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In the title compound, C15H18O4, the methyl groups adopt a syn conformation, with the hydr­oxy group in an anti conformation relative to both methyl groups. The mol­ecules are linked by inter­molecular O—H...O hydrogen bonds involving a carbonyl and a hydroxyl group.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805030795/ac6170sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536805030795/ac6170Isup2.hkl
Contains datablock I

CCDC reference: 287424

Key indicators

  • Single-crystal X-ray study
  • T = 289 K
  • Mean [sigma](C-C) = 0.004 Å
  • R factor = 0.039
  • wR factor = 0.084
  • Data-to-parameter ratio = 10.1

checkCIF/PLATON results

No syntax errors found



Alert level C STRVA01_ALERT_2_C Chirality of atom sites is inverted? From the CIF: _refine_ls_abs_structure_Flack 3.700 From the CIF: _refine_ls_abs_structure_Flack_su 1.800 PLAT032_ALERT_4_C Std. Uncertainty in Flack Parameter too High ... 1.80 PLAT033_ALERT_2_C Flack Parameter Value Deviates from Zero ....... 3.70 PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size ....... 0.62 mm PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given ....... ?
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 27.75 From the CIF: _reflns_number_total 1810 Count of symmetry unique reflns 1810 Completeness (_total/calc) 100.00% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 0 Fraction of Friedel pairs measured 0.000 Are heavy atom types Z>Si present no
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 5 ALERT level C = Check and explain 1 ALERT level G = General alerts; check 0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 2 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 3 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

Sesquiterpenoids have received much attention on account of their structurally novel carbon skeletons and bioactivity (Fraga et al., 1995, 1996, 1997, 1998, 1999a,b, Fraga et al., 2000; Peng et al., 1997; Shi et al., 1999; Wu et al., 2004a,b; Yang et al., 2002). An eremophilane-type sesquiterpenoid, 10α-hydroxy-1-oxoeremophila-7(11),8(9)-dien-12, 8-olide, (I), was isolated from the medicinal plant Ligularia virgaurea spp. oligocephala Good, which is used for treatment of stomach ache and nausea (Wu 1985). The structure of (I), obtained by spectroscopic methods, was previously reported (Wu et al., 2004a). The hydroxyl group on C-10 was established as being α-oriented by the larger coupling constant between H-3β (axial bond) and H-4α (axial bond), J3β,4α = 13.6 Hz, in accordance with 4β,5β-Me (Massiot et al., 1990). The crystal structure analysis of (I) was undertaken to establish the structure and relative stereochemistry unambiguously.

Cytotoxicity against selected cancer cells human promyelocytic leukemia (HL-60), human ovarian (HO-8910) and human lung epithehial (A-549) of compound (I) were measured in vitro using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method (Niu et al., 2002; Toume et al., 2004). Compared to etoposide (VP-16), compound (I) exhibited no significant inhibitory effects with IC50 values over 100 µM.

An ORTEP-3 drawing (Farrugia, 1997) of the molecule is shown in Fig. 1. The bond lengths and angles have normal values (Allen et al., 1987), with the following average values (Å): Csp3—Csp3 = 1.535 (3), Csp3—Csp2 = 1.508 (3), Csp2—Csp2 = 1.393 (3), CO = 1.205 (3) and C—O = 1.411 (3). Ring A is in a twisted-chair conformation, with average torsion angles of 52.6 (3)°. Ring C is almost planar with a mean torsion angles of 0.98 (2)°. The torsion angle C6—C7—C8—C9 is 0.0 (4)° and C7—C8—C9—C10 is 2.6 (4)°; it is shown that atoms C6–C10 was almost coplanar with ring C, and ring B adopts an envelope conformation. The dihedral angle between the plane passing through atoms C6–C10 and atoms C6–C5–C10 of the molecule is 55.4 (2)°.

The X-ray analysis of (I) shows that the hydroxyl group with α-orientation is located on C10 and the methyl-14 and the methyl-15 groups with β-orientation are located on C5 and C4, as reported previously based on spectroscopic methods (Wu et al., 2004a or Wu et al., 2004b?). An interesting feature of the packing of the structure is that two methyl groups, C4—C15 and C5—C14, exhibit a syn conformation, and the hydroxyl group, C10—O3, exhibits an anti conformation with the two methyl groups, even though MM2 calculations indicate that this conformer should be around 3.9 kcal mol−1 less stable than C4—C15 and C10—O3 exhibiting a syn conformation and C5—C14 exhibiting an anti conformation. It is suggested that the compound crystallizes as that conformer in order to facilitate the formation of classical hydrogen bond. The crystal packing is stabilized by intermolecular O—H···O hydrogen bonds involving the hydroxyl group and the C1-carbonyl group (Table 1). The hydrogen bonds link the molecules into chains along the b axis (Fig. 2).

Experimental top

The dried and powdered roots of Ligularia virgaurea spp. oligocephala Good (4.0 kg) were extracted three times with 95% EtOH at room temperature. After evaporation under reduced pressure, the residue was then suspended in H2O, extracted with petroleum ether (333–363 K), EtOAc and n-BuOH, respectively. The EtOAc extract (75 g) was separated by repeated silica gel (200–300 me s h) column chromatography and recrystallization, giving compound (I) (yield: 7 mg; m.p. 450–451 K; optical rotation: [α]D25 −87.0°). Crystals suitable for X-ray diffraction measurements were obtained by slow evaporation of a solution of (I) in CHCl3/CH3OH at room temperature. The MTT method was reported in the literature (Niu et al., 2002; Toume et al., 2004).

Refinement top

All H atoms were placed in calculated positions (O—H = 0.82 Å and C—H = 0.93–0.98 Å) and allowed to ride on the carrier atom, with Uiso(H) values constrained to be 1.5Ueq of the carrier atom for methyl H atoms and 1.2Ueq for the remaining H atoms. Friedel reflections were merged before the final refinement because of the absence of significant anomalous scattering effects.

Computing details top

Data collection: XSCANS (Siemens 1994); cell refinement: XSCANS; data reduction: SHELXTL (Bruker 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. ORTEP-3 (Farrugia, 1997) plot of the title compound. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. The molecular packing of (I), viewed along the a axis. Dashed lines represent O—H···O hydrogen bonds. Only the H atoms involved in hydrogen bonding are shown..
10α-Hydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide top
Crystal data top
C15H18O4Dx = 1.328 Mg m3
Mr = 262.29Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 38 reflections
a = 6.885 (2) Åθ = 4.8–14.6°
b = 6.969 (2) ŵ = 0.10 mm1
c = 27.348 (9) ÅT = 289 K
V = 1312.2 (7) Å3Block, colourless
Z = 40.62 × 0.24 × 0.10 mm
F(000) = 560
Data collection top
Siemens P4
diffractometer
Rint = 0.017
Radiation source: normal-focus sealed tubeθmax = 27.8°, θmin = 1.5°
Graphite monochromatorh = 09
ω scansk = 09
1943 measured reflectionsl = 135
1810 independent reflections3 standard reflections every 97 reflections
1255 reflections with I > 2σ(I) intensity decay: 2.8%
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.039 w = 1/[σ2(Fo2) + (0.0416P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.084(Δ/σ)max < 0.001
S = 0.91Δρmax = 0.17 e Å3
1810 reflectionsΔρmin = 0.15 e Å3
180 parametersExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.013 (2)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 3.7 (18)
Crystal data top
C15H18O4V = 1312.2 (7) Å3
Mr = 262.29Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 6.885 (2) ŵ = 0.10 mm1
b = 6.969 (2) ÅT = 289 K
c = 27.348 (9) Å0.62 × 0.24 × 0.10 mm
Data collection top
Siemens P4
diffractometer
Rint = 0.017
1943 measured reflections3 standard reflections every 97 reflections
1810 independent reflections intensity decay: 2.8%
1255 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.039H-atom parameters constrained
wR(F2) = 0.084Δρmax = 0.17 e Å3
S = 0.91Δρmin = 0.15 e Å3
1810 reflectionsAbsolute structure: Flack (1983)
180 parametersAbsolute structure parameter: 3.7 (18)
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. 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 > σ(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
O10.1059 (2)0.1052 (2)0.09328 (6)0.0439 (5)
O20.0539 (3)0.6271 (3)0.21861 (6)0.0474 (5)
O30.2935 (3)0.3119 (2)0.20765 (6)0.0408 (5)
H3O0.22180.24870.22540.049*
O40.1141 (3)0.0623 (3)0.02258 (7)0.0640 (6)
C10.1148 (4)0.6010 (4)0.20783 (8)0.0351 (6)
C20.2772 (4)0.7254 (4)0.22633 (9)0.0471 (7)
H2A0.34420.65820.25240.057*
H2B0.22240.84180.24000.057*
C30.4239 (4)0.7795 (4)0.18704 (9)0.0427 (7)
H3A0.36670.87560.16580.051*
H3B0.53670.83650.20250.051*
C40.4891 (4)0.6097 (4)0.15619 (8)0.0333 (6)
H40.55510.51960.17810.040*
C50.3136 (3)0.5030 (3)0.13384 (7)0.0279 (5)
C60.3817 (4)0.3259 (3)0.10428 (8)0.0344 (6)
H6A0.45580.36790.07610.041*
H6B0.46570.24720.12450.041*
C70.2121 (4)0.2102 (3)0.08773 (8)0.0324 (6)
C80.0352 (4)0.2163 (3)0.11600 (8)0.0334 (6)
C90.0080 (4)0.3175 (3)0.15637 (8)0.0346 (6)
H90.11160.31900.17220.042*
C100.1781 (4)0.4303 (3)0.17578 (7)0.0292 (5)
C110.1817 (4)0.0979 (3)0.04869 (8)0.0372 (6)
C120.0202 (4)0.0318 (4)0.05057 (9)0.0435 (7)
C130.3154 (5)0.0427 (4)0.00774 (9)0.0550 (8)
H13A0.27500.10560.02180.081 (11)*
H13B0.31120.09380.00310.090 (11)*
H13C0.44560.08100.01570.102 (14)*
C140.1983 (4)0.6363 (3)0.09990 (8)0.0347 (6)
H14A0.28420.69100.07600.042*
H14B0.13990.73700.11880.042*
H14C0.09860.56420.08360.042*
C150.6382 (4)0.6757 (4)0.11841 (9)0.0487 (7)
H15A0.57620.75770.09490.058*
H15B0.69170.56590.10200.058*
H15C0.74030.74490.13450.058*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0476 (10)0.0384 (9)0.0457 (9)0.0132 (9)0.0022 (10)0.0026 (9)
O20.0449 (11)0.0531 (12)0.0443 (10)0.0044 (10)0.0100 (9)0.0120 (10)
O30.0455 (10)0.0421 (10)0.0349 (9)0.0041 (10)0.0004 (9)0.0134 (8)
O40.0878 (16)0.0522 (12)0.0520 (11)0.0229 (13)0.0206 (12)0.0099 (10)
C10.0418 (15)0.0404 (14)0.0231 (11)0.0033 (14)0.0040 (11)0.0017 (11)
C20.0537 (17)0.0498 (16)0.0378 (13)0.0001 (16)0.0008 (14)0.0167 (13)
C30.0452 (16)0.0407 (14)0.0422 (13)0.0097 (14)0.0010 (13)0.0106 (13)
C40.0332 (13)0.0366 (13)0.0301 (11)0.0037 (13)0.0013 (11)0.0001 (12)
C50.0300 (12)0.0300 (11)0.0236 (10)0.0001 (12)0.0026 (10)0.0001 (9)
C60.0362 (13)0.0343 (13)0.0328 (13)0.0017 (12)0.0061 (11)0.0026 (11)
C70.0408 (14)0.0247 (11)0.0317 (12)0.0020 (12)0.0021 (12)0.0018 (11)
C80.0367 (14)0.0291 (12)0.0343 (11)0.0052 (12)0.0023 (11)0.0005 (11)
C90.0364 (14)0.0345 (13)0.0330 (11)0.0051 (13)0.0055 (11)0.0025 (11)
C100.0324 (13)0.0315 (12)0.0237 (10)0.0030 (12)0.0014 (10)0.0020 (10)
C110.0556 (16)0.0249 (11)0.0312 (12)0.0013 (14)0.0008 (12)0.0036 (11)
C120.0641 (19)0.0279 (12)0.0384 (14)0.0029 (14)0.0069 (15)0.0014 (12)
C130.085 (2)0.0421 (17)0.0375 (15)0.0024 (19)0.0085 (16)0.0067 (13)
C140.0395 (13)0.0327 (12)0.0319 (12)0.0026 (12)0.0027 (12)0.0041 (11)
C150.0447 (17)0.0575 (17)0.0439 (14)0.0158 (15)0.0030 (13)0.0001 (14)
Geometric parameters (Å, º) top
O1—C81.389 (3)C6—C71.489 (3)
O1—C121.405 (3)C6—H6A0.9700
O2—C11.212 (3)C6—H6B0.9700
O3—C101.440 (3)C7—C111.341 (3)
O3—H3O0.8200C7—C81.443 (3)
O4—C121.197 (3)C8—C91.324 (3)
C1—C21.503 (3)C9—C101.507 (3)
C1—C101.540 (3)C9—H90.9300
C2—C31.522 (3)C11—C121.466 (4)
C2—H2A0.9700C11—C131.500 (3)
C2—H2B0.9700C13—H13A0.9600
C3—C41.521 (3)C13—H13B0.9600
C3—H3A0.9700C13—H13C0.9600
C3—H3B0.9700C14—H14A0.9600
C4—C151.527 (3)C14—H14B0.9600
C4—C51.546 (3)C14—H14C0.9600
C4—H40.9800C15—H15A0.9600
C5—C141.535 (3)C15—H15B0.9600
C5—C61.548 (3)C15—H15C0.9600
C5—C101.563 (3)
C8—O1—C12106.31 (19)C8—C7—C6118.88 (19)
C10—O3—H3O109.5C9—C8—O1124.8 (2)
O2—C1—C2123.0 (2)C9—C8—C7125.6 (2)
O2—C1—C10121.7 (2)O1—C8—C7109.55 (19)
C2—C1—C10115.3 (2)C8—C9—C10117.5 (2)
C1—C2—C3113.5 (2)C8—C9—H9121.2
C1—C2—H2A108.9C10—C9—H9121.2
C3—C2—H2A108.9O3—C10—C9110.06 (18)
C1—C2—H2B108.9O3—C10—C1104.74 (17)
C3—C2—H2B108.9C9—C10—C1112.5 (2)
H2A—C2—H2B107.7O3—C10—C5107.50 (17)
C4—C3—C2113.2 (2)C9—C10—C5111.97 (17)
C4—C3—H3A108.9C1—C10—C5109.66 (18)
C2—C3—H3A108.9C7—C11—C12107.7 (2)
C4—C3—H3B108.9C7—C11—C13130.4 (3)
C2—C3—H3B108.9C12—C11—C13121.9 (2)
H3A—C3—H3B107.7O4—C12—O1120.3 (3)
C3—C4—C15109.8 (2)O4—C12—C11131.4 (3)
C3—C4—C5111.28 (19)O1—C12—C11108.3 (2)
C15—C4—C5113.76 (19)C11—C13—H13A109.5
C3—C4—H4107.2C11—C13—H13B109.5
C15—C4—H4107.2H13A—C13—H13B109.5
C5—C4—H4107.2C11—C13—H13C109.5
C14—C5—C4110.64 (19)H13A—C13—H13C109.5
C14—C5—C6108.87 (17)H13B—C13—H13C109.5
C4—C5—C6110.68 (19)C5—C14—H14A109.5
C14—C5—C10109.35 (19)C5—C14—H14B109.5
C4—C5—C10109.42 (17)H14A—C14—H14B109.5
C6—C5—C10107.83 (18)C5—C14—H14C109.5
C7—C6—C5110.65 (19)H14A—C14—H14C109.5
C7—C6—H6A109.5H14B—C14—H14C109.5
C5—C6—H6A109.5C4—C15—H15A109.5
C7—C6—H6B109.5C4—C15—H15B109.5
C5—C6—H6B109.5H15A—C15—H15B109.5
H6A—C6—H6B108.1C4—C15—H15C109.5
C11—C7—C8108.2 (2)H15A—C15—H15C109.5
C11—C7—C6132.9 (2)H15B—C15—H15C109.5
O2—C1—C2—C3136.0 (3)C8—C9—C10—C532.1 (3)
C10—C1—C2—C346.7 (3)O2—C1—C10—O3113.9 (3)
C1—C2—C3—C447.1 (3)C2—C1—C10—O363.4 (2)
C2—C3—C4—C15179.0 (2)O2—C1—C10—C95.6 (3)
C2—C3—C4—C554.1 (3)C2—C1—C10—C9177.1 (2)
C3—C4—C5—C1461.5 (2)O2—C1—C10—C5131.0 (2)
C15—C4—C5—C1463.2 (3)C2—C1—C10—C551.7 (3)
C3—C4—C5—C6177.74 (18)C14—C5—C10—O3177.92 (17)
C15—C4—C5—C657.6 (3)C4—C5—C10—O356.6 (2)
C3—C4—C5—C1059.1 (2)C6—C5—C10—O363.9 (2)
C15—C4—C5—C10176.2 (2)C14—C5—C10—C961.1 (2)
C14—C5—C6—C764.9 (2)C4—C5—C10—C9177.59 (18)
C4—C5—C6—C7173.29 (18)C6—C5—C10—C957.2 (2)
C10—C5—C6—C753.6 (2)C14—C5—C10—C164.6 (2)
C5—C6—C7—C11150.1 (2)C4—C5—C10—C156.7 (2)
C5—C6—C7—C827.1 (3)C6—C5—C10—C1177.17 (19)
C12—O1—C8—C9176.7 (2)C8—C7—C11—C121.3 (2)
C12—O1—C8—C70.9 (2)C6—C7—C11—C12176.2 (2)
C11—C7—C8—C9177.8 (2)C8—C7—C11—C13180.0 (3)
C6—C7—C8—C90.0 (4)C6—C7—C11—C132.5 (4)
C11—C7—C8—O10.3 (3)C8—O1—C12—O4176.3 (2)
C6—C7—C8—O1177.61 (19)C8—O1—C12—C111.6 (2)
O1—C8—C9—C10179.8 (2)C7—C11—C12—O4175.8 (3)
C7—C8—C9—C102.6 (4)C13—C11—C12—O43.1 (4)
C8—C9—C10—O387.4 (2)C7—C11—C12—O11.8 (2)
C8—C9—C10—C1156.2 (2)C13—C11—C12—O1179.3 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3O···O2i0.822.102.906 (2)169
Symmetry code: (i) x, y1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC15H18O4
Mr262.29
Crystal system, space groupOrthorhombic, P212121
Temperature (K)289
a, b, c (Å)6.885 (2), 6.969 (2), 27.348 (9)
V3)1312.2 (7)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.62 × 0.24 × 0.10
Data collection
DiffractometerSiemens P4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
1943, 1810, 1255
Rint0.017
(sin θ/λ)max1)0.655
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.084, 0.91
No. of reflections1810
No. of parameters180
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.17, 0.15
Absolute structureFlack (1983)
Absolute structure parameter3.7 (18)

Computer programs: XSCANS (Siemens 1994), XSCANS, SHELXTL (Bruker 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL.

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3O···O2i0.822.102.906 (2)169
Symmetry code: (i) x, y1/2, z+1/2.
 

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