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

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

doi:10.1107/S1600536811024688

. 2011 Jun 30;67(Pt 7):o1842–o1843. doi: 10.1107/S1600536811024688

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

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

PMCID: PMC3151905 PMID: 21837209

Abstract

The title compound, C₁₉H₂₉NO₅, 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 is built up from two fused five- and ten-membered rings with the (pyrrolidin-4-yl)methyl group as a substituent. The two five-membered ring display the same envelope conformations, whereas the ten-membered ring adopts an approximate chair–chair conformation. The dihedral angle between the ten-membered ring and the lactone ring is 21.81 (9)°. An intramolecular O—H⋯N hydrogen bond stabilizes the molecular conformation. In the crystal, intermolecular C—H⋯O interactions link the molecules into chains parallel to the c axis.

Related literature

For background to the medicinal uses of the plant Anvillea radiata, see: El Hassany et al. (2004 ▶). For reactivity of this sesquiterpene see: Der-Ren et al. (2006 ▶); Neelakantan et al. (2009 ▶); Neukirch et al. (2003 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶). For conformations of ten-membered rings, see: Castaneda-Acosta et al. (1997 ▶). For related structures, see: Moumou et al. (2010 ▶); Watson & Zabel (1982 ▶). graphic file with name e-67-o1842-scheme1.jpg

Experimental

Crystal data

C₁₉H₂₉NO₅
M _r = 351.43
Orthorhombic,
a = 8.0714 (2) Å
b = 10.4571 (3) Å
c = 21.5816 (8) Å
V = 1821.56 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.89 × 0.46 × 0.21 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
8707 measured reflections
2122 independent reflections
1660 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.098
S = 1.03
2122 reflections
229 parameters
H-atom parameters constrained
Δρ_max = 0.17 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/S1600536811024688/om2443sup1.cif

e-67-o1842-sup1.cif^{(19.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811024688/om2443Isup2.hkl

e-67-o1842-Isup2.hkl^{(102.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811024688/om2443Isup3.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⋯N	0.82	2.04	2.851 (2)	172
C9—H9⋯O4ⁱ	0.98	2.38	3.260 (2)	149
C10—H10⋯O2ⁱⁱ	0.98	2.46	3.392 (3)	158
C19—H19B⋯O5ⁱⁱⁱ	0.97	2.59	3.357 (3)	136

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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 the X-ray measurements.

supplementary crystallographic information

Comment

Our work lies within the framework of the valorization of medicinals plants and concerning the Anvillea radiata. The main constituent of the chloroform extract of aerial parts of this plant is 9α-hydroxypartenolide (El Hassany et al., 2004). The reactivity of this sesquiterpene lactone and its derivatives has been the subject of several studies (Neukirch et al., 2003; Der-Ren et al., 2006; Neelakantan et al., 2009), in order to prepare products with a high added value that can be used in the pharmacology industry. In this context, we have treated the 9α-hydroxypartenolide with one equivalent of meta-chloroperbenzoic acid (mCPBA), as we have done for its isomer the 9β-hydroxypartenolide (Moumou et al.,2010), and we got the 6β,7α-epoxy-9α-hydroxypartenolide in a yield of 75% (see Figure 3). This latter was treated with an equivalent of pyrrolodine and gives the title compound (I) in a yield of 95%. The molecule contains two fused rings which exhibit different conformations with a pyrolidin ring as a substituent to the lactone ring. The molecular structure of (I), Fig. 1, shows that the two five membered rings adopt an envelope conformation, as indicated by Cremer & Pople (1975) puckering parameters Q = 0.298 (2) Å and φ = 77.5 (4)° for the lactone ring and Q = 0.362 (3) Å, φ2 = 6.4 (6)° for the pyrolidin ring. The ten-membered ring displays an approximate chair-chair conformation, this is the typical conformation observed for other sesquiterpenes lactones (Moumou et al., 2010; Watson & Zabel, 1982; Castaneda-Acosta et al., 1997). In the crystal structure, molecules are linked into supramolecular chains (Fig. 2) parallel to the c axis by C—H···O hydrogen bonds (Table 1). In addition an intramolecular O—H···N hydrogen bond is also observed.

Experimental

The mixture of 6β,7α-epoxy-9α hydoxy partenolide (0.5 g, 2 mmol) and one equivalent of pyrolidine in EtOH (20 ml) was stirred for one night at room temperature. The next day 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 666 mg (1.9 mmol) of solid which was recrystallized in ethyl acetate.