10α-Hy­droxy-4,9-dimethyl-13-[(4-phenyl­piperazin-1-yl)meth­yl]-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]tetra­decan-14-one

Mohamed Moumou; Ahmed Benharref; Abdelghani Oudahmane; Ahmed Elhakmaoui; Moha Berraho

doi:10.1107/S1600536811042012

. 2011 Oct 22;67(Pt 11):o2981–o2982. doi: 10.1107/S1600536811042012

10α-Hydroxy-4,9-dimethyl-13-[(4-phenylpiperazin-1-yl)methyl]-3,8,15-trioxatetracyclo[10.3.0.0^2,4.0^7,9]tetradecan-14-one

Mohamed Moumou ^a, Ahmed Benharref ^a, Abdelghani Oudahmane ^b, Ahmed Elhakmaoui ^c,^*, Moha Berraho ^a

PMCID: PMC3247384 PMID: 22220002

Abstract

The title compound, C₂₅H₃₄N₂O₅, 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 molecule contains a fused five- and ten-membered ring system. The ten-membered ring adopts an approximate chair–chair conformation, while the five-membered ring is in an envelope conformation, with the C atom closest to the hydroxy group forming the flap. The piperazine ring is in a chair conformation. In the crystal, O—H⋯O hydrogen bonds connect molecules into chains along [100]. Weak intermolecular C—H⋯O hydrogen bonds are also present.

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 ▶). For the reactivity of this sesquiterpene, see: Hwang et al. (2006 ▶); Neukirch et al. (2003 ▶); Neelakantan et al. (2009 ▶). For the synthesis, see: Moumou et al. (2010 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₅H₃₄N₂O₅
M _r = 442.54
Orthorhombic,
a = 7.7666 (5) Å
b = 9.6059 (8) Å
c = 31.181 (2) Å
V = 2326.2 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.45 × 0.36 × 0.28 mm

Data collection

Bruker X8 APEX CCD area-detector diffractometer
10922 measured reflections
2723 independent reflections
2362 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.104
S = 1.06
2723 reflections
293 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXS97 (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/S1600536811042012/lh5350sup1.cif

e-67-o2981-sup1.cif^{(29.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811042012/lh5350Isup2.hkl

e-67-o2981-Isup2.hkl^{(131KB, hkl)}

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⋯O2ⁱ	0.82	2.11	2.902 (3)	161
C14—H14B⋯O5ⁱⁱ	0.96	2.59	3.289 (3)	129
C21—H21⋯O1ⁱⁱⁱ	0.93	2.51	3.441 (4)	174

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

Acknowledgments

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

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 (Neukirch et al., 2003; Hwang et al., 2006; Neelakantan et al., 2009), in order to prepare products of value which can be used in the pharmacological industry. In this context, we have synthesed from 9α-hydroxyparthenolide the 6β,7α- epoxy-9apha hydoxy partenolide (9α-hydroxy-4,8-dimethyl-12- methylen-3,14-dioxa-tricyclo[9.3.0.0²,⁴]tetradec-7-en-13-one) (Moumou et al., 2010) and then prepared the title compound (I). The crystal structure of (I) is determined herein. The molecule contains a fused ring system and phenylpiperazine group as a substituent to a lactone ring. The molecular structure, Fig.1, shows that the lactone ring adopts an envelope conformation, as indicated by the Cremer & Pople (1975) puckering parameters Q = 0.347 (2)Å and φ = 75.6 (3)°. The ten-membered ring displays an approximate chair-chair conformation, while the piperazine ring has a perfect chair conformation with QT = 0.570 (2) Å, θ = 180.0 (2)° and φ2 = 150 (10)°. In the crystal structure, molecules are connected through O—H···O hydrogen bonds (Fig.2), forming chains along [100].

Experimental

A mixture of 6β,7α-epoxy-9α-hydoxypartenolide (9α-hydroxy-4,8-dimethyl-12- methylen-3,14-dioxa-tricyclo[9.3.0.02,4]tetradec-7-en-13-one) (0.5 g, 2 mmol) and one equivalent of 1-phenylpiperazine in EtOH (20 ml) was stirred for twelve hours at room temperature. Then the reaction was stopped by adding water (10 ml) and extracted three times with ethyl acetate (3 x 20 ml). The combined organic layers were dried over anhydrous MgSO₄, filtered and concentrated under vacuum to give 895 mg (1.8 mmol) of the title compound, which was recrystallized in ethyl acetate.