9α-Hy­droxy-12-{[4-(4-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4,8-dimethyl-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one

Mohamed Moumou; Ahmed Benharref; Jean-Claude Daran; Fouad Mellouki; Moha Berraho

doi:10.1107/S1600536812003662

. 2012 Feb 4;68(Pt 3):o589–o590. doi: 10.1107/S1600536812003662

9α-Hydroxy-12-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-4,8-dimethyl-3,14-dioxatricyclo[9.3.0.0^2,4]tetradec-7-en-13-one

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

PMCID: PMC3297315 PMID: 22412505

Abstract

The title compound, C₂₆H₃₆N₂O₅, 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), wich 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 with the methoxyphenylpiperazine group as a substituent. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring a flattened envelope conformation; the C(H)—C—C(H) atoms representing the flap lie out of the mean plane through the remaining four atoms by 0.343 (3) Å. The dihedral angle between the mean planes of the ten-membered ring and the lactone ring is 18.12 (14)°. An intramolecular O—H⋯N hydrogen bond occurs. The crystal structure features weak C—H⋯O interactions.

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 ring-puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₆H₃₆N₂O₅
M _r = 456.57
Orthorhombic,
a = 6.7066 (7) Å
b = 11.9033 (11) Å
c = 30.322 (4) Å
V = 2420.6 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 180 K
0.33 × 0.17 × 0.04 mm

Data collection

Agilent Xcalibur Sapphire1 (long nozzle) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.732, T _max = 1.000
14543 measured reflections
4925 independent reflections
3663 reflections with I > 2σ(I)
R _int = 0.055

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.130
S = 1.04
4925 reflections
303 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.23 e Å⁻³

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/S1600536812003662/ds2172sup1.cif

e-68-0o589-sup1.cif^{(32.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812003662/ds2172Isup2.hkl

e-68-0o589-Isup2.hkl^{(236.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812003662/ds2172Isup3.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⋯N1	0.84	2.14	2.977 (4)	170
C2—H2⋯O12ⁱ	1.00	2.42	3.225 (4)	137
C5—H5B⋯O3ⁱⁱ	0.99	2.45	3.310 (4)	145
C7—H7⋯O14ⁱⁱⁱ	0.95	2.50	3.198 (4)	130
C15—H15A⋯O12ⁱ	0.99	2.57	3.413 (4)	143
C15—H15A⋯O14ⁱ	0.99	2.50	3.469 (4)	165

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

Acknowledgments

The authors thank Professor El Ammari for discussions on the refinement of the structure.

supplementary crystallographic information

Comment

Our work lies within the framework of the valorization of medicinals plants and concerning the Anvillea radiata wich is a plant that grows in northern Africa and particularly found 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), hypoglycemic activity (Qureshi et al., 1990), and has been reported to have antitumoral 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 pharmacology and cosmetics industry, we studied the chemical reactivity of this major constituent of Anvillea radiata. Thus, treatment of this sesquiterpene lactone by an equivalent amount of 1-(4-methoxyphenylpiperazine) in ethanol led to the title compound with a yield of 78%. The crystal structure of (I) is reported herein. The molecule contains a fused ring system and methoxyphenylpiperazine group as a substituent to a lactone ring. The molecular structure of (I), Fig. 1, shows the lactone ring to adopt an envelope conformation, as indicated by Cremer & Pople (1975) puckering parameters Q = 0.216 (3) Å and φ = 69.7 (8)°. The atom C11 deviate from the mean plane through other four atoms in the ring by 0.343 (2) Å. The ten-membered ring displays an approximate chair–chair conformation, while the piperazine ring has a perfect chair conformation with QT = 0.557 (3) Å, θ = 3.4 (3)° and φ2 = 33 (6)°. In the crystal structure, the molecules are linked by C—H···O intermolecular hydrogen bonds into chains along the b axis (Table 1, Fig.2). In addition an intramolecular O—H···N hydrogen bond is also observed.

Experimental

The mixture of 9α-hydroxyparthenolide (1 g, (3.78 mmol) and one equivalent of 1-(4-methoxyphenylpipirazine) in EtOH (30 ml) was stirred for one night at room temperature. The next day the reaction was stopped by adding water (20 ml) and extracted three times with ethyl acetate (3 × 30 ml). The combined organic layers were dried over anhydrous MgSO₄, filtered and concentrated under vacuum to give 1.34 g (2.94 mmol) of the title compound, which was recrystallized in ethyl acetate.