supplementary materials


lh5393 scheme

Acta Cryst. (2012). E68, o167-o168    [ doi:10.1107/S1600536811053207 ]

10[alpha]-Hydroxy-4,9-dimethyl-13-(morpholin-4-ylmethyl)-3,8,15-trioxatetracyclo[10.3.0.02,4.07,9]pentadecan-14-one

M. Moumou, A. Benharref, A. Oudahmane, F. Mellouki and M. Berraho

Abstract top

The title compound, C19H29NO6, was synthesized from 9[alpha]-hydroxyparthenolide (9[alpha]-hydroxy-4,8-dimethyl-12-methylene-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 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. In the crystal, weak C-H...O hydrogen bonds connect the molecules into layers parallel to (001). An intramolecular O-H...N hydrogen bond is also present.

Comment top

Our work lies within the framework of the valorization of medicinals plants and concerns 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 have 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 9α-hydroxyparthenolide from 6β,7α-epoxy-9alpha 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 compond (I). The crystal structure of (I) is determined herein. The molecule contains a fused ring system and morpholine 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 Cremer & Pople (1975) puckering parameters Q = 0.189 (3)Å and φ = 66.0 (8)°. The ten-membered ring displays an approximate chair-chair conformation, while the morpholine ring has a perfect chair conformation with QT = 0.567 (4) Å, θ = 0.0 (3)° and φ2 = 157 (43)°. In the crystal structure, molecules are connected through weak C—H···O hydrogen bonds (Fig.2), forming layers parallel to (001). In addition, an intramolecular O—H···N hydrogen bond is also observed.

Related literature top

For background to the medicinal uses of the plant Anvillea radiata, see: 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 synthesis see: Moumou et al. (2010).

Experimental top

A mixture of 6β,7α-epoxy-9apha hydoxy partenolide (0.5 g, 1.89 mmol) and one equivalent of morpholine in EtOH (20 ml) was stirred for one 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 628 mg (1.79 mmol) of the title compound which was recrystallized from ethyl acetate.

Refinement top

All H atoms were fixed geometrically and treated as riding with C—H = 0.96 Å (methyl), 0.97 Å (methylene), 0. 98Å (methine) with Uiso(H) = 1.2Ueq (methylene, methine) or Uiso(H) = 1.5Ueq (methyl, OH). In the absence of significant anomalous scattering, the absolute configuration could not be reliably determined and thus the Friedel pairs were merged.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); 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).

Figures top
[Figure 1] Fig. 1. : Molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii.
[Figure 2] Fig. 2. : Packing view showing the C–H···O and O–H···N hydrogen bonds as dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
10α-Hydroxy-4,9-dimethyl-13-(morpholin-4-ylmethyl)-3,8,15- trioxatetracyclo[10.3.0.02,4.07,9]pentadecan-14-one top
Crystal data top
C19H29NO6F(000) = 396
Mr = 367.43Dx = 1.300 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 2070 reflections
a = 11.6772 (9) Åθ = 3.6–26.4°
b = 6.9524 (4) ŵ = 0.10 mm1
c = 11.8244 (9) ÅT = 296 K
β = 102.160 (2)°Prism, colourless
V = 938.42 (12) Å30.65 × 0.45 × 0.26 mm
Z = 2
Data collection top
Bruker X8 APEXII CCD
diffractometer
1661 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.032
graphiteθmax = 26.4°, θmin = 3.6°
φ and ω scansh = 1414
7793 measured reflectionsk = 68
2069 independent reflectionsl = 1413
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H-atom parameters constrained
wR(F2) = 0.110 w = 1/[σ2(Fo2) + (0.0604P)2 + 0.079P]
where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max < 0.001
2069 reflectionsΔρmax = 0.20 e Å3
239 parametersΔρmin = 0.23 e Å3
1 restraintExtinction correction: SHELXL97 (Sheldrick,2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.047 (7)
Crystal data top
C19H29NO6V = 938.42 (12) Å3
Mr = 367.43Z = 2
Monoclinic, P21Mo Kα radiation
a = 11.6772 (9) ŵ = 0.10 mm1
b = 6.9524 (4) ÅT = 296 K
c = 11.8244 (9) Å0.65 × 0.45 × 0.26 mm
β = 102.160 (2)°
Data collection top
Bruker X8 APEXII CCD
diffractometer
1661 reflections with I > 2σ(I)
7793 measured reflectionsRint = 0.032
2069 independent reflectionsθmax = 26.4°
Refinement top
R[F2 > 2σ(F2)] = 0.044H-atom parameters constrained
wR(F2) = 0.110Δρmax = 0.20 e Å3
S = 1.07Δρmin = 0.23 e Å3
2069 reflectionsAbsolute structure: ?
239 parametersFlack parameter: ?
1 restraintRogers parameter: ?
Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.2787 (2)0.2053 (4)0.3279 (2)0.0354 (6)
H10.22000.13960.26920.042*
C20.2207 (2)0.3348 (5)0.3984 (2)0.0410 (7)
H20.27240.43470.43970.049*
C30.0963 (2)0.3897 (5)0.3702 (3)0.0481 (8)
C40.0687 (3)0.5894 (6)0.4046 (3)0.0631 (10)
H4A0.12650.62770.47240.076*
H4B0.00730.58880.42560.076*
C50.0673 (3)0.7374 (5)0.3081 (4)0.0659 (10)
H5A0.00140.71610.24720.079*
H5B0.06150.86550.33890.079*
C60.1748 (3)0.7262 (4)0.2578 (3)0.0525 (8)
H60.24860.71770.31530.063*
C70.1814 (3)0.6562 (4)0.1444 (3)0.0503 (8)
C80.2969 (3)0.5873 (5)0.1194 (3)0.0468 (7)
H80.29230.60640.03650.056*
C90.3194 (3)0.3721 (5)0.1433 (2)0.0419 (7)
H9A0.37580.32870.09930.050*
H9B0.24690.30330.11450.050*
C100.3649 (2)0.3155 (4)0.2708 (2)0.0323 (6)
H100.38660.43390.31510.039*
C110.4738 (2)0.1839 (4)0.2903 (2)0.0378 (6)
H110.47470.11130.21950.045*
C120.4563 (2)0.0491 (4)0.3832 (2)0.0439 (7)
C130.5891 (2)0.2916 (5)0.3277 (2)0.0455 (7)
H13A0.59190.34890.40300.055*
H13B0.65330.20060.33550.055*
C140.0086 (3)0.2978 (6)0.2748 (3)0.0673 (11)
H14A0.04120.18240.25010.101*
H14B0.01090.38540.21090.101*
H14C0.06090.26660.30240.101*
C150.0772 (3)0.5911 (7)0.0548 (3)0.0753 (11)
H15A0.00680.64190.07310.113*
H15B0.07370.45310.05400.113*
H15C0.08450.63680.02000.113*
C160.6476 (3)0.3626 (5)0.1469 (3)0.0481 (7)
H16A0.58930.27470.10480.058*
H16B0.71930.29080.17450.058*
C170.6915 (3)0.5830 (6)0.3049 (3)0.0568 (9)
H17A0.76440.51780.33740.068*
H17B0.66280.64220.36780.068*
C180.6700 (3)0.5208 (5)0.0673 (3)0.0610 (9)
H18A0.69830.46520.00310.073*
H18B0.59700.58700.03610.073*
C190.7136 (3)0.7371 (6)0.2215 (3)0.0697 (10)
H19A0.64190.80850.19340.084*
H19B0.77210.82630.26170.084*
N0.60588 (19)0.4434 (4)0.24620 (18)0.0419 (6)
O10.39115 (18)0.7008 (3)0.1779 (2)0.0641 (7)
H1A0.44950.63320.19730.096*
O20.1778 (3)0.8609 (4)0.1609 (3)0.0845 (9)
O30.14029 (17)0.2566 (4)0.46360 (19)0.0613 (7)
O40.34823 (15)0.0656 (3)0.40522 (16)0.0440 (5)
O50.5259 (2)0.0639 (4)0.4365 (2)0.0649 (7)
O60.7532 (2)0.6551 (4)0.1254 (2)0.0678 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0331 (13)0.0335 (14)0.0376 (14)0.0022 (11)0.0032 (10)0.0047 (12)
C20.0336 (13)0.0482 (17)0.0435 (16)0.0015 (12)0.0135 (12)0.0037 (14)
C30.0325 (14)0.0540 (19)0.0604 (19)0.0025 (14)0.0156 (13)0.0134 (17)
C40.0520 (19)0.073 (2)0.072 (2)0.0145 (18)0.0297 (17)0.003 (2)
C50.070 (2)0.0451 (19)0.089 (3)0.0156 (18)0.0315 (19)0.004 (2)
C60.0608 (18)0.0330 (17)0.064 (2)0.0023 (14)0.0126 (15)0.0011 (15)
C70.0543 (17)0.0281 (15)0.066 (2)0.0054 (13)0.0064 (15)0.0079 (14)
C80.0523 (17)0.0445 (17)0.0430 (16)0.0003 (14)0.0084 (13)0.0106 (14)
C90.0461 (15)0.0467 (16)0.0324 (14)0.0087 (13)0.0071 (12)0.0003 (13)
C100.0349 (13)0.0317 (14)0.0306 (13)0.0050 (11)0.0074 (10)0.0016 (11)
C110.0388 (14)0.0434 (16)0.0328 (14)0.0095 (12)0.0115 (11)0.0020 (12)
C120.0424 (15)0.0452 (17)0.0443 (16)0.0096 (14)0.0098 (13)0.0037 (14)
C130.0366 (14)0.065 (2)0.0364 (15)0.0050 (14)0.0110 (11)0.0041 (15)
C140.0379 (16)0.060 (2)0.096 (3)0.0009 (16)0.0017 (17)0.015 (2)
C150.058 (2)0.084 (3)0.071 (2)0.012 (2)0.0148 (17)0.008 (2)
C160.0527 (16)0.0531 (18)0.0422 (16)0.0025 (15)0.0182 (13)0.0040 (15)
C170.0459 (16)0.073 (2)0.0537 (18)0.0100 (17)0.0146 (14)0.0156 (19)
C180.071 (2)0.063 (2)0.0545 (19)0.0047 (18)0.0258 (17)0.0017 (18)
C190.066 (2)0.062 (2)0.083 (3)0.0115 (19)0.0228 (19)0.017 (2)
N0.0367 (12)0.0561 (15)0.0351 (12)0.0013 (11)0.0122 (10)0.0053 (12)
O10.0548 (13)0.0511 (14)0.0851 (17)0.0106 (11)0.0121 (12)0.0156 (13)
O20.114 (2)0.0458 (15)0.095 (2)0.0084 (15)0.0268 (18)0.0058 (15)
O30.0436 (11)0.0799 (17)0.0678 (14)0.0123 (11)0.0285 (10)0.0279 (14)
O40.0425 (11)0.0441 (11)0.0470 (11)0.0054 (9)0.0135 (9)0.0138 (9)
O50.0584 (13)0.0708 (17)0.0663 (14)0.0282 (13)0.0148 (11)0.0282 (13)
O60.0679 (14)0.0695 (16)0.0750 (15)0.0158 (13)0.0351 (12)0.0037 (14)
Geometric parameters (Å, °) top
C1—O41.458 (3)C11—C121.490 (4)
C1—C21.484 (4)C11—C131.523 (4)
C1—C101.530 (3)C11—H110.9800
C1—H10.9800C12—O51.208 (3)
C2—O31.441 (3)C12—O41.346 (3)
C2—C31.471 (4)C13—N1.470 (4)
C2—H20.9800C13—H13A0.9700
C3—O31.449 (4)C13—H13B0.9700
C3—C141.498 (5)C14—H14A0.9600
C3—C41.500 (5)C14—H14B0.9600
C4—C51.535 (5)C14—H14C0.9600
C4—H4A0.9700C15—H15A0.9600
C4—H4B0.9700C15—H15B0.9600
C5—C61.500 (5)C15—H15C0.9600
C5—H5A0.9700C16—N1.474 (4)
C5—H5B0.9700C16—C181.506 (5)
C6—C71.443 (5)C16—H16A0.9700
C6—O21.486 (4)C16—H16B0.9700
C6—H60.9800C17—N1.460 (4)
C7—O21.438 (4)C17—C191.514 (5)
C7—C151.505 (5)C17—H17A0.9700
C7—C81.518 (4)C17—H17B0.9700
C8—O11.411 (4)C18—O61.417 (4)
C8—C91.535 (4)C18—H18A0.9700
C8—H80.9800C18—H18B0.9700
C9—C101.540 (4)C19—O61.432 (4)
C9—H9A0.9700C19—H19A0.9700
C9—H9B0.9700C19—H19B0.9700
C10—C111.544 (3)O1—H1A0.8200
C10—H100.9800
O4—C1—C2108.2 (2)C12—C11—C13110.2 (2)
O4—C1—C10106.18 (18)C12—C11—C10104.2 (2)
C2—C1—C10111.4 (2)C13—C11—C10113.7 (2)
O4—C1—H1110.3C12—C11—H11109.5
C2—C1—H1110.3C13—C11—H11109.5
C10—C1—H1110.3C10—C11—H11109.5
O3—C2—C359.70 (17)O5—C12—O4120.6 (3)
O3—C2—C1119.8 (3)O5—C12—C11127.7 (3)
C3—C2—C1125.2 (3)O4—C12—C11111.6 (2)
O3—C2—H2113.8N—C13—C11113.2 (2)
C3—C2—H2113.8N—C13—H13A108.9
C1—C2—H2113.8C11—C13—H13A108.9
O3—C3—C259.13 (17)N—C13—H13B108.9
O3—C3—C14112.2 (3)C11—C13—H13B108.9
C2—C3—C14123.1 (3)H13A—C13—H13B107.7
O3—C3—C4116.5 (3)C3—C14—H14A109.5
C2—C3—C4115.9 (3)C3—C14—H14B109.5
C14—C3—C4116.5 (3)H14A—C14—H14B109.5
C3—C4—C5112.8 (3)C3—C14—H14C109.5
C3—C4—H4A109.0H14A—C14—H14C109.5
C5—C4—H4A109.0H14B—C14—H14C109.5
C3—C4—H4B109.0C7—C15—H15A109.5
C5—C4—H4B109.0C7—C15—H15B109.5
H4A—C4—H4B107.8H15A—C15—H15B109.5
C6—C5—C4112.5 (3)C7—C15—H15C109.5
C6—C5—H5A109.1H15A—C15—H15C109.5
C4—C5—H5A109.1H15B—C15—H15C109.5
C6—C5—H5B109.1N—C16—C18110.4 (3)
C4—C5—H5B109.1N—C16—H16A109.6
H5A—C5—H5B107.8C18—C16—H16A109.6
C7—C6—O258.8 (2)N—C16—H16B109.6
C7—C6—C5126.8 (3)C18—C16—H16B109.6
O2—C6—C5115.5 (3)H16A—C16—H16B108.1
C7—C6—H6114.4N—C17—C19110.8 (3)
O2—C6—H6114.4N—C17—H17A109.5
C5—C6—H6114.4C19—C17—H17A109.5
O2—C7—C662.1 (2)N—C17—H17B109.5
O2—C7—C15110.5 (3)C19—C17—H17B109.5
C6—C7—C15124.2 (3)H17A—C17—H17B108.1
O2—C7—C8113.0 (3)O6—C18—C16111.7 (3)
C6—C7—C8120.7 (3)O6—C18—H18A109.3
C15—C7—C8112.8 (3)C16—C18—H18A109.3
O1—C8—C7111.2 (3)O6—C18—H18B109.3
O1—C8—C9111.7 (2)C16—C18—H18B109.3
C7—C8—C9113.3 (3)H18A—C18—H18B107.9
O1—C8—H8106.7O6—C19—C17111.3 (3)
C7—C8—H8106.7O6—C19—H19A109.4
C9—C8—H8106.7C17—C19—H19A109.4
C8—C9—C10116.1 (2)O6—C19—H19B109.4
C8—C9—H9A108.3C17—C19—H19B109.4
C10—C9—H9A108.3H19A—C19—H19B108.0
C8—C9—H9B108.3C17—N—C13109.8 (2)
C10—C9—H9B108.3C17—N—C16108.9 (2)
H9A—C9—H9B107.4C13—N—C16111.1 (2)
C1—C10—C9115.9 (2)C8—O1—H1A109.5
C1—C10—C11103.6 (2)C7—O2—C659.1 (2)
C9—C10—C11113.6 (2)C2—O3—C361.17 (18)
C1—C10—H10107.8C12—O4—C1110.9 (2)
C9—C10—H10107.8C18—O6—C19110.1 (2)
C11—C10—H10107.8
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···N0.822.233.048 (3)178
C1—H1···O2i0.982.323.169 (4)145
C2—H2···O5ii0.982.503.260 (3)134
C4—H4B···O3iii0.972.523.367 (4)146
Symmetry codes: (i) x, y−1, z; (ii) −x+1, y+1/2, −z+1; (iii) −x, y+1/2, −z+1.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
O1—H1A···N0.822.233.048 (3)178
C1—H1···O2i0.982.323.169 (4)145
C2—H2···O5ii0.982.503.260 (3)134
C4—H4B···O3iii0.972.523.367 (4)146
Symmetry codes: (i) x, y−1, z; (ii) −x+1, y+1/2, −z+1; (iii) −x, y+1/2, −z+1.
Acknowledgements top

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

references
References top

Bruker, (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.

El Hassany, B., El Hanbali, F., Akssira, M., Mellouki, F., Haidou, A. & Barero, A. F. (2004). Fitoterapia, 75, 573–576.

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.

Hwang, D.-R., Wu, Y.-S., Chang, C.-W., Lien, T.-W., Chen, W.-C., Tan, U.-K., Hsu, J. T. A. & Hsieh, H.-P. (2006). Bioorg. Med. Chem. 14, 83—91.

Moumou, M., Akssira, M., El Ammari, L., Benharref, A. & Berraho, M. (2010). Acta Cryst. E66, o2395.

Neelakantan, S., Nasim, Sh., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346–4349.

Neukirch, H., Kaneider, N. C., Wiedermann, C. J., Guerriero, A. & D?Ambrosio, M. (2003). Bioorg. Med. Chem. 11, 1503–1510.

Qureshi, S., Ageel, A. M., Al-Yahya, M. A., Tariq, M., Mossa, J. S. & Shah, A. H. (1990). J. Ethnopharmacol. 28, 157–162.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.