9-Hy­droxy-4,8-dimethyl-12-(pyrrolidin-1-ylmeth­yl)-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one

Mohamed Moumou; Ahmed Benharref; Daniel Avignant; Abdelghani Oudahmane; Mohamed Akssira; Moha Berraho

doi:10.1107/S1600536811030467

. 2011 Aug 2;67(Pt 9):o2226–o2227. doi: 10.1107/S1600536811030467

9-Hydroxy-4,8-dimethyl-12-(pyrrolidin-1-ylmethyl)-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one

Mohamed Moumou ^a,^*, Ahmed Benharref ^a, Daniel Avignant ^b, Abdelghani Oudahmane ^b, Mohamed Akssira ^c, Moha Berraho ^a

PMCID: PMC3200593 PMID: 22065010

Abstract

The title compound, C₁₉H₂₉O₄, 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 two fused five- and ten-membered rings with the pyrrolidin-1-ylmethyl group as a substituent. The five-membered lactone ring has an envelope conformation, whereas the ten-membered and pyrrolidine rings display approximate chair–chair and twisted conformations, respectively. The dihedral angle between the ten-membered ring and the lactone ring is 18.01 (19)°. An intramolecular O—H⋯N hydrogen bond occurs. The crystal structure is stabilized by weak intermolecular C—H⋯O hydrogen-bonding interactions.

Related literature

For the isolation and biological activity of 9α-hydroxyparthenolide, see: Abdel Sattar et al. (1996 ▶); El Hassany et al. (2004 ▶). For the reactivity of this sesquiterpene, see: Castaneda-Acosta et al. (1993 ▶); Neukirch et al. (2003 ▶); Der-Ren et al. (2006 ▶); Neelakantan et al. (2009 ▶). For conformational analysis, see: Cremer & Pople (1975 ▶)

Experimental

Crystal data

C₁₉H₂₉NO₄
M _r = 335.43
Orthorhombic,
a = 8.1389 (6) Å
b = 10.1788 (7) Å
c = 21.7669 (15) Å
V = 1803.3 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.30 × 0.27 × 0.18 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.634, T _max = 0.746
7656 measured reflections
2110 independent reflections
1220 reflections with I > 2σ(I)
R _int = 0.053

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.121
S = 0.99
2110 reflections
222 parameters
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.15 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/S1600536811030467/zl2390sup1.cif

e-67-o2226-sup1.cif^{(26KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030467/zl2390Isup2.hkl

e-67-o2226-Isup2.hkl^{(101.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811030467/zl2390Isup3.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
O4—H4⋯N	0.82	2.17	2.964 (4)	164
C1—H1⋯O4ⁱ	0.98	2.57	3.533 (4)	167
C11—H11⋯O1ⁱⁱ	0.98	2.50	3.403 (4)	154

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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 the X-ray measurements.

supplementary crystallographic information

Comment

The natural sesquiterpene lactone 9α-hydroxypartenolide is the main constituent of the chloroform extract of the aerial parts of Anvillea radiata (El Hassany et al., 2004) and of Anvillea garcini (Abdel Sattar et al., 1996). 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; Der-Ren et al., 2006; Neelakantan et al., 2009), with the aim 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 one equivalent of pyrrolidine and obtained 9-hydroxy-4,8-dimethyl-12-pyrrolidin-1-ylmethyl-3, 14-dioxatricyclo[9.3.0.0^2,4] tetradec -7-en-13-one with a good yield of 84%. The structure of this new derivative of 9α-hydroxypartenolide was determined by its single-crystal X-ray structure. The molecule contains two fused rings which exhibit different conformations with a pyrrolidine ring as a substituent to the lactone ring. 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 = 0.291 (4) Å and φ2 = 78.1 (7)°. The ten-membered ring displays an approximate chair-chair conformation, while the pyrrolidine ring has a twisted conformation with QT = 0.377 (4) Å, φ2 = 15.0 (8)°. In the crystal structure, molecules are connected through C—H···O hydrogen bonds, forming chains running along the b axis. (Fig.2). In addition an intramolecular O—H···N hydrogen bond is also observed.

Experimental

A mixture of 9α-hydoxypartenolide (300 mg, 1.13 mmol) and one equivalent of pyrrolidine in EtOH (20 ml) was stirred for one night at room temperature. The next day the reaction was stopped by adding 10 ml of water and extracted three times with ethyl acetate (3 × 20 ml). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give 315 mg (0.94 mmol, 84%) of 9-hydroxy-4,8-dimethyl-12-pyrrolidin- 1-ylmethyl-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one. The title compound was recrystallized in ethyl acetate.