10α-Hy­droxy-13-{[4-(4-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

Mohamed Moumou; Ahmed Benharref; Jean Claude Daran; Rachid Outouch; Moha Berraho

doi:10.1107/S1600536812005818

. 2012 Feb 17;68(Pt 3):o715–o716. doi: 10.1107/S1600536812005818

10α-Hydroxy-13-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-4,9-dimethyl-3,8,15-trioxatetracyclo[10.3.0.0^2,4.0^7,9]pentadecan-14-one

Mohamed Moumou ^a, Ahmed Benharref ^b, Jean Claude Daran ^c, Rachid Outouch ^b,^*, Moha Berraho ^b

PMCID: PMC3295488 PMID: 22412599

Abstract

The title compound, C₂₆H₃₆N₂O₆, was synthesized from 9α-hydroxyparthenolide (9α-hydroxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo[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 with two additional epoxy ring systems and a 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 shows an envelope conformation with the C atom closest to the hydroxy group forming the flap. The molecular conformation is determined by an O—H⋯N hydrogen bond between the hydroxy group and a piperazine N atom. The crystal structure is built up by weak C—H⋯O interactions.

Related literature

For background to the medicinal uses of the plant Anvillea adiata, see: Abdel Sattar et al. (1996 ▶); El Hassany et al. (2004 ▶); Qureshi et al. (1990 ▶). For the reactivity of this sesquiterpene, see: Hwang et al. (2006 ▶); Neukirch et al. (2003 ▶); Neelakantan et al. (2009 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶). For the synthetic procedure, see: Moumou et al. (2010 ▶).

Experimental

Crystal data

C₂₆H₃₆N₂O₆
M _r = 472.57
Orthorhombic,
a = 8.0770 (7) Å
b = 10.2667 (10) Å
c = 28.937 (3) Å
V = 2399.5 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 180 K
0.27 × 0.21 × 0.06 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
2810 independent reflections
1704 reflections with I > 2σ(I)
R _int = 0.091

Refinement

R[F ² > 2σ(F ²)] = 0.072
wR(F ²) = 0.188
S = 1.04
2810 reflections
312 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.32 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/S1600536812005818/im2357sup1.cif

e-68-0o715-sup1.cif^{(32.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812005818/im2357Isup2.hkl

e-68-0o715-Isup2.hkl^{(135.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812005818/im2357Isup3.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
O1—H1⋯N1	0.82	2.10	2.901 (6)	165
C9—H9B⋯O1ⁱ	0.97	2.50	3.345 (7)	145
C14—H14⋯O5ⁱⁱ	0.98	2.49	3.447 (7)	165
C15—H15⋯O2ⁱ	0.98	2.51	3.342 (7)	142
C24—H24⋯O2ⁱ	0.98	2.33	3.185 (7)	146
C33—H33⋯O3ⁱⁱⁱ	0.93	2.53	3.335 (10)	145

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

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 have been the subject of several studies (Neukirch et al., 2003; Hwang et al., 2006; Neelakantan et al., 2009), in order to prepare products with high value which can be used in the pharmacological industry. In this context, we have synthesed, from 9α-hydroxyparthenolide, the 1β,10α-epoxy-9α-hydoxypartenolide (10α-hydroxy-4,9-dimethyl-13-methylen-3,8,15-dioxa-tetracyclo [10.3.0.0^2,4.0^7,9] pentadecan-14-one) (Moumou et al., 2010). This epoxy-hydroxypartenolide treated with one equivalent of 1-(4-methoxyphenyl)-piperazine gives the title compound (I). The crystal structure of (I) is reported herein. The molecule contains a fused ring system and the methoxyphenyl-piperazine group as a substituent to the lactone ring. The molecular structure of (I), Fig.1, shows the lactone ring to adopt an envelope conformation, as indicated by the puckering parameters Q = 0.297 (3) Å and φ =101.7 (8)° (Cremer & Pople, 1975). The ten-membered ring displays an approximate chair-chair conformation, while the piperazine ring has a perfect chair conformation with QT = 0.579 (3) Å, θ = 2.0 (4)° and φ2 =359 (10)°. In the crystal, C—H···O hydrogen bonding links the molecules into sheets lying parallel to the bc plane (Table 1, Fig.2). In addition, an intramolecular O1—H1···N1 hydrogen bond is also observed.

Experimental

The mixture of 1β,10α-epoxy-9α-hydoxypartenolide (10α-hydroxy- 4,9-dimethyl-13-methylen-3,8,15-dioxa-tetracyclo [10.3.0.0^2,4.0^7,9] pentadecan-14-one) (500 mg, 1.78 mmol) and one equivalent of 1-(4-methoxyphenyl-piperazine) in EtOH (20 ml) was stirred for twelve hours at room temperature. Then the reaction was stopped by adding water (10 ml) and the solution was extracted with chloroform (3 x 20 ml). The combined organic layers were dried over anhydrous MgSO₄, filtered and concentrated under vacuum to give 730 mg (1.8 mmol) of the title compound (yield: 90%). Recrystallization was performed from in ethyl acetate.