Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Previous article
Next article
Previous article
Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Next article

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 12| December 2011| Page o3470
https://doi.org/10.1107/S1600536811048938

De­hydro­leucodin: a guaiane-type sesquiterpene lactone

Horacio A. Priestap,a Khalil A. Abboud,b Alvaro E. Velandia,a Luis A. Lopezc and Manuel A. Barbieria*

aDepartment of Biological Sciences, Florida International University, Miami, FL 33199, USA, bDepartment of Chemistry, University of Florida, PO Box 117200 Gainesville, Gainesville, FL 32611-7200, USA, and cLaboratory of Cytoskeleton and Cell Cycle, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, 5500 Mendoza, Argentina
*Correspondence e-mail: barbieri@fiu.edu

(Received 9 November 2011; accepted 16 November 2011; online 30 November 2011)

Dehydro­leucodin [systematic name: (1S,6S,2R)-9,13-dimeth­yl-5-methyl­ene-3-oxatricyclo­[8.3.0.02,6]trideca-9,12-diene-4,11-dione], C15H16O3, is a guanolide isolated from Artemisia douglasiana. The fused-ring system contains a seven-membered ring that adopts a chair conformation, a fused planar cyclo­pentenone ring and a five-membered lactone ring fused in envelope conformation. The absolute structure determined by X-ray analysis agrees with that previously assigned to this compound by NMR studies [Bohlmann & Zdero (1972[Bohlmann, F. & Zdero, C. (1972). Tetrahedron Lett. 13, 621-624.]). Tetra­hedron Lett. 13, 621–624] and also with that of leucodine, a closely related guaianolide [Martinez et al. (1988[Martinez, M. V., Munoz-Zamora, A. & Joseph-Nathan, P. (1988). J. Nat. Prod. 51, 221-228.]). J. Nat. Prod. 51, 221–228].

Related literature

For NMR studies of dehydro­leucodin and leucodine, see: Bohlmann & Zdero (1972[Bohlmann, F. & Zdero, C. (1972). Tetrahedron Lett. 13, 621-624.]); Martinez et al., (1988[Martinez, M. V., Munoz-Zamora, A. & Joseph-Nathan, P. (1988). J. Nat. Prod. 51, 221-228.]). For the pharmacological activity of dehydro­leucodin and related compounds, see Giordano et al. (1992[Giordano, O. S., Pestchanker, J. M., Guerreiro, E., Saad, J. R., Enriz, R. D., Rodriguez, A. M., Jauregui, E. A., Maria, A. O. M. & Wendel, G. H. (1992). J. Med. Chem. 35, 2452-2458.]).

[Scheme 1]

Experimental

Crystal data

  • C15H16O3

  • Mr = 244.28

  • Orthorhombic, P 21 21 21

  • a = 7.5101 (3) Å

  • b = 11.1065 (4) Å

  • c = 15.0228 (6) Å

  • V = 1253.07 (8) Å3

  • Z = 4

  • Cu Kα radiation

  • μ = 0.73 mm−1

  • T = 100 K

  • 0.29 × 0.07 × 0.05 mm
Data collection

  • Bruker APEXII DUO diffractometer

  • Absorption correction: integration (SADABS; Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.820, Tmax = 0.962

  • 10896 measured reflections

  • 2166 independent reflections

  • 2150 reflections with I > 2σ(I)

  • Rint = 0.064
Refinement

  • R[F2 > 2σ(F2)] = 0.027

  • wR(F2) = 0.068

  • S = 1.05

  • 2166 reflections

  • 165 parameters

  • H-atom parameters constrained

  • Δρmax = 0.19 e Å−3

  • Δρmin = −0.14 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 879 Friedel pairs

  • Flack parameter: 0.00 (17)

Data collection: APEX2 (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536811048938/bg2432sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811048938/bg2432Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811048938/bg2432Isup3.mol

Supporting information file. DOI: https://doi.org/10.1107/S1600536811048938/bg2432Isup4.cml

checkCIF report


Comment top

The title compound, a guaiane-type sesquiterpene lactone, was isolated from Artemisia douglasiana Bess (Asteraceae). NMR studies have been reported previously (Bohlmann & Zdero, 1972). By using a lanthanide shift reagent [Eu(fod)3] the lower field signals of dehydroleucodin could be resolved and showed the 5S, 6R and 7S configurations at the chiral centers. Here we report the crystal structure of dehydroleucodin that resulted coherent with the absolute stereochemistry previously reported by Bohlmann and Zdero (1972). The molecular geometry of dehydroleucodin is illustrated in Fig. 1. Inspection of the crystal structure shows that the cyclopentenone carbons, C-9 and C-10 are almost coplanar. The seven-membered ring adopts approximately a chair conformation with the atoms C-6, C-7, and C-8 above the plane. The lactone ring shows a half-chair conformation. H-5 and H-7 are located below the plane (beta-orientation) whereas H-6 is above the plane (beta-orientation), hence the configurations at the chiral centers 5, 6 and 7, is confirmed as being S, R and S, respectively. Bond distances and bond angles are normal.

Related literature top

For NMR studies of dehydroleucodin and leucodine, see: Bohlmann & Zdero (1972); Martinez et al., (1988). For the pharmacological activity of dehydroleucodin and related compounds, see Giordano et al. (1992).

Experimental top

Aerial parts of Artemisia douglasiana were collected in San Carlos, Mendoza (Argentina). The dried crushed plant material (10 g, dry weight) was exhaustedly extracted with boiling CHCl3. The CHCl3 extract was chromatographed on silica gel and alumina columns using mixtures of ethyl acetate and chloroform as eluants to give white crystals of dehydroleucodin (70 mg). This compound was identified by comparing the spectroscopic data with the previously published data (Bohlmann and Zdero, 1972). Crystals suitable for X-ray analysis were obtained by recrystallization from DMSO-water at 277K.

Refinement top

All the H atoms were placed in idealized positions and refined riding on their parent atoms, with C—H = 0.93-0.99 Å and Uiso(H) =1.5Ueq(C) for the methyl H atoms and 1.2Ueq(C) for the remaining ones. The Flack x parameter is 0.00 (17) confirming that the correct enantiomer is being reported.

Structure description top

The title compound, a guaiane-type sesquiterpene lactone, was isolated from Artemisia douglasiana Bess (Asteraceae). NMR studies have been reported previously (Bohlmann & Zdero, 1972). By using a lanthanide shift reagent [Eu(fod)3] the lower field signals of dehydroleucodin could be resolved and showed the 5S, 6R and 7S configurations at the chiral centers. Here we report the crystal structure of dehydroleucodin that resulted coherent with the absolute stereochemistry previously reported by Bohlmann and Zdero (1972). The molecular geometry of dehydroleucodin is illustrated in Fig. 1. Inspection of the crystal structure shows that the cyclopentenone carbons, C-9 and C-10 are almost coplanar. The seven-membered ring adopts approximately a chair conformation with the atoms C-6, C-7, and C-8 above the plane. The lactone ring shows a half-chair conformation. H-5 and H-7 are located below the plane (beta-orientation) whereas H-6 is above the plane (beta-orientation), hence the configurations at the chiral centers 5, 6 and 7, is confirmed as being S, R and S, respectively. Bond distances and bond angles are normal.

For NMR studies of dehydroleucodin and leucodine, see: Bohlmann & Zdero (1972); Martinez et al., (1988). For the pharmacological activity of dehydroleucodin and related compounds, see Giordano et al. (1992).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title molecule, showing 50% probability displacement ellipsoids.
(1S,6S,2R)-9,13-dimethyl-5-methylene-3- oxatricyclo[8.3.0.02,6]trideca-9,12-diene-4,11-dione top
Crystal data top
C15H16O3Dehydroleucodin
Mr = 244.28Dx = 1.295 Mg m−3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2abCell parameters from 9973 reflections
a = 7.5101 (3) Åθ = 2.9–67.8°
b = 11.1065 (4) ŵ = 0.73 mm−1
c = 15.0228 (6) ÅT = 100 K
V = 1253.07 (8) Å3Needles, colourless
Z = 40.29 × 0.07 × 0.05 mm
F(000) = 520
Data collection top
Bruker APEXII DUO
diffractometer		2166 independent reflections
Radiation source: IµS microsource2150 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.064
phi and ω scansθmax = 66.4°, θmin = 5.0°
Absorption correction: integration
(SADABS; Bruker, 2008)		h = −8→7
Tmin = 0.820, Tmax = 0.962k = −13→12
10896 measured reflectionsl = −17→17
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)] = 0.027H-atom parameters constrained
wR(F2) = 0.068 w = 1/[σ2(Fo2) + (0.0273P)2 + 0.2735P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2166 reflectionsΔρmax = 0.19 e Å−3
165 parametersΔρmin = −0.14 e Å−3
0 restraintsAbsolute structure: Flack (1983), 879 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.00 (17)
Crystal data top
C15H16O3V = 1253.07 (8) Å3
Mr = 244.28Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 7.5101 (3) ŵ = 0.73 mm−1
b = 11.1065 (4) ÅT = 100 K
c = 15.0228 (6) Å0.29 × 0.07 × 0.05 mm
Data collection top
Bruker APEXII DUO
diffractometer		2166 independent reflections
Absorption correction: integration
(SADABS; Bruker, 2008)		2150 reflections with I > 2σ(I)
Tmin = 0.820, Tmax = 0.962Rint = 0.064
10896 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.027H-atom parameters constrained
wR(F2) = 0.068Δρmax = 0.19 e Å−3
S = 1.05Δρmin = −0.14 e Å−3
2166 reflectionsAbsolute structure: Flack (1983), 879 Friedel pairs
165 parametersAbsolute structure parameter: 0.00 (17)
0 restraints
Special details top

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

Refinement. All H atoms were positioned geometrically (C—H=0.93/1.00 Å) and allowed to ride with Uiso(H)=1.2/1.5Ueq(C). Methyl ones were allowed to rotate around the corresponding C—C. The Flack x parameter is 0.00 (17) confirming that the correct enantiomer is refined for this structure.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.81504 (13)−0.02962 (8)0.26751 (7)0.0312 (2)
O20.80476 (13)0.43297 (8)0.09948 (6)0.0248 (2)
O30.87294 (16)0.62331 (10)0.06281 (7)0.0411 (3)
C10.68912 (15)0.17287 (10)0.25112 (8)0.0192 (3)
C20.77553 (16)0.05869 (11)0.22172 (10)0.0240 (3)
C30.79958 (18)0.06797 (12)0.12543 (10)0.0278 (3)
H3A0.85260.00720.08970.033*
C40.73794 (16)0.17220 (12)0.09389 (9)0.0241 (3)
C50.66907 (16)0.25183 (10)0.16885 (8)0.0192 (3)
H5A0.54060.27120.15880.023*
C60.77492 (16)0.36796 (10)0.18300 (8)0.0183 (3)
H6A0.89260.34780.21040.022*
C70.68007 (16)0.46068 (10)0.24137 (8)0.0190 (3)
H7A0.55480.46620.21910.023*
C80.66895 (18)0.43149 (11)0.33978 (8)0.0227 (3)
H8A0.61970.50150.37230.027*
H8B0.78990.41540.36310.027*
C90.55009 (17)0.32097 (11)0.35585 (8)0.0224 (3)
H9A0.51270.32020.41900.027*
H9B0.44140.32860.31900.027*
C100.63981 (17)0.20247 (11)0.33441 (9)0.0209 (3)
C110.77282 (17)0.57383 (11)0.21226 (9)0.0215 (3)
C120.82427 (19)0.55285 (12)0.11838 (9)0.0269 (3)
C130.80965 (17)0.67457 (11)0.25533 (10)0.0266 (3)
H13A0.87190.73760.22600.032*
H13B0.77390.68390.31560.032*
C140.7232 (2)0.20714 (14)−0.00173 (9)0.0321 (3)
H14A0.78340.1469−0.03870.048*
H14B0.77920.2859−0.01070.048*
H14C0.59730.2116−0.01860.048*
C150.6668 (2)0.12277 (12)0.41396 (9)0.0304 (3)
H15A0.55080.09770.43740.046*
H15B0.73190.16710.46000.046*
H15C0.73530.05150.39640.046*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0261 (5)0.0160 (4)0.0516 (6)0.0001 (4)−0.0029 (4)0.0034 (4)
O20.0299 (5)0.0231 (4)0.0214 (4)−0.0035 (4)0.0023 (4)0.0021 (4)
O30.0564 (7)0.0322 (6)0.0347 (6)−0.0113 (5)0.0045 (5)0.0112 (5)
C10.0158 (6)0.0158 (5)0.0261 (6)−0.0017 (5)−0.0029 (5)0.0001 (5)
C20.0158 (6)0.0161 (6)0.0401 (8)−0.0039 (5)−0.0027 (5)−0.0029 (5)
C30.0244 (7)0.0213 (6)0.0377 (8)−0.0010 (6)0.0033 (6)−0.0118 (6)
C40.0191 (6)0.0257 (6)0.0275 (7)−0.0051 (5)0.0011 (5)−0.0076 (6)
C50.0169 (6)0.0182 (6)0.0225 (6)−0.0011 (5)−0.0013 (5)−0.0027 (5)
C60.0186 (6)0.0176 (6)0.0186 (6)−0.0002 (5)−0.0010 (5)0.0015 (5)
C70.0179 (6)0.0156 (5)0.0236 (6)0.0019 (5)−0.0008 (5)−0.0001 (5)
C80.0275 (7)0.0179 (6)0.0227 (7)0.0003 (5)−0.0003 (5)−0.0032 (5)
C90.0259 (6)0.0215 (6)0.0198 (6)−0.0015 (6)0.0017 (5)−0.0022 (5)
C100.0193 (6)0.0181 (6)0.0253 (6)−0.0041 (5)−0.0037 (5)0.0014 (5)
C110.0176 (6)0.0179 (6)0.0289 (7)0.0018 (5)−0.0032 (5)0.0037 (5)
C120.0277 (7)0.0223 (6)0.0305 (7)−0.0047 (6)−0.0033 (6)0.0050 (5)
C130.0219 (6)0.0190 (6)0.0389 (7)0.0007 (5)−0.0039 (6)0.0003 (6)
C140.0315 (8)0.0399 (8)0.0251 (7)−0.0044 (6)0.0018 (6)−0.0099 (6)
C150.0371 (8)0.0252 (6)0.0288 (7)−0.0026 (6)−0.0048 (6)0.0075 (6)
Geometric parameters (Å, º) top
O1—C21.2343 (17)C7—H7A1.0000
O2—C121.3692 (16)C8—C91.5369 (17)
O2—C61.4649 (14)C8—H8A0.9900
O3—C121.2012 (17)C8—H8B0.9900
C1—C101.3456 (19)C9—C101.5132 (17)
C1—C21.4914 (16)C9—H9A0.9900
C1—C51.5230 (17)C9—H9B0.9900
C2—C31.461 (2)C10—C151.5009 (18)
C3—C41.334 (2)C11—C131.3218 (18)
C3—H3A0.9500C11—C121.4808 (19)
C4—C141.4920 (19)C13—H13A0.9500
C4—C51.5225 (17)C13—H13B0.9500
C5—C61.5299 (16)C14—H14A0.9800
C5—H5A1.0000C14—H14B0.9800
C6—C71.5286 (17)C14—H14C0.9800
C6—H6A1.0000C15—H15A0.9800
C7—C111.5019 (16)C15—H15B0.9800
C7—C81.5158 (17)C15—H15C0.9800
C12—O2—C6108.55 (9)C7—C8—H8B109.5
C10—C1—C2127.08 (12)C9—C8—H8B109.5
C10—C1—C5125.92 (11)H8A—C8—H8B108.1
C2—C1—C5107.0 (1)C10—C9—C8113.74 (10)
O1—C2—C3125.31 (13)C10—C9—H9A108.8
O1—C2—C1127.97 (13)C8—C9—H9A108.8
C3—C2—C1106.68 (11)C10—C9—H9B108.8
C4—C3—C2111.72 (12)C8—C9—H9B108.8
C4—C3—H3A124.1H9A—C9—H9B107.7
C2—C3—H3A124.1C1—C10—C15123.99 (12)
C3—C4—C14126.41 (12)C1—C10—C9122.21 (11)
C3—C4—C5111.05 (12)C15—C10—C9113.80 (11)
C14—C4—C5122.40 (12)C13—C11—C12123.01 (12)
C4—C5—C1103.43 (10)C13—C11—C7131.52 (13)
C4—C5—C6114.58 (10)C12—C11—C7105.47 (10)
C1—C5—C6108.75 (9)O3—C12—O2121.46 (13)
C4—C5—H5A110.0O3—C12—C11129.70 (13)
C1—C5—H5A110.0O2—C12—C11108.82 (11)
C6—C5—H5A110.0C11—C13—H13A120.0
O2—C6—C7103.33 (9)C11—C13—H13B120.0
O2—C6—C5112.09 (9)H13A—C13—H13B120.0
C7—C6—C5113.92 (10)C4—C14—H14A109.5
O2—C6—H6A109.1C4—C14—H14B109.5
C7—C6—H6A109.1H14A—C14—H14B109.5
C5—C6—H6A109.1C4—C14—H14C109.5
C11—C7—C8119.24 (11)H14A—C14—H14C109.5
C11—C7—C6100.4 (1)H14B—C14—H14C109.5
C8—C7—C6116.17 (10)C10—C15—H15A109.5
C11—C7—H7A106.7C10—C15—H15B109.5
C8—C7—H7A106.7H15A—C15—H15B109.5
C6—C7—H7A106.7C10—C15—H15C109.5
C7—C8—C9110.86 (10)H15A—C15—H15C109.5
C7—C8—H8A109.5H15B—C15—H15C109.5
C9—C8—H8A109.5

Experimental details

Crystal data
Chemical formulaC15H16O3
Mr244.28
Crystal system, space groupOrthorhombic, P212121
Temperature (K)100
a, b, c (Å)7.5101 (3), 11.1065 (4), 15.0228 (6)
V (Å3)1253.07 (8)
Z4
Radiation typeCu Kα
µ (mm−1)0.73
Crystal size (mm)0.29 × 0.07 × 0.05
Data collection
DiffractometerBruker APEXII DUO
Absorption correctionIntegration
(SADABS; Bruker, 2008)
Tmin, Tmax0.820, 0.962
No. of measured, independent and
observed [I > 2σ(I)] reflections		10896, 2166, 2150
Rint0.064
(sin θ/λ)max (Å−1)0.594
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.027, 0.068, 1.05
No. of reflections2166
No. of parameters165
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.19, −0.14
Absolute structureFlack (1983), 879 Friedel pairs
Absolute structure parameter0.00 (17)

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

This work was partially supported by SECyTP, UNCuyo 06 J 213 grant and ANPCYT PICT-R 2005 32850 grant to LAL. We thank Florida Inter­national University, the National Science Foundation and the University of Florida for funding of the purchase of the X-ray equipment.

References

First citationBohlmann, F. & Zdero, C. (1972). Tetrahedron Lett. 13, 621–624.  CrossRef Google Scholar
 First citationBruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationGiordano, O. S., Pestchanker, J. M., Guerreiro, E., Saad, J. R., Enriz, R. D., Rodriguez, A. M., Jauregui, E. A., Maria, A. O. M. & Wendel, G. H. (1992). J. Med. Chem. 35, 2452–2458.  CrossRef PubMed CAS Web of Science Google Scholar
 First citationMartinez, M. V., Munoz-Zamora, A. & Joseph-Nathan, P. (1988). J. Nat. Prod. 51, 221–228.  Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 12| December 2011| Page o3470
https://doi.org/10.1107/S1600536811048938
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS