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Mikanolide [systematic names: 1,10:2,3-di­epoxy-6,8-di­hy­droxy-11-vinyl­germacr-4-ene 12,14-di-γ-lactone and 7,10a-di­methyl-1a,1b,2a,6a,7,9a,10,10a-octa­hydro-4H-6,3-metheno­furo­[3,2-c]­bisoxireno­[f,h]­oxa­cyclo­undecin-4,8(6H)-dione], C15H14O6, derived from a variety of Mikania micrantha growing in Portland, Jamaica, contains a methyl­cyclo­decane ring fused to an unsaturated planar α,γ-lactone, an envelope-type near-planar vinyl-β,γ-lactone and two epoxide moieties. The crystal packing shows stacks of mikanolide mol­ecules interlocked via a network of non-classical C—H...O hydrogen bonds between the lactone units.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270104017809/bm1574sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270104017809/bm1574Isup2.hkl
Contains datablock I

CCDC reference: 257014

Comment top

Mikanolide, (I), is a sequiterpene dilactone isolated from a variety of Mikania species abundant in many regions. It is used locally as a folk medicine and has attracted the attention of natural products chemists because of its [AUTHOR: can these properties be tied to individual references?] anti-bacterial, antitumor, antimicrobial, cytotoxic and phytotoxic activities (Ahmed et al., 2001; Aguinaldo et al., 1995; Bohlmann et al., 1984; Facey et al., 1999; Gutierrez et al., 1985; Pickman, 1986; Valdes, 1998). Although structural studies of (I) and dihydromikanolide, (II), [1,10:2,3-diepoxy-6,8-dihydroxygermacr-4-ene-12,14- di-γ-lactone, C15H16O6] from Mikania scandens (L.) Willd have been published by Herz et al. (1970) and the crystal structure of (II) has been reported (Cox & Sim 1974), to our knowledge the solid-state structure of (I) has never been investigated. As part of an effort to explore structure–activity relationships of natural products isolated from medicinal plants that are used as alternative medicine in Jamaican society, we report here the structure of mikanolide isolated from Mikania micrantha from Port Antonio, [AUTHOR: It says "Portland" in the Abstract: please clarify.] Jamaica, and compare the results with those reported for dihydromikanolide from Mikania scandens (L.) Willd.

A displacement ellipsoid plot of (I) (Fig. 1) shows a methyl-substituted cyclodecane ring fused to a planar unsaturated α,γ-lactone, a nearly planar envelope-type vinyl β,γ-lactone and two epoxides. The conformations of the cyclodecane ring and epoxide units in (I) are very similar to those reported in the dihydromikanolide isolated from Mikania scandens (L.) Willd (Cox & Sim, 1974), although subtle differences were noted. These are evident in the appearance on the same face of the macrocycle of a methyl group (C15) attached to atoms C10 and C14 of the α,γ-lactone, and in the bond distances, valence angles and endocyclic torsion angles of the cyclododecane ring, which are comparable to the corresponding angles in dihydromikanolide (see Table 1). The same is true of both epoxides at C1—C10 and C2—C3 and the near planar α-γ-lactone at C4—C5—C6. The dihedral angle between the epoxide rings is nearly identical for the two compounds, its value being 36.1 (4)° in (I) and 34.4 (7)° in (II). An exception is the endocyclic C5—C6—C7—C8 torsion angle, which has a value of 10.2 (4)° in the case of (I) and −2.0 (2)° in (II). Although the C4C5 double bond of the α,γ-lactone in (I) shows the same strain as that in (II), slight variations in the conformations of the α,γ-lactones in (I) and (II) were noted, as apparent from the torsion angles around the α,γ-lactone rings. For example, in (I), the C14—O3—C6—C5 and C3–C4—C14—O2 torsion angles take values of 6.3 (3) and −10.7 (6)°, respectively, while in (II), these values are 2.0 (7) and −17.0 (7)°. The major structural and conformational differences between (I) and (II) occur in the β,γ-trans-fused γ-lactone at C7—C8, which has a more planar five-membered lactone ring in (I), with endocyclic torsion angles approximately half the values of those in the saturated γ-lactone of dihydromikanolide. In (I), torsion angles of 35.7 (6), −172.4 (4) and 7.1 (7)° were observed for C6—C7—C11—C13, C13—C11—C12—O5 and C13—C11—C12—O4, respectively, while corresponding values of 77.0 (7), 148.0 (7) and −34.0 (7)° have been reported for dihydromikanolide.

Molecules of (I) are stacked along the b axis; they are linked by a network of C—H···O hydrogen bonds between the lactone units of neighbouring molecules related by a 21 screw axis (see Table 2 and Fig. 2). The geometric parameters for these non-classical hydrogen bonds are normal and similar to those reported for a variety of compounds containing such bonds, for example, in diospyrin [1',5-dihydroxy-3',7-dimethyl-2,2'-binaphthalene-1,4,5',8'-tetrone C22H14O6, see diagram 3] (Harrison & Musgrave, 2004). ##AUTHOR: Please check the changes in wording abve.

In conclusion, the structural determination of (I) is the first for an unsaturated mikanolide and reveals a near-planar β-lactone unit that may allow for intercalation of mikanolide into the minor groove of DNA, a feature that provides a possible explanation for its biological activity. In view of the use of folk medicinal plants as a guide to the development of new pharmaceuticals, studies are currently in progress in our laboratories to explore the structure–activity relationship of natural products isolated from a variety of common native Jamaican plants.

Experimental top

Mikanolide extracted from Mikania micrantha Kunth (from Portland, Jamaica) was isolated as described by Facey et al. (1999). Crystals were obtained when an extract in hexane–ethyl acetate (1:3) was allowed to stand at room temperature for several days.

Refinement top

##AUTHOR: ## Was the hand (enantiomer) chosen at random, because the ## absolute structure is not known, or was there evidence from other ## sources as to which hand is adopted by (1)?

All H atoms were assigned by assuming idealized geometry, C—H distances of 0.98, 0.96, 0.97 and 0.93 Å for tertiary CH, methyl CH3, secondary CH2 and terminal CH2 atoms, respectively, and with Uiso(H) values of 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for all other H atoms. ##AUTHOR: Please check the change above.

Computing details top

Data collection: XSCANS (Bruker, 1997); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. A view of the packing in (I), showing stacks of molecules running along the b axis. C—H···O hydrogen bonds are shown as dashed lines. ##AUTHOR: Please check the wording above. ##AUTHOR: Please check the new version of Figure 2.
7,10a-dimethyl-1a,1 b,2a,6a,7,9a,10,10a-octahydro-4H-6,3- methenofuro[3,2-c]bisoxireno[f,h]oxacycloundecin-4,8(6H)-dione or 1,10:2,3-diepoxy-6,8-dihydroxygermacr-4-ene-11-vinyl-12,14- di-γ-lactone top
Crystal data top
C15H14O6F(000) = 304
Mr = 290.26Dx = 1.452 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 8.9090 (12) ÅCell parameters from 43 reflections
b = 7.1840 (8) Åθ = 9.5–24.3°
c = 10.4940 (11) ŵ = 0.11 mm1
β = 98.830 (9)°T = 293 K
V = 663.60 (14) Å3Rectangular prism, colourless
Z = 20.4 × 0.3 × 0.2 mm
Data collection top
Bruker P4
diffractometer
Rint = 0.028
Radiation source: fine-focus sealed tubeθmax = 25.0°, θmin = 2.0°
Graphite monochromatorh = 101
2θ/ω scansk = 81
1782 measured reflectionsl = 1212
1483 independent reflections3 standard reflections every 97 reflections
1269 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.037 w = 1/[σ2(Fo2) + (0.049P)2 + 0.069P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.098(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.13 e Å3
1483 reflectionsΔρmin = 0.11 e Å3
191 parametersExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.028 (6)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Secondary atom site location: difference Fourier mapAbsolute structure parameter: not reliably determined
Crystal data top
C15H14O6V = 663.60 (14) Å3
Mr = 290.26Z = 2
Monoclinic, P21Mo Kα radiation
a = 8.9090 (12) ŵ = 0.11 mm1
b = 7.1840 (8) ÅT = 293 K
c = 10.4940 (11) Å0.4 × 0.3 × 0.2 mm
β = 98.830 (9)°
Data collection top
Bruker P4
diffractometer
Rint = 0.028
1782 measured reflections3 standard reflections every 97 reflections
1483 independent reflections intensity decay: none
1269 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.098Δρmax = 0.13 e Å3
S = 1.04Δρmin = 0.11 e Å3
1483 reflectionsAbsolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
191 parametersAbsolute structure parameter: not reliably determined
1 restraint
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.5920 (3)0.0333 (4)0.4209 (2)0.0852 (10)
O20.3885 (3)0.5396 (5)0.2236 (2)0.0851 (10)
O30.5364 (2)0.4654 (4)0.07723 (18)0.0692 (9)
O41.1290 (3)0.3778 (4)0.0908 (3)0.0934 (11)
O51.0709 (2)0.3466 (4)0.1070 (2)0.0720 (9)
O60.9159 (3)0.3606 (5)0.51889 (19)0.0823 (9)
C10.8165 (4)0.2399 (6)0.4363 (3)0.0636 (11)
C20.6632 (4)0.2007 (6)0.4739 (3)0.0686 (13)
C30.5248 (4)0.2058 (5)0.3769 (3)0.0624 (11)
C40.5427 (3)0.2613 (5)0.2457 (3)0.0512 (10)
C50.6328 (3)0.1907 (5)0.1694 (3)0.0534 (9)
C60.6465 (3)0.3220 (5)0.0634 (3)0.0583 (10)
C70.8046 (3)0.4124 (5)0.0706 (2)0.0494 (9)
C80.9358 (3)0.3340 (5)0.1703 (3)0.0526 (10)
C90.9779 (3)0.4304 (6)0.2996 (3)0.0628 (10)
C100.8584 (3)0.4230 (5)0.3877 (2)0.0551 (10)
C110.8706 (4)0.4031 (5)0.0531 (3)0.0592 (11)
C121.0341 (4)0.3768 (5)0.0215 (4)0.0681 (11)
C130.8000 (5)0.4149 (7)0.1742 (3)0.0855 (15)
C140.4773 (3)0.4340 (6)0.1874 (3)0.0602 (12)
C150.7570 (4)0.5868 (5)0.3851 (3)0.0647 (11)
H10.865900.132600.402600.0930*
H20.650900.230900.562800.1090*
H30.429600.240200.406900.0920*
H50.680700.075500.180600.0810*
H60.619100.259100.019800.0850*
H70.793400.544400.090900.0810*
H80.915300.202500.185600.0750*
H9A0.999900.559900.284000.0730*
H9B1.070300.374400.344100.0730*
H13A0.855500.406300.242200.1350*
H13B0.695400.431700.190900.1350*
H15A0.686100.567600.444100.0930*
H15B0.702600.603100.299500.0930*
H15C0.816600.695900.409900.0930*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.115 (2)0.0651 (18)0.0830 (16)0.0083 (17)0.0395 (15)0.0212 (16)
O20.0606 (14)0.106 (2)0.0894 (17)0.0246 (17)0.0137 (13)0.0044 (19)
O30.0562 (12)0.098 (2)0.0520 (11)0.0065 (14)0.0041 (9)0.0165 (13)
O40.1121 (19)0.0646 (18)0.125 (2)0.0031 (16)0.0869 (18)0.0127 (16)
O50.0621 (13)0.0731 (17)0.0885 (16)0.0009 (13)0.0363 (11)0.0103 (14)
O60.0795 (14)0.116 (2)0.0458 (11)0.0012 (16)0.0082 (10)0.0142 (15)
C10.073 (2)0.069 (2)0.0475 (16)0.0109 (19)0.0049 (14)0.0140 (17)
C20.089 (2)0.070 (3)0.0524 (17)0.003 (2)0.0283 (16)0.0133 (18)
C30.0711 (19)0.065 (2)0.0565 (17)0.0052 (18)0.0272 (15)0.0043 (17)
C40.0476 (15)0.062 (2)0.0459 (14)0.0080 (16)0.0133 (12)0.0036 (15)
C50.0615 (16)0.0476 (17)0.0549 (15)0.0149 (15)0.0211 (13)0.0087 (15)
C60.0659 (18)0.070 (2)0.0416 (14)0.0126 (18)0.0163 (13)0.0134 (16)
C70.0605 (15)0.0438 (16)0.0471 (14)0.0062 (15)0.0189 (12)0.0037 (14)
C80.0541 (16)0.0481 (17)0.0610 (17)0.0019 (15)0.0262 (13)0.0015 (15)
C90.0528 (15)0.076 (2)0.0583 (16)0.0081 (19)0.0048 (13)0.0008 (18)
C100.0567 (16)0.068 (2)0.0376 (13)0.0000 (17)0.0024 (12)0.0034 (15)
C110.083 (2)0.0457 (18)0.0569 (17)0.0101 (18)0.0358 (15)0.0060 (16)
C120.092 (2)0.0382 (18)0.086 (2)0.0039 (17)0.0514 (19)0.0021 (17)
C130.118 (3)0.091 (3)0.0557 (18)0.017 (3)0.0398 (19)0.001 (2)
C140.0450 (14)0.083 (3)0.0518 (15)0.0008 (19)0.0052 (12)0.0036 (18)
C150.073 (2)0.061 (2)0.0589 (18)0.0047 (18)0.0063 (16)0.0175 (17)
Geometric parameters (Å, º) top
O1—C21.432 (5)C8—C91.518 (5)
O1—C31.422 (5)C9—C101.514 (4)
O2—C141.199 (5)C10—C151.481 (5)
O3—C61.445 (4)C11—C121.456 (5)
O3—C141.361 (4)C11—C131.331 (5)
O4—C121.197 (5)C1—H10.9802
O5—C81.464 (3)C2—H20.9802
O5—C121.355 (5)C3—H30.9806
O6—C11.432 (5)C5—H50.9303
O6—C101.464 (3)C6—H60.9801
C1—C21.505 (5)C7—H70.9804
C1—C101.479 (5)C8—H80.9801
C2—C31.474 (5)C9—H9A0.9698
C3—C41.465 (4)C9—H9B0.9693
C4—C51.319 (4)C13—H13A0.9305
C4—C141.464 (5)C13—H13B0.9293
C5—C61.478 (5)C15—H15A0.9599
C6—C71.542 (4)C15—H15B0.9601
C7—C81.550 (4)C15—H15C0.9600
C7—C111.507 (4)
C2—O1—C362.2 (2)O5—C12—C11109.2 (3)
C6—O3—C14108.9 (3)O2—C14—O3121.6 (4)
C8—O5—C12111.8 (2)O2—C14—C4130.0 (3)
C1—O6—C1061.4 (2)O3—C14—C4108.3 (3)
O6—C1—C2117.1 (3)O6—C1—H1115.10
O6—C1—C1060.3 (2)C2—C1—H1115.03
C2—C1—C10123.0 (3)C10—C1—H1115.08
O1—C2—C1114.9 (3)O1—C2—H2116.62
O1—C2—C358.6 (2)C1—C2—H2116.52
C1—C2—C3120.7 (3)C3—C2—H2116.61
O1—C3—C259.2 (2)O1—C3—H3117.20
O1—C3—C4116.2 (3)C2—C3—H3117.23
C2—C3—C4117.1 (3)C4—C3—H3117.21
C3—C4—C5129.0 (3)C4—C5—H5125.13
C3—C4—C14122.0 (3)C6—C5—H5125.01
C5—C4—C14108.2 (3)O3—C6—H6109.76
C4—C5—C6109.9 (3)C5—C6—H6109.77
O3—C6—C5104.1 (2)C7—C6—H6109.78
O3—C6—C7108.9 (3)C6—C7—H7107.18
C5—C6—C7114.4 (2)C8—C7—H7107.23
C6—C7—C8117.9 (3)C11—C7—H7107.24
C6—C7—C11114.4 (2)O5—C8—H8108.71
C8—C7—C11102.2 (2)C7—C8—H8108.70
O5—C8—C7105.0 (2)C9—C8—H8108.66
O5—C8—C9105.7 (2)C8—C9—H9A108.38
C7—C8—C9119.7 (3)C8—C9—H9B108.44
C8—C9—C10115.4 (2)C10—C9—H9A108.42
O6—C10—C158.3 (2)C10—C9—H9B108.42
O6—C10—C9114.1 (2)H9A—C9—H9B107.50
O6—C10—C15112.7 (2)C11—C13—H13A119.93
C1—C10—C9118.7 (3)C11—C13—H13B120.10
C1—C10—C15121.8 (3)H13A—C13—H13B119.97
C9—C10—C15116.4 (3)C10—C15—H15A109.50
C7—C11—C12108.6 (3)C10—C15—H15B109.45
C7—C11—C13129.1 (3)C10—C15—H15C109.47
C12—C11—C13122.4 (3)H15A—C15—H15B109.47
O4—C12—O5121.3 (3)H15A—C15—H15C109.50
O4—C12—C11129.5 (4)H15B—C15—H15C109.44
C3—O1—C2—C1112.1 (3)C3—C4—C14—O3168.4 (3)
C2—O1—C3—C4107.3 (3)C3—C4—C5—C6163.5 (3)
C14—O3—C6—C56.3 (3)C5—C4—C14—O2178.7 (4)
C14—O3—C6—C7116.0 (3)C5—C4—C14—O32.2 (4)
C6—O3—C14—O2176.3 (3)C14—C4—C5—C66.3 (4)
C6—O3—C14—C42.9 (3)C3—C4—C14—O210.7 (6)
C12—O5—C8—C714.7 (4)C4—C5—C6—O37.9 (3)
C12—O5—C8—C9142.0 (3)C4—C5—C6—C7110.8 (3)
C8—O5—C12—O4174.6 (3)O3—C6—C7—C8126.1 (3)
C8—O5—C12—C114.9 (4)O3—C6—C7—C11113.6 (3)
C10—O6—C1—C2114.3 (4)C5—C6—C7—C11130.4 (3)
C1—O6—C10—C9110.0 (3)C5—C6—C7—C810.2 (4)
C1—O6—C10—C15114.4 (3)C6—C7—C8—C997.7 (4)
O6—C1—C10—C1598.6 (3)C6—C7—C8—O5144.1 (3)
C2—C1—C10—O6104.9 (3)C8—C7—C11—C13164.3 (4)
O6—C1—C10—C9102.0 (3)C11—C7—C8—C9135.9 (3)
C2—C1—C10—C156.3 (4)C6—C7—C11—C12144.1 (3)
O6—C1—C2—C3135.3 (4)C11—C7—C8—O517.6 (3)
C10—C1—C2—O1131.5 (3)C8—C7—C11—C1215.4 (4)
C10—C1—C2—C364.6 (5)C6—C7—C11—C1335.7 (6)
O6—C1—C2—O1157.8 (3)C7—C8—C9—C1066.3 (4)
C2—C1—C10—C9153.1 (3)O5—C8—C9—C10175.8 (3)
O1—C2—C3—C4105.8 (3)C8—C9—C10—C164.3 (4)
C1—C2—C3—C43.6 (5)C8—C9—C10—C1596.3 (4)
C1—C2—C3—O1102.2 (4)C8—C9—C10—O6129.9 (3)
O1—C3—C4—C14179.0 (3)C13—C11—C12—O47.1 (7)
O1—C3—C4—C512.4 (5)C13—C11—C12—O5172.4 (4)
C2—C3—C4—C554.7 (5)C7—C11—C12—O4173.2 (4)
C2—C3—C4—C14113.9 (4)C7—C11—C12—O57.4 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H5···O4i0.932.503.282 (4)141
C7—H7···O4ii0.982.493.396 (4)153
C8—H8···O4i0.982.543.409 (4)147
Symmetry codes: (i) x+2, y1/2, z; (ii) x+2, y+1/2, z.

Experimental details

Crystal data
Chemical formulaC15H14O6
Mr290.26
Crystal system, space groupMonoclinic, P21
Temperature (K)293
a, b, c (Å)8.9090 (12), 7.1840 (8), 10.4940 (11)
β (°) 98.830 (9)
V3)663.60 (14)
Z2
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.4 × 0.3 × 0.2
Data collection
DiffractometerBruker P4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
1782, 1483, 1269
Rint0.028
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.098, 1.04
No. of reflections1483
No. of parameters191
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.13, 0.11
Absolute structureFlack H D (1983), Acta Cryst. A39, 876-881
Absolute structure parameternot reliably determined

Computer programs: XSCANS (Bruker, 1997), XSCANS, SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997) and PLATON (Spek, 2003), SHELXTL.

Selected torsion angles (º) top
C14—O3—C6—C56.3 (3)C6—C7—C11—C1335.7 (6)
C3—C4—C14—O210.7 (6)C13—C11—C12—O47.1 (7)
C5—C6—C7—C810.2 (4)C13—C11—C12—O5172.4 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H5···O4i0.932.503.282 (4)141
C7—H7···O4ii0.982.493.396 (4)153
C8—H8···O4i0.982.543.409 (4)147
Symmetry codes: (i) x+2, y1/2, z; (ii) x+2, y+1/2, z.
 

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