Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801004111/cv6008sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536801004111/cv6008Isup2.hkl |
CCDC reference: 162816
Key indicators
- Single-crystal X-ray study
- T = 300 K
- Mean (C-C) = 0.003 Å
- R factor = 0.044
- wR factor = 0.128
- Data-to-parameter ratio = 15.6
checkCIF results
No syntax errors found ADDSYM reports no extra symmetry
Alert Level C:
RADNW_01 Alert C The radiation wavelength lies outside the expected range for the supplied radiation type. Expected range 1.54175-1.54180 Wavelength given = 1.54184 STRVAL_01 From the CIF: _refine_ls_abs_structure_Flack -0.300 From the CIF: _refine_ls_abs_structure_Flack_su 0.200 Alert C Flack parameter is too small General Notes
REFLT_03 From the CIF: _diffrn_reflns_theta_max 76.00 From the CIF: _reflns_number_total 2975 Count of symmetry unique reflns 1758 Completeness (_total/calc) 169.23% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 1217 Fraction of Friedel pairs measured 0.692 Are heavy atom types Z>Si present no 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.
0 Alert Level A = Potentially serious problem
0 Alert Level B = Potential problem
2 Alert Level C = Please check
The leaves of Ambrosia artemisifolia (1.0 kg) was exhaustively extracted by percolation with methanol following the method described by El-Feraly (1978). The methanol was evaporated in vacuo to afford 72 g of gummy residue, which was chromatographed on 800 g of silica gel and eluted with hexane and increasing amounts of ethyl acetate (EtOAc). Hexane–EtOAc (15:85) afforded fractions, which after repeated crystallizations from methanol yielded dihydroparthenolide as colorless needles. Dihydroparthenolide diol was synthesized by subjecting dihydroparthenolide to dihydroxylation (Norby et al., 1999) with OsO4 under catalytic conditions. To a cold solution of 4-methylmorpholine N-oxide (0.8 g, 4.4 mmol) in water (2.5 ml) and acetone (1.0 ml) was added a solution of OsO4 (1% in t-BuOH, 0.33 ml, 1.3 × 10 -5 mol). Dihydroparthenolide (1.1 g, 4.4 mmol) was added, and the reaction mixture stirred for 20 h. The reaction mixture was chromatographed on silica gel (hexane–EtOAc (1:4)) to afford colorless crystals of dihydroparthenolide diol in 85% yield.
The absolute configuration was determined by refinement of the Flack parameter. The reported configuration, which agrees with that of sesquiterpene lactones from higher plants (Fischer et al., 1979), yielded x = -0.3 (2), while the inverse configuration yielded x = 1.3 (2). The OH H-atom positions were located in a difference Fourier map and refined isotropically, with Uiso = 1.5Ueq(O). Other H atoms were placed in calculated positions with C—H bond distances 0.97 (CH), 0.97 (CH2) and 0.96 Å (CH3), Uiso = 1.2Ueq of the attached C atom (1.5 for methyl), and thereafter treated as riding. A torsional parameter was refined for each methyl group.
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: maXus (Mackay et al., 1999); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97.
C15H24O5 | Dx = 1.291 Mg m−3 |
Mr = 284.34 | Cu Kα radiation, λ = 1.54184 Å |
Orthorhombic, P212121 | Cell parameters from 25 reflections |
a = 9.2706 (13) Å | θ = 21.3–42.2° |
b = 10.4565 (8) Å | µ = 0.79 mm−1 |
c = 15.094 (3) Å | T = 300 K |
V = 1463.2 (4) Å3 | Fragment, colorless |
Z = 4 | 0.38 × 0.32 × 0.17 mm |
F(000) = 616 |
Enraf-Nonius CAD-4 diffractometer | 2731 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.018 |
Graphite monochromator | θmax = 76.0°, θmin = 5.1° |
ω–2θ scans | h = 0→11 |
Absorption correction: ψ scan (North, et al, 1968) | k = 0→13 |
Tmin = 0.808, Tmax = 0.875 | l = −18→18 |
3269 measured reflections | 3 standard reflections every 40 min |
2975 independent reflections | intensity decay: 3.3% |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.044 | w = 1/[σ2(Fo2) + (0.078P)2 + 0.2091P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.128 | (Δ/σ)max < 0.001 |
S = 1.07 | Δρmax = 0.17 e Å−3 |
2975 reflections | Δρmin = −0.15 e Å−3 |
191 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0042 (7) |
Primary atom site location: structure-invariant direct methods | Absolute structure: (Flack, 1983), 1217 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.3 (2) |
C15H24O5 | V = 1463.2 (4) Å3 |
Mr = 284.34 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 9.2706 (13) Å | µ = 0.79 mm−1 |
b = 10.4565 (8) Å | T = 300 K |
c = 15.094 (3) Å | 0.38 × 0.32 × 0.17 mm |
Enraf-Nonius CAD-4 diffractometer | 2731 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North, et al, 1968) | Rint = 0.018 |
Tmin = 0.808, Tmax = 0.875 | 3 standard reflections every 40 min |
3269 measured reflections | intensity decay: 3.3% |
2975 independent reflections |
R[F2 > 2σ(F2)] = 0.044 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.128 | Δρmax = 0.17 e Å−3 |
S = 1.07 | Δρmin = −0.15 e Å−3 |
2975 reflections | Absolute structure: (Flack, 1983), 1217 Friedel pairs |
191 parameters | Absolute structure parameter: −0.3 (2) |
0 restraints |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.25990 (19) | 0.39108 (13) | 0.31506 (12) | 0.0585 (4) | |
O2 | 0.3331 (2) | 0.20483 (16) | 0.36804 (16) | 0.0809 (6) | |
O3 | 0.19097 (14) | 0.77712 (13) | 0.35784 (9) | 0.0413 (3) | |
O4 | 0.2259 (2) | 0.54554 (17) | 0.18149 (11) | 0.0614 (5) | |
H4O | 0.303 (4) | 0.502 (4) | 0.162 (2) | 0.092* | |
O5 | 0.50052 (18) | 0.98461 (15) | 0.40080 (14) | 0.0639 (5) | |
H5O | 0.455 (4) | 1.063 (4) | 0.403 (2) | 0.096* | |
C1 | 0.2748 (2) | 0.89276 (18) | 0.35280 (14) | 0.0448 (4) | |
H1 | 0.2110 | 0.9652 | 0.3653 | 0.054* | |
C2 | 0.3248 (3) | 0.9029 (2) | 0.25695 (16) | 0.0610 (6) | |
H2A | 0.3313 | 0.9914 | 0.2382 | 0.073* | |
H2B | 0.4178 | 0.8620 | 0.2487 | 0.073* | |
C3 | 0.2076 (3) | 0.8328 (2) | 0.20715 (15) | 0.0581 (6) | |
H3A | 0.2436 | 0.7991 | 0.1515 | 0.070* | |
H3B | 0.1262 | 0.8886 | 0.1953 | 0.070* | |
C4 | 0.1657 (2) | 0.7254 (2) | 0.27012 (12) | 0.0436 (4) | |
C5 | 0.2678 (2) | 0.61033 (19) | 0.25950 (13) | 0.0432 (4) | |
H5 | 0.3665 | 0.6421 | 0.2519 | 0.052* | |
C6 | 0.2624 (2) | 0.52513 (17) | 0.34328 (14) | 0.0423 (4) | |
H6 | 0.1738 | 0.5440 | 0.3762 | 0.051* | |
C7 | 0.3911 (2) | 0.52959 (18) | 0.40717 (13) | 0.0385 (4) | |
H7 | 0.4797 | 0.5260 | 0.3719 | 0.046* | |
C8 | 0.4010 (2) | 0.64537 (18) | 0.46861 (13) | 0.0440 (4) | |
H8A | 0.4532 | 0.6207 | 0.5216 | 0.053* | |
H8B | 0.3042 | 0.6697 | 0.4864 | 0.053* | |
C9 | 0.4760 (2) | 0.76292 (19) | 0.42726 (17) | 0.0483 (5) | |
H9A | 0.5647 | 0.7777 | 0.4598 | 0.058* | |
H9B | 0.5030 | 0.7408 | 0.3671 | 0.058* | |
C10 | 0.3930 (2) | 0.88970 (19) | 0.42385 (15) | 0.0458 (5) | |
C11 | 0.3721 (2) | 0.39996 (18) | 0.45337 (14) | 0.0443 (4) | |
H11 | 0.2932 | 0.4075 | 0.4962 | 0.053* | |
C12 | 0.3218 (3) | 0.3185 (2) | 0.37812 (17) | 0.0544 (5) | |
C13 | 0.5020 (3) | 0.3444 (2) | 0.50059 (17) | 0.0568 (6) | |
H13A | 0.4764 | 0.2638 | 0.5268 | 0.085* | |
H13B | 0.5331 | 0.4023 | 0.5461 | 0.085* | |
H13C | 0.5788 | 0.3318 | 0.4588 | 0.085* | |
C14 | 0.3308 (3) | 0.9239 (2) | 0.51443 (16) | 0.0559 (5) | |
H14A | 0.4050 | 0.9172 | 0.5585 | 0.084* | |
H14B | 0.2537 | 0.8660 | 0.5286 | 0.084* | |
H14C | 0.2944 | 1.0098 | 0.5131 | 0.084* | |
C15 | 0.0085 (3) | 0.6876 (3) | 0.26291 (16) | 0.0577 (6) | |
H15A | −0.0102 | 0.6162 | 0.3012 | 0.087* | |
H15B | −0.0129 | 0.6643 | 0.2028 | 0.087* | |
H15C | −0.0511 | 0.7585 | 0.2802 | 0.087* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0715 (10) | 0.0304 (7) | 0.0735 (10) | −0.0018 (7) | −0.0253 (8) | −0.0044 (7) |
O2 | 0.0971 (14) | 0.0308 (8) | 0.1149 (17) | 0.0011 (8) | −0.0369 (13) | 0.0002 (9) |
O3 | 0.0477 (7) | 0.0342 (6) | 0.0419 (7) | −0.0009 (5) | 0.0015 (5) | 0.0019 (5) |
O4 | 0.0746 (11) | 0.0612 (10) | 0.0484 (9) | 0.0130 (8) | −0.0114 (8) | −0.0124 (8) |
O5 | 0.0526 (9) | 0.0334 (7) | 0.1056 (14) | −0.0063 (7) | 0.0076 (9) | 0.0059 (8) |
C1 | 0.0526 (10) | 0.0291 (8) | 0.0528 (11) | 0.0048 (8) | 0.0053 (9) | 0.0040 (8) |
C2 | 0.0815 (16) | 0.0440 (11) | 0.0575 (13) | −0.0012 (11) | 0.0160 (12) | 0.0131 (10) |
C3 | 0.0792 (16) | 0.0485 (12) | 0.0466 (11) | 0.0099 (11) | 0.0054 (11) | 0.0134 (9) |
C4 | 0.0507 (10) | 0.0430 (10) | 0.0372 (9) | 0.0076 (9) | −0.0007 (8) | 0.0035 (8) |
C5 | 0.0489 (10) | 0.0395 (9) | 0.0413 (9) | 0.0042 (8) | −0.0027 (8) | −0.0017 (8) |
C6 | 0.0462 (10) | 0.0287 (8) | 0.0519 (10) | −0.0002 (7) | −0.0058 (8) | −0.0013 (8) |
C7 | 0.0426 (9) | 0.0296 (8) | 0.0433 (9) | 0.0011 (7) | −0.0013 (7) | 0.0036 (7) |
C8 | 0.0502 (10) | 0.0351 (9) | 0.0468 (10) | 0.0001 (8) | −0.0055 (8) | 0.0002 (8) |
C9 | 0.0406 (9) | 0.0334 (9) | 0.0710 (13) | 0.0011 (8) | −0.0032 (9) | −0.0012 (9) |
C10 | 0.0434 (10) | 0.0289 (9) | 0.0650 (12) | −0.0009 (7) | 0.0018 (9) | 0.0013 (9) |
C11 | 0.0480 (10) | 0.0323 (9) | 0.0527 (11) | 0.0002 (8) | 0.0001 (8) | 0.0083 (8) |
C12 | 0.0567 (12) | 0.0332 (10) | 0.0732 (14) | −0.0024 (8) | −0.0126 (11) | 0.0050 (9) |
C13 | 0.0640 (13) | 0.0438 (11) | 0.0625 (13) | 0.0024 (11) | −0.0102 (11) | 0.0133 (10) |
C14 | 0.0604 (13) | 0.0442 (11) | 0.0630 (13) | 0.0041 (10) | −0.0052 (10) | −0.0096 (10) |
C15 | 0.0507 (11) | 0.0700 (15) | 0.0525 (12) | 0.0081 (11) | −0.0086 (10) | 0.0035 (11) |
O1—C12 | 1.346 (3) | C6—H6 | 0.9800 |
O1—C6 | 1.465 (2) | C7—C8 | 1.528 (3) |
O2—C12 | 1.203 (3) | C7—C11 | 1.534 (2) |
O3—C1 | 1.439 (2) | C7—H7 | 0.9800 |
O3—C4 | 1.450 (2) | C8—C9 | 1.544 (3) |
O4—C5 | 1.413 (2) | C8—H8A | 0.9700 |
O4—H4O | 0.90 (4) | C8—H8B | 0.9700 |
O5—C10 | 1.449 (2) | C9—C10 | 1.534 (3) |
O5—H5O | 0.92 (4) | C9—H9A | 0.9700 |
C1—C2 | 1.523 (3) | C9—H9B | 0.9700 |
C1—C10 | 1.534 (3) | C10—C14 | 1.526 (3) |
C1—H1 | 0.9800 | C11—C12 | 1.495 (3) |
C2—C3 | 1.511 (4) | C11—C13 | 1.515 (3) |
C2—H2A | 0.9700 | C11—H11 | 0.9800 |
C2—H2B | 0.9700 | C13—H13A | 0.9600 |
C3—C4 | 1.522 (3) | C13—H13B | 0.9600 |
C3—H3A | 0.9700 | C13—H13C | 0.9600 |
C3—H3B | 0.9700 | C14—H14A | 0.9600 |
C4—C15 | 1.514 (3) | C14—H14B | 0.9600 |
C4—C5 | 1.539 (3) | C14—H14C | 0.9600 |
C5—C6 | 1.548 (3) | C15—H15A | 0.9600 |
C5—H5 | 0.9800 | C15—H15B | 0.9600 |
C6—C7 | 1.535 (3) | C15—H15C | 0.9600 |
C12—O1—C6 | 109.11 (16) | C7—C8—C9 | 114.36 (18) |
C1—O3—C4 | 110.65 (14) | C7—C8—H8A | 108.7 |
C5—O4—H4O | 107 (2) | C9—C8—H8A | 108.7 |
C10—O5—H5O | 107 (2) | C7—C8—H8B | 108.7 |
O3—C1—C2 | 105.84 (17) | C9—C8—H8B | 108.7 |
O3—C1—C10 | 109.36 (15) | H8A—C8—H8B | 107.6 |
C2—C1—C10 | 116.6 (2) | C10—C9—C8 | 118.40 (17) |
O3—C1—H1 | 108.2 | C10—C9—H9A | 107.7 |
C2—C1—H1 | 108.2 | C8—C9—H9A | 107.7 |
C10—C1—H1 | 108.2 | C10—C9—H9B | 107.7 |
C3—C2—C1 | 102.71 (19) | C8—C9—H9B | 107.7 |
C3—C2—H2A | 111.2 | H9A—C9—H9B | 107.1 |
C1—C2—H2A | 111.2 | O5—C10—C14 | 108.36 (18) |
C3—C2—H2B | 111.2 | O5—C10—C1 | 108.02 (18) |
C1—C2—H2B | 111.2 | C14—C10—C1 | 110.57 (18) |
H2A—C2—H2B | 109.1 | O5—C10—C9 | 104.78 (16) |
C2—C3—C4 | 103.34 (18) | C14—C10—C9 | 111.21 (19) |
C2—C3—H3A | 111.1 | C1—C10—C9 | 113.57 (17) |
C4—C3—H3A | 111.1 | C12—C11—C13 | 112.78 (18) |
C2—C3—H3B | 111.1 | C12—C11—C7 | 101.18 (16) |
C4—C3—H3B | 111.1 | C13—C11—C7 | 117.50 (17) |
H3A—C3—H3B | 109.1 | C12—C11—H11 | 108.3 |
O3—C4—C15 | 108.58 (17) | C13—C11—H11 | 108.3 |
O3—C4—C3 | 104.68 (17) | C7—C11—H11 | 108.3 |
C15—C4—C3 | 113.16 (19) | O2—C12—O1 | 120.3 (2) |
O3—C4—C5 | 106.71 (15) | O2—C12—C11 | 129.2 (2) |
C15—C4—C5 | 112.40 (19) | O1—C12—C11 | 110.44 (17) |
C3—C4—C5 | 110.79 (17) | C11—C13—H13A | 109.5 |
O4—C5—C4 | 107.00 (17) | C11—C13—H13B | 109.5 |
O4—C5—C6 | 113.33 (16) | H13A—C13—H13B | 109.5 |
C4—C5—C6 | 110.16 (16) | C11—C13—H13C | 109.5 |
O4—C5—H5 | 108.8 | H13A—C13—H13C | 109.5 |
C4—C5—H5 | 108.8 | H13B—C13—H13C | 109.5 |
C6—C5—H5 | 108.8 | C10—C14—H14A | 109.5 |
O1—C6—C7 | 102.93 (15) | C10—C14—H14B | 109.5 |
O1—C6—C5 | 108.27 (16) | H14A—C14—H14B | 109.5 |
C7—C6—C5 | 118.07 (16) | C10—C14—H14C | 109.5 |
O1—C6—H6 | 109.1 | H14A—C14—H14C | 109.5 |
C7—C6—H6 | 109.1 | H14B—C14—H14C | 109.5 |
C5—C6—H6 | 109.1 | C4—C15—H15A | 109.5 |
C8—C7—C11 | 115.53 (16) | C4—C15—H15B | 109.5 |
C8—C7—C6 | 116.88 (16) | H15A—C15—H15B | 109.5 |
C11—C7—C6 | 99.78 (15) | C4—C15—H15C | 109.5 |
C8—C7—H7 | 108.0 | H15A—C15—H15C | 109.5 |
C11—C7—H7 | 108.0 | H15B—C15—H15C | 109.5 |
C6—C7—H7 | 108.0 | ||
C4—O3—C1—C2 | −9.1 (2) | O1—C6—C7—C11 | −38.4 (2) |
C4—O3—C1—C10 | −135.49 (16) | C5—C6—C7—C11 | −157.55 (16) |
O3—C1—C2—C3 | 27.9 (2) | C11—C7—C8—C9 | 157.72 (17) |
C10—C1—C2—C3 | 149.75 (18) | C6—C7—C8—C9 | −85.3 (2) |
C1—C2—C3—C4 | −35.5 (2) | C7—C8—C9—C10 | 123.2 (2) |
C1—O3—C4—C15 | −134.60 (18) | O3—C1—C10—O5 | 162.79 (15) |
C1—O3—C4—C3 | −13.5 (2) | C2—C1—C10—O5 | 42.8 (2) |
C1—O3—C4—C5 | 104.03 (17) | O3—C1—C10—C14 | −78.8 (2) |
C2—C3—C4—O3 | 30.6 (2) | C2—C1—C10—C14 | 161.21 (19) |
C2—C3—C4—C15 | 148.6 (2) | O3—C1—C10—C9 | 47.0 (2) |
C2—C3—C4—C5 | −84.1 (2) | C2—C1—C10—C9 | −73.0 (2) |
O3—C4—C5—O4 | 169.53 (16) | C8—C9—C10—O5 | 167.66 (19) |
C15—C4—C5—O4 | 50.6 (2) | C8—C9—C10—C14 | 50.8 (3) |
C3—C4—C5—O4 | −77.1 (2) | C8—C9—C10—C1 | −74.7 (3) |
O3—C4—C5—C6 | 45.9 (2) | C8—C7—C11—C12 | 163.36 (17) |
C15—C4—C5—C6 | −73.0 (2) | C6—C7—C11—C12 | 37.16 (19) |
C3—C4—C5—C6 | 159.33 (18) | C8—C7—C11—C13 | −73.4 (2) |
C12—O1—C6—C7 | 25.4 (2) | C6—C7—C11—C13 | 160.37 (19) |
C12—O1—C6—C5 | 151.16 (19) | C6—O1—C12—O2 | −179.0 (3) |
O4—C5—C6—O1 | 18.0 (2) | C6—O1—C12—C11 | −0.7 (3) |
C4—C5—C6—O1 | 137.79 (18) | C13—C11—C12—O2 | 27.5 (4) |
O4—C5—C6—C7 | 134.27 (19) | C7—C11—C12—O2 | 153.9 (3) |
C4—C5—C6—C7 | −105.9 (2) | C13—C11—C12—O1 | −150.6 (2) |
O1—C6—C7—C8 | −163.68 (17) | C7—C11—C12—O1 | −24.2 (2) |
C5—C6—C7—C8 | 77.2 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4O···O5i | 0.90 (4) | 2.06 (4) | 2.895 (3) | 154 (3) |
O5—H5O···O2ii | 0.92 (4) | 1.94 (4) | 2.821 (2) | 160 (3) |
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) x, y+1, z. |
Experimental details
Crystal data | |
Chemical formula | C15H24O5 |
Mr | 284.34 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 300 |
a, b, c (Å) | 9.2706 (13), 10.4565 (8), 15.094 (3) |
V (Å3) | 1463.2 (4) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.79 |
Crystal size (mm) | 0.38 × 0.32 × 0.17 |
Data collection | |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | ψ scan (North, et al, 1968) |
Tmin, Tmax | 0.808, 0.875 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3269, 2975, 2731 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.629 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.128, 1.07 |
No. of reflections | 2975 |
No. of parameters | 191 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.17, −0.15 |
Absolute structure | (Flack, 1983), 1217 Friedel pairs |
Absolute structure parameter | −0.3 (2) |
Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1994), CAD-4 EXPRESS, maXus (Mackay et al., 1999), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), ORTEPIII (Burnett & Johnson, 1996), SHELXL97.
C4—O3—C1—C2 | −9.1 (2) | C5—C6—C7—C8 | 77.2 (2) |
O3—C1—C2—C3 | 27.9 (2) | O1—C6—C7—C11 | −38.4 (2) |
C10—C1—C2—C3 | 149.75 (18) | C6—C7—C8—C9 | −85.3 (2) |
C1—C2—C3—C4 | −35.5 (2) | C7—C8—C9—C10 | 123.2 (2) |
C1—O3—C4—C3 | −13.5 (2) | C2—C1—C10—C9 | −73.0 (2) |
C2—C3—C4—O3 | 30.6 (2) | C8—C9—C10—C1 | −74.7 (3) |
C2—C3—C4—C5 | −84.1 (2) | C6—C7—C11—C12 | 37.16 (19) |
C3—C4—C5—C6 | 159.33 (18) | C6—O1—C12—C11 | −0.7 (3) |
C12—O1—C6—C7 | 25.4 (2) | C7—C11—C12—O1 | −24.2 (2) |
C4—C5—C6—C7 | −105.9 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4O···O5i | 0.90 (4) | 2.06 (4) | 2.895 (3) | 154 (3) |
O5—H5O···O2ii | 0.92 (4) | 1.94 (4) | 2.821 (2) | 160 (3) |
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) x, y+1, z. |
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The α,β-unsaturated lactones have aroused much interest in medicine because of their remarkable biological properties, mainly as cytotoxic, antitumor, and bactericidal agents (El-Feraly & Chan, 1978). Among these compounds, sesquiterpenes (α-methylene-γ-lactones) have been intensively studied using both medicinal and chemical approaches (Picman, 1986). Recently, it has been shown that sesquiterpene lactones stimulate germination of Striga seeds at concentrations lower than 10-5 M (Rugutt, 1996). Striga (witchweed) are parasitic weeds that cause severe damage to graminaceous and leguminous crops in tropical and semitropical areas of the eastern hemisphere (Nour et al., 1983).
We have recently begun a program aimed at synthesis and separation (Shamsi & Warner, 1997) of antimycobacterial agents. Specifically, a long-range goal of our efforts in this area is to rationally design novel classes of drugs against the multidrug-resistant Mycobacterium tuberculosis and M. avium. It is important to recognize that dihydroparthenolide contains the 4,5-epoxide as a reactive receptor site. Although this epoxide function is not directly accessible due to steric hindrance of the associated medium ring structure, it provides increased reactivity as well as regio- and stereospecificity of subsequent intramolecular cyclizations. We envision that the reaction of dihydroparthenolide with OsO4 lead to the formation of a 1,10-diol (both OH α-oriented). This diol undergoes a Markovnikov-type transannular cyclization to afford dihydroparthenolide diol, (I). In the 400 MHz 1H NMR spectrum of (I), a doublet at δ 3.66 was attributed to H-5 which coupled with H-6. The signal of H-6 (δ 4.17) appeared as a well defined one-proton of doublet with large coupling constants (J5,6 = 10.4 Hz; J6,7 = 7.2 Hz). This indicated a trans-axial relationship between H-5, H-6 and H-7, i.e. H-5 α, H-6 β, and H-7 α-oriented. The stereochemistry of methylene proton resonances (which overlapped at δ 1.4–2.3) could not be determined from the NMR data. In order to unambiguously assign the stereochemistry of dihydroparthenolide diol, the crystal structure was determined.
The structure (Fig. 1) is identical to that of the naturally occurring achillifolin (Ulubelen, et al., 1990), except that the title compound has a β-methyl group and an α-OH at C10 rather than an exocyclic CH2 group. The tetrahydrofuran ring has the half-chair conformation with O3 on the twist axis, and asymmetry parameter (Duax & Norton, 1975) ΔC2 = 3.5°. The α-methyl-γ-lactone is trans-fused at C6—C7, and has its methyl group α-oriented, with C11 having the S configuration. The conformation of the lactone ring is an envelope, with C7 at the flap position, and asymmetry parameter ΔCs = 1.0°. O—H···O hydrogen bonding (Table 2) form chains in the [010] direction. The crystal structure of dihydroparthenolide has been reported (Rugutt & Rugutt, 1997).
Dihydroparthenolide diol and dihydroparthenolide were tested against Mycobacterium tuberculosis and M. avium. Stock solutions (10.24 mg ml-1) were dissolved in DMSO and filter sterilized. The bioassay was performed by a broth dilution method as previously reported (Franzblau, 1989). The MICs of both compounds against M. tuberculosis and M. avium was 128 µg ml-1. The minimum inhibitory concentration (MIC) is the lowest concentration of the compound needed to inhibit 99% of the organisms.