(Z)-6-Hy­droxy-1a,5-dimethyl-8-[(morpholin-4-yl)meth­yl]-2,3,6,7,7a,8,10a,10b-octa­hydro­oxireno[2′,3′:9,10]cyclo­deca­[1,2-b]furan-9(1aH)-one

Mohamed Moumou; Ahmed Benharref; Moha Berraho; Lahcen El Ammari; Mohamed Akssira; Ahmed Elhakmaoui

doi:10.1107/S1600536811022616

. 2011 Jun 18;67(Pt 7):o1698–o1699. doi: 10.1107/S1600536811022616

(Z)-6-Hydroxy-1a,5-dimethyl-8-[(morpholin-4-yl)methyl]-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-9(1aH)-one

Mohamed Moumou ^a,^*, Ahmed Benharref ^a, Moha Berraho ^a, Lahcen El Ammari ^b, Mohamed Akssira ^c, Ahmed Elhakmaoui ^c

PMCID: PMC3151749 PMID: 21837095

Abstract

The title compound, C₁₉H₂₉NO₅, was synthesized from 9α-hydroxyparthenolide (9α-hydroxy-4,8-dimethyl-12-methylen-3,14-dioxatricyclo[9.3.0.0²,⁴]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 (morpholin-4-yl)methyl group as a substituent. The five-membered lactone ring has an envelope conformation, whereas the ten-membered and the morpholine rings display approximate chair–chair and chair conformations, respectively. The dihedral angle between the ten-membered ring and the lactone ring is 27.93 (6)°. The crystal structure is stabilized by weak intermolecular C—H⋯O hydrogen-bond interactions. An intramolecular O—H⋯N hydrogen bond also occurs.

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 the reactivity of this sesquiterpene see: Der-Ren et al. (2006 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₉H₂₉NO₅
M _r = 351.43
Monoclinic,
a = 11.7539 (3) Å
b = 6.8304 (2) Å
c = 11.8585 (3) Å
β = 101.328 (2)°
V = 933.50 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.45 × 0.33 × 0.12 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
11514 measured reflections
2086 independent reflections
1987 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.095
S = 1.07
2086 reflections
229 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.13 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/S1600536811022616/zl2378sup1.cif

e-67-o1698-sup1.cif^{(19.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811022616/zl2378Isup2.hkl

e-67-o1698-Isup2.hkl^{(100.5KB, 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—H4A⋯N	0.82	2.24	3.051 (2)	172
C2—H2B⋯O2ⁱ	0.97	2.51	3.324 (3)	142
C10—H10⋯O1ⁱⁱ	0.98	2.47	3.270 (2)	138

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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

Anvillea radiata is a plant that grows in northern Africa and particularly in the two Maghreb countries, Morocco and Algeria. This plant is used in the traditional local medicine for the treatment of dysentery, gastric-intestinal disorders (Bellakhdar, 1997), and hypoglycemic activity (Qureshi et al., 1990), and has been reported to have antitumor 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 a high added value that can be used in the pharmacology and cosmetics industry, we studied the chemical reactivity of this major constituent of Anvillea radiata. Thus, treatment of this sesquiterpene with an equivalent amount of morpholine in ethanol (Der-Ren et al., 2006) led to (Z)-6-hydroxy-1a,5-dimethyl-8-(morpholinomethyl)-2,3,6,7,7a,8,10a,10b- octahydrooxireno[2',3': 9,10]cyclodeca[1,2-b]furan-9(1aH)-one, in a yield of 90%. The structure of this new product was determined by ¹H and ¹³C NMR spectral analysis, IR and mass spectrometry, and was confirmed by its single-crystal X-ray structure. The molecule contains two fused rings which exhibit different conformations with a morpholin ring 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 Cremer & Pople (1975) puckering parameters Q = 0.2O83(14) Å and φ = 68.2 (4)°. The ten-membered ring displays an approximate chair-chair conformation, while the morpholin ring has a perfect chair conformation with QT = 0.5690 (19) Å, θ2 = 0.00 (19)°, φ2 = 135 (6)°. In the crystal structure, the molecules are linked by C—H···O intermolecular hydrogen bonds into zigzag chains along the a axis (Fig.2). In addition an intramolecular O—H···N hydrogen bond is also observed.

Experimental

A mixture of 9α-hydroxyparthenolide (0.5 g, 2 mmol) and one equivalent of morpholine 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 600 mg wite solid (1.8 mmol) which was recrystallized in ethyle acetate. Mp = 474–475 K (ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 1.30 (H-13, s, 3H); 1.70 (H-14, s, 3H); 2.55 (H-15, m, 2H); 2.68 (H-16, H-19, t, J = 4.5 Hz, 4H); 3.10 (H-10, d, J = 8.70 Hz, 1H); 3.68 (H-17 H-18, t, J = 4.5 Hz, 4H); 3.95 (H-6, dd, J₁ = 1.2 Hz and J₂ = 11.5 Hz, 1H); 4.55 (H-9, dd, J₁ = 8,7 Hz, and J₂ = 9.3 Hz, 1H); 5.55 (H-4, dd, J₁ = 2,4 and J₂ = 12, 0 Hz, 1H); ¹³C RMN (300 MHZ, CDCl₃)δ 16.83 (C-13); 17.13 (C-14); 23.04 (C-3); 36.65 (C-2); 37.09 (C-7); 37.83 (C-8); 44.27 (C-11); 54.03 (C-16, C-19); 59.95 (C-15); 60.86 (C-10); 66.17 (C-1); 67.69 (C-17, C-18); 70.94 (C-6); 82.87 (C-9); 120.97 (C-4); 137.37 (C-5); 177.50( C-12); IR (KBr): 3433 cm^-1 (OH), 1766 cm^-1 (lactone carbonyl), 1668 cm^-1 (double bond); MS (EI, 70 eV): 351(M⁺).