-3-Chloro-2,8-dihydroxy-3,7-dimethyl-11-methylidene-13-oxabicyclo[8.3.0]tridec-6-en-12-one

Mohamed Moumou ^a, Ahmed Benharref ^a, Jean-Claude Daran ^b, Ahmed Elhakmaoui ^c,^*, Mohamed Akssira ^c, Moha Berraho ^a

PMCID: PMC3247566 PMID: 22219871

Abstract

The title compound, C₁₅H₂₁ClO₄, was synthesized from 9α-hydroxyparthenolide (9α-hydroxy-4,8-dimethyl-12-methylen-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 molecule is built up from fused five- and ten-membered rings. The five-membered lactone ring has an envelope conformation with the flap atom, C(H)-C-C(H), displaced by 0.2325 (15) Å from the mean plane through the remaining four atoms, whereas the ten-membered ring displays an approximate chair–chair conformation. The dihedral angle between the two rings is 66.4 (2)°. In the crystal, molecules are linked into chains propagating along the a axis by O—H⋯O hydrogen bonds.

Related literature

For the isolation and biological activity of 9α-hydroxyparthenolide, see: El Hassany et al. (2004 ▶). For the reactivity of this sesquiterpene, see: Castaneda-Acosta et al. (1993 ▶); Neukirch et al. (2003 ▶); Hwang et al. (2006 ▶); Neelakantan et al. (2009 ▶). For conformational analysis, see: Cremer & Pople (1975 ▶)

Experimental

Crystal data

C₁₅H₂₁ClO₄
M _r = 300.77
Orthorhombic,
a = 8.0224 (2) Å
b = 12.1532 (2) Å
c = 15.4147 (4) Å
V = 1502.90 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 180 K
0.35 × 0.27 × 0.17 mm

Data collection

Agilent Xcalibur Eos Gemini ultra diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.889, T _max = 1.000
8982 measured reflections
3053 independent reflections
2944 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.070
S = 1.04
3053 reflections
185 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.21 e Å⁻³
Absolute structure: Flack (1983 ▶), 614 Friedel pairs
Flack parameter: −0.06 (5)

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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/S1600536811039717/im2319sup1.cif

e-67-o2826-sup1.cif^{(18.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811039717/im2319Isup2.hkl

e-67-o2826-Isup2.hkl^{(146.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811039717/im2319Isup3.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
O3—H3⋯O4ⁱ	0.82	1.96	2.763 (1)	167
O4—H4⋯O3ⁱⁱ	0.82	2.17	2.980 (1)	171

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for financial support.

supplementary crystallographic information

Comment

Our work lies within the framework of the evaluation of medicinal plants and in particular, Anvillea radiata. The main constituent of the chloroform extract of the aerial parts of Anvillea radiata is 9α-hydroxyparthenolide (El Hassany et al., 2004). The reactivity of this sesquiterpene lactone and its derivatives has been the subject of several studies (Castaneda-Acosta et al., 1993; Neukirch et al., 2003; Hwang et al., 2006; Neelakantan et al., 2009), in order to prepare products with a high added value that can be used in the pharmacological industry. In the same context, we have treated 9α-hydroxyparthenolide with 5% of titanium tetrachloride (TiCl₄)and obtained (1S, 2R, 3R, 8R, 10S)-3-chloro-2,8- dihydroxy-3,7-dimethyl-11-methylene-13-oxabicyclo[8.3.0]tridec-6-en-12-one with a yield of 52%. The structure of this new product was determined by its single-crystal X-ray structure. The molecule contains two fused rings which exhibit different conformations. The molecular structure of the title compound, Fig.1, shows the lactone ring to adopt an envelope conformation, as indicated by Cremer & Pople (1975) puckering parameters QT = 0.147 (2) Å and φ2 = 58.1 (5)°. The ten-membered ring displays an approximate chair-chair conformation.In the crystal structure, molecules are linked into chains (Fig. 2) running along the a axis by intermolecular O—H···O hydrogen bonds (Table 1). Owing to the presence of Cl atom, the absolute configuration could be fully confirmed, by refining the Flack parameter (Flack, 1983) as C1(S), C2(R), C3(R), C8(R)and C10(S).

Experimental

To a solution of 9α-hydroxyparthenolide (500 mg, 1.89 mmol) in 20 ml dichloromethane are added in small portions and carefully a catalytic amount (5%) of titanium tetrachloride (TiCl₄). The reaction mixture was kept at room temperature and stirred for 3 h. Afterwards it was hydrolysed with 20 ml of water and extracted three times with dichloromethane (20 mL). The organic phases are combined, dried over anhydrous Na₂SO₄ and then evaporated under reduced pressure. The resulting residue is purified by chromatography on silica gel with hexane /ethyl acetate (30/70) as eluent. This allowed us to isolate in pure 291 mg (0,98 mmol, 52%) of (1S, 2R, 3R, 8R, 10S)-3-chloro-2,8-dihydroxy-3,7-dimethyl-11-methylene- 13-oxabicyclo[8.3.0]tridec-6-en-12-one. The title compound was recrystallized from ethyl acetate to produce crystals suitable for X-ray diffraction.