organic compounds
(E)-13-(2-Bromophenyl)micheliolide
aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA, and bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA
*Correspondence e-mail: pacrooks@uams.edu
The title compound, C21H23BrO3 [systematic name: (3E,3aS,6Z,9R,9aS,9bS)-3-(2-bromobenzylidene)-9-hydroxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one] was prepared by the reaction of 1-bromo-2-iodobenzene with micheliolide [systematic name: (3aS,R,9aS,9bS,Z)-9-hydroxy-6,9-dimethyl-3-methylene-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one] under Heck reaction conditions. The title compound exhibits intramolecular O—H⋯O hydrogen bonding between the hydroxy group and the lactone ring O atom, forming a ring of graph-set motif S(6). The 2-bromophenyl group is trans to the lactone ring, indicating that this is the E isomer (geometry of the exocyclic C=C bond). The dihedral angle between the benzene ring of the 2-bromophenyl moiety and the mean plane of the lactone ring is 51.68 (7)°.
CCDC reference: 984233
Related literature
For the biological activity of micheliolide Michael addition compounds, see: Rodriguez et al. (1976); Sethi et al. (1984); Neelakantan et al. (2009); Zhang et al. (2012). For details of the Heck chemistry, see: Han et al. (2009). For the of micheliolide, see: Acosta et al. (1991). For the of a similar compound, see: Penthala et al. (2013).
Experimental
Crystal data
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Refinement
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Data collection: COLLECT (Nonius, 1998); cell SCALEPACK (Otwinowski & Minor, 2006); data reduction: DENZO-SMN (Otwinowski & Minor, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: XP in SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008b).
Supporting information
CCDC reference: 984233
10.1107/S1600536814002177/sj5372sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814002177/sj5372Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814002177/sj5372Isup3.cml
A mixture of micheliolide (prepared from parthenolide, Zhang et al., 2012) (50 mg, 0.20 mmol), triethylamine (60 mg, 0.61 mmol), and 1-bromo-2-iodobenzene (63 mg, 0.22 mmol) in dimethylformamide (1 ml) was treated with palladium(II) acetate (0.5 mg, 0.002 mmol) and then stirred at 353 K for 24 h. The reaction mixture was cooled to room temperature, water (8 ml) was added, and the mixture was extracted with ethyl acetate (10 ml x 3). The separated organics were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified using silica flash δ 7.70–7.70 (d, J=2.8 Hz, 1H), 7.62–7.64 (d, J=8.0 Hz, 1H), 7.22–7.35 (m, 3H, Ar—H and =CH), 3.89–3.94 (t, J=10 Hz, 20.4 Hz, 1H), 3.01–3.06 (t, J=8.8 Hz, 19.6 Hz, 1H), 2.73–2.76 (d, J=11.2 Hz, 1H), 2.71 (s, 1H), 2.35–2.41 (m, 1H), 2.01–2.21 (m, 1H), 1.76–1.89 (m, 3H), 1.61 (s, 3H), 1.32 (s, 3H), 1.00–1.04 (m, 1H) p.p.m.. 13C NMR (100 MHz, CDCl3): δ 22.57, 23.69, 24.91, 29.86, 35.36, 38.23, 48.93, 58.99, 80.79, 124.14, 126.93, 129.86, 130.47, 130.55, 131.03, 131.50, 132.86, 134.54, 136.70, 170.68 p.p.m..
(7:3, hexanes/EtOAc) to afford the title compound, which was recrystallized from hexanes as colorless needles suitable for X-ray analysis (65 mg, 80% yield; M·P: 421–423 K); 1H NMR (400 MHz, CDCl3):H atoms were found in difference Fourier maps. Carbon-bound H atoms were subsequently placed at idealized positions with constrained distances of 0.98 Å (RCH3), 0.99 Å (R2CH2), 1.00 Å (R3CH) and 0.95 Å (Csp2H). The hydroxy hydrogen coordinates were refined. Uiso(H) values were set to either 1.2Ueq or 1.5Ueq (RCH3, OH) of the attached atom.
Data collection: COLLECT (Nonius, 1998); cell
SCALEPACK (Otwinowski & Minor, 2006); data reduction: DENZO-SMN (Otwinowski & Minor, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: XP in SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008b).Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level. |
C21H23BrO3 | Dx = 1.478 Mg m−3 |
Mr = 403.30 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 127083 reflections |
a = 7.1617 (1) Å | θ = 1.0–27.5° |
b = 13.1615 (2) Å | µ = 2.29 mm−1 |
c = 19.2306 (3) Å | T = 90 K |
V = 1812.65 (5) Å3 | Block, cut from needle, colourless |
Z = 4 | 0.20 × 0.20 × 0.15 mm |
F(000) = 832 |
Nonius KappaCCD diffractometer | 4148 independent reflections |
Radiation source: fine-focus sealed-tube | 3871 reflections with I > 2σ(I) |
Detector resolution: 9.1 pixels mm-1 | Rint = 0.047 |
φ and ω scans at fixed χ = 55° | θmax = 27.5°, θmin = 1.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a) | h = −9→9 |
Tmin = 0.550, Tmax = 0.714 | k = −17→17 |
48139 measured reflections | l = −24→24 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.025 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.064 | w = 1/[σ2(Fo2) + (0.0352P)2 + 0.4253P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
4148 reflections | Δρmax = 0.41 e Å−3 |
231 parameters | Δρmin = −0.34 e Å−3 |
0 restraints | Absolute structure: Flack parameter determined using 1569 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.032 (3) |
C21H23BrO3 | V = 1812.65 (5) Å3 |
Mr = 403.30 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 7.1617 (1) Å | µ = 2.29 mm−1 |
b = 13.1615 (2) Å | T = 90 K |
c = 19.2306 (3) Å | 0.20 × 0.20 × 0.15 mm |
Nonius KappaCCD diffractometer | 4148 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a) | 3871 reflections with I > 2σ(I) |
Tmin = 0.550, Tmax = 0.714 | Rint = 0.047 |
48139 measured reflections |
R[F2 > 2σ(F2)] = 0.025 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.064 | Δρmax = 0.41 e Å−3 |
S = 1.04 | Δρmin = −0.34 e Å−3 |
4148 reflections | Absolute structure: Flack parameter determined using 1569 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
231 parameters | Absolute structure parameter: 0.032 (3) |
0 restraints |
Experimental. The crystal was mounted with polyisobutene oil on the tip of a fine glass fibre, fastened in a copper mounting pin with electrical solder. It was placed directly into the cold stream of a liquid nitrogen based cryostat. Diffraction data were collected with the crystal at 90 K, which is standard practice in this laboratory for the majority of flash-cooled crystals. |
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. |
x | y | z | Uiso*/Ueq | ||
Br1 | 0.79983 (4) | −0.11654 (2) | 0.35920 (2) | 0.03215 (9) | |
O1 | 0.7715 (3) | 0.26157 (14) | 0.45446 (10) | 0.0248 (4) | |
O2 | 0.5251 (3) | 0.34175 (14) | 0.40803 (9) | 0.0215 (4) | |
O3 | 0.3499 (3) | 0.53339 (15) | 0.43985 (11) | 0.0285 (5) | |
H3 | 0.434 (6) | 0.498 (3) | 0.444 (2) | 0.043* | |
C1 | 0.0338 (3) | 0.3743 (2) | 0.33548 (13) | 0.0202 (5) | |
C2 | −0.0575 (4) | 0.4794 (2) | 0.33076 (16) | 0.0252 (6) | |
H2A | −0.0553 | 0.5046 | 0.2823 | 0.030* | |
H2B | −0.1887 | 0.4765 | 0.3468 | 0.030* | |
C3 | 0.0577 (4) | 0.5486 (2) | 0.37792 (14) | 0.0243 (6) | |
H3A | 0.0633 | 0.6184 | 0.3589 | 0.029* | |
H3B | 0.0037 | 0.5512 | 0.4253 | 0.029* | |
C4 | 0.2513 (4) | 0.50008 (19) | 0.37900 (13) | 0.0208 (5) | |
C5 | 0.2022 (3) | 0.38520 (18) | 0.38337 (12) | 0.0185 (4) | |
H5 | 0.1602 | 0.3704 | 0.4319 | 0.022* | |
C6 | 0.3602 (3) | 0.31433 (18) | 0.36651 (14) | 0.0192 (5) | |
H6 | 0.3917 | 0.3211 | 0.3161 | 0.023* | |
C7 | 0.3212 (4) | 0.20208 (18) | 0.38266 (13) | 0.0198 (5) | |
H7 | 0.2314 | 0.1984 | 0.4224 | 0.024* | |
C8 | 0.2325 (4) | 0.1511 (2) | 0.31966 (14) | 0.0237 (6) | |
H8A | 0.2408 | 0.0764 | 0.3251 | 0.028* | |
H8B | 0.3031 | 0.1702 | 0.2774 | 0.028* | |
C9 | 0.0275 (4) | 0.1814 (2) | 0.31045 (16) | 0.0259 (6) | |
H9A | −0.0413 | 0.1538 | 0.3509 | 0.031* | |
H9B | −0.0193 | 0.1449 | 0.2690 | 0.031* | |
C10 | −0.0321 (4) | 0.2927 (2) | 0.30252 (14) | 0.0212 (5) | |
C11 | 0.5102 (4) | 0.1654 (2) | 0.40740 (13) | 0.0201 (5) | |
C12 | 0.6223 (4) | 0.2566 (2) | 0.42595 (13) | 0.0204 (5) | |
C13 | 0.5791 (4) | 0.07309 (19) | 0.42009 (13) | 0.0210 (5) | |
H13 | 0.7092 | 0.0697 | 0.4295 | 0.025* | |
C14 | −0.2025 (4) | 0.3016 (2) | 0.25629 (14) | 0.0257 (5) | |
H14A | −0.2471 | 0.3720 | 0.2565 | 0.039* | |
H14B | −0.3011 | 0.2567 | 0.2738 | 0.039* | |
H14C | −0.1695 | 0.2817 | 0.2087 | 0.039* | |
C15 | 0.3630 (4) | 0.5270 (2) | 0.31404 (15) | 0.0255 (6) | |
H15A | 0.3776 | 0.6010 | 0.3111 | 0.038* | |
H15B | 0.2969 | 0.5024 | 0.2727 | 0.038* | |
H15C | 0.4864 | 0.4951 | 0.3165 | 0.038* | |
C16 | 0.4774 (4) | −0.0247 (2) | 0.42131 (13) | 0.0204 (5) | |
C17 | 0.5616 (4) | −0.1163 (2) | 0.40254 (13) | 0.0220 (5) | |
C18 | 0.4756 (4) | −0.2095 (2) | 0.41364 (14) | 0.0252 (6) | |
H18 | 0.5356 | −0.2707 | 0.3999 | 0.030* | |
C19 | 0.3015 (5) | −0.21243 (19) | 0.44500 (14) | 0.0261 (6) | |
H19 | 0.2434 | −0.2759 | 0.4542 | 0.031* | |
C20 | 0.2116 (4) | −0.1224 (2) | 0.46308 (13) | 0.0251 (5) | |
H20 | 0.0909 | −0.1244 | 0.4835 | 0.030* | |
C21 | 0.2988 (4) | −0.02945 (19) | 0.45117 (13) | 0.0228 (5) | |
H21 | 0.2364 | 0.0317 | 0.4634 | 0.027* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.03169 (14) | 0.02821 (14) | 0.03656 (15) | 0.00934 (12) | 0.00802 (12) | 0.00322 (13) |
O1 | 0.0264 (10) | 0.0225 (9) | 0.0254 (9) | −0.0003 (8) | −0.0026 (8) | 0.0020 (8) |
O2 | 0.0249 (9) | 0.0140 (8) | 0.0256 (9) | −0.0014 (7) | −0.0045 (7) | 0.0001 (7) |
O3 | 0.0383 (12) | 0.0152 (9) | 0.0319 (11) | 0.0016 (8) | −0.0109 (9) | −0.0040 (8) |
C1 | 0.0231 (11) | 0.0163 (12) | 0.0212 (11) | −0.0009 (10) | 0.0027 (9) | 0.0025 (10) |
C2 | 0.0257 (13) | 0.0145 (12) | 0.0355 (15) | 0.0004 (10) | −0.0034 (11) | 0.0028 (11) |
C3 | 0.0301 (13) | 0.0148 (12) | 0.0281 (14) | 0.0020 (10) | 0.0017 (11) | 0.0004 (10) |
C4 | 0.0289 (12) | 0.0112 (11) | 0.0224 (13) | −0.0009 (9) | −0.0046 (10) | −0.0001 (9) |
C5 | 0.0231 (11) | 0.0120 (10) | 0.0204 (10) | −0.0016 (12) | 0.0008 (9) | 0.0005 (9) |
C6 | 0.0242 (11) | 0.0148 (11) | 0.0185 (12) | −0.0012 (9) | −0.0028 (10) | −0.0006 (10) |
C7 | 0.0258 (12) | 0.0119 (11) | 0.0218 (12) | −0.0010 (10) | 0.0007 (10) | −0.0009 (9) |
C8 | 0.0304 (14) | 0.0162 (12) | 0.0246 (13) | 0.0016 (10) | −0.0023 (11) | −0.0038 (10) |
C9 | 0.0290 (13) | 0.0172 (13) | 0.0316 (14) | 0.0001 (11) | −0.0044 (11) | −0.0055 (11) |
C10 | 0.0229 (12) | 0.0187 (13) | 0.0221 (13) | 0.0003 (10) | 0.0010 (10) | 0.0000 (10) |
C11 | 0.0261 (13) | 0.0175 (13) | 0.0168 (12) | 0.0002 (10) | 0.0008 (10) | 0.0004 (10) |
C12 | 0.0254 (13) | 0.0176 (12) | 0.0182 (12) | −0.0011 (10) | 0.0006 (10) | 0.0013 (10) |
C13 | 0.0255 (13) | 0.0184 (12) | 0.0191 (12) | −0.0010 (10) | 0.0022 (10) | 0.0006 (10) |
C14 | 0.0236 (12) | 0.0222 (13) | 0.0312 (14) | −0.0014 (12) | −0.0005 (12) | −0.0016 (11) |
C15 | 0.0262 (13) | 0.0179 (13) | 0.0323 (15) | −0.0013 (10) | −0.0030 (11) | 0.0043 (11) |
C16 | 0.0277 (13) | 0.0157 (12) | 0.0179 (12) | 0.0002 (10) | −0.0028 (11) | 0.0009 (10) |
C17 | 0.0243 (12) | 0.0205 (12) | 0.0211 (12) | 0.0033 (12) | −0.0017 (9) | 0.0009 (11) |
C18 | 0.0360 (15) | 0.0148 (13) | 0.0247 (14) | 0.0045 (11) | −0.0032 (12) | −0.0021 (11) |
C19 | 0.0361 (14) | 0.0163 (12) | 0.0259 (13) | −0.0040 (13) | −0.0051 (14) | 0.0014 (10) |
C20 | 0.0275 (12) | 0.0214 (12) | 0.0264 (12) | −0.0042 (13) | −0.0001 (11) | 0.0025 (11) |
C21 | 0.0279 (12) | 0.0155 (12) | 0.0251 (12) | 0.0024 (12) | −0.0004 (13) | 0.0019 (10) |
Br1—C17 | 1.899 (3) | C8—H8B | 0.9900 |
O1—C12 | 1.203 (3) | C9—C10 | 1.533 (4) |
O2—C12 | 1.364 (3) | C9—H9A | 0.9900 |
O2—C6 | 1.470 (3) | C9—H9B | 0.9900 |
O3—C4 | 1.435 (3) | C10—C14 | 1.514 (4) |
O3—H3 | 0.77 (4) | C11—C13 | 1.335 (4) |
C1—C10 | 1.333 (4) | C11—C12 | 1.487 (4) |
C1—C5 | 1.525 (3) | C13—C16 | 1.479 (4) |
C1—C2 | 1.532 (4) | C13—H13 | 0.9500 |
C2—C3 | 1.527 (4) | C14—H14A | 0.9800 |
C2—H2A | 0.9900 | C14—H14B | 0.9800 |
C2—H2B | 0.9900 | C14—H14C | 0.9800 |
C3—C4 | 1.527 (4) | C15—H15A | 0.9800 |
C3—H3A | 0.9900 | C15—H15B | 0.9800 |
C3—H3B | 0.9900 | C15—H15C | 0.9800 |
C4—C15 | 1.525 (4) | C16—C17 | 1.396 (4) |
C4—C5 | 1.555 (3) | C16—C21 | 1.403 (4) |
C5—C6 | 1.502 (3) | C17—C18 | 1.389 (4) |
C5—H5 | 1.0000 | C18—C19 | 1.386 (4) |
C6—C7 | 1.535 (3) | C18—H18 | 0.9500 |
C6—H6 | 1.0000 | C19—C20 | 1.393 (4) |
C7—C11 | 1.514 (4) | C19—H19 | 0.9500 |
C7—C8 | 1.524 (4) | C20—C21 | 1.392 (4) |
C7—H7 | 1.0000 | C20—H20 | 0.9500 |
C8—C9 | 1.532 (4) | C21—H21 | 0.9500 |
C8—H8A | 0.9900 | ||
C12—O2—C6 | 110.22 (19) | C8—C9—H9A | 106.9 |
C4—O3—H3 | 106 (3) | C10—C9—H9A | 106.9 |
C10—C1—C5 | 130.0 (2) | C8—C9—H9B | 106.9 |
C10—C1—C2 | 123.2 (2) | C10—C9—H9B | 106.9 |
C5—C1—C2 | 106.8 (2) | H9A—C9—H9B | 106.7 |
C3—C2—C1 | 105.8 (2) | C1—C10—C14 | 120.2 (2) |
C3—C2—H2A | 110.6 | C1—C10—C9 | 128.6 (2) |
C1—C2—H2A | 110.6 | C14—C10—C9 | 110.8 (2) |
C3—C2—H2B | 110.6 | C13—C11—C12 | 119.4 (2) |
C1—C2—H2B | 110.6 | C13—C11—C7 | 132.7 (2) |
H2A—C2—H2B | 108.7 | C12—C11—C7 | 107.5 (2) |
C4—C3—C2 | 104.4 (2) | O1—C12—O2 | 121.6 (2) |
C4—C3—H3A | 110.9 | O1—C12—C11 | 129.3 (2) |
C2—C3—H3A | 110.9 | O2—C12—C11 | 109.1 (2) |
C4—C3—H3B | 110.9 | C11—C13—C16 | 127.8 (2) |
C2—C3—H3B | 110.9 | C11—C13—H13 | 116.1 |
H3A—C3—H3B | 108.9 | C16—C13—H13 | 116.1 |
O3—C4—C15 | 109.8 (2) | C10—C14—H14A | 109.5 |
O3—C4—C3 | 109.3 (2) | C10—C14—H14B | 109.5 |
C15—C4—C3 | 111.6 (2) | H14A—C14—H14B | 109.5 |
O3—C4—C5 | 111.4 (2) | C10—C14—H14C | 109.5 |
C15—C4—C5 | 112.9 (2) | H14A—C14—H14C | 109.5 |
C3—C4—C5 | 101.7 (2) | H14B—C14—H14C | 109.5 |
C6—C5—C1 | 114.0 (2) | C4—C15—H15A | 109.5 |
C6—C5—C4 | 115.0 (2) | C4—C15—H15B | 109.5 |
C1—C5—C4 | 103.7 (2) | H15A—C15—H15B | 109.5 |
C6—C5—H5 | 107.9 | C4—C15—H15C | 109.5 |
C1—C5—H5 | 107.9 | H15A—C15—H15C | 109.5 |
C4—C5—H5 | 107.9 | H15B—C15—H15C | 109.5 |
O2—C6—C5 | 109.59 (19) | C17—C16—C21 | 117.4 (2) |
O2—C6—C7 | 105.82 (19) | C17—C16—C13 | 122.3 (2) |
C5—C6—C7 | 114.6 (2) | C21—C16—C13 | 119.7 (2) |
O2—C6—H6 | 108.9 | C18—C17—C16 | 122.1 (2) |
C5—C6—H6 | 108.9 | C18—C17—Br1 | 117.7 (2) |
C7—C6—H6 | 108.9 | C16—C17—Br1 | 120.2 (2) |
C11—C7—C8 | 118.8 (2) | C19—C18—C17 | 119.3 (3) |
C11—C7—C6 | 102.0 (2) | C19—C18—H18 | 120.3 |
C8—C7—C6 | 109.8 (2) | C17—C18—H18 | 120.3 |
C11—C7—H7 | 108.6 | C18—C19—C20 | 120.1 (2) |
C8—C7—H7 | 108.6 | C18—C19—H19 | 120.0 |
C6—C7—H7 | 108.6 | C20—C19—H19 | 120.0 |
C7—C8—C9 | 112.1 (2) | C21—C20—C19 | 119.9 (2) |
C7—C8—H8A | 109.2 | C21—C20—H20 | 120.0 |
C9—C8—H8A | 109.2 | C19—C20—H20 | 120.0 |
C7—C8—H8B | 109.2 | C20—C21—C16 | 121.0 (3) |
C9—C8—H8B | 109.2 | C20—C21—H21 | 119.5 |
H8A—C8—H8B | 107.9 | C16—C21—H21 | 119.5 |
C8—C9—C10 | 121.8 (2) | ||
C10—C1—C2—C3 | 178.0 (2) | C2—C1—C10—C14 | 1.5 (4) |
C5—C1—C2—C3 | −1.5 (3) | C5—C1—C10—C9 | 8.9 (5) |
C1—C2—C3—C4 | 26.5 (3) | C2—C1—C10—C9 | −170.6 (3) |
C2—C3—C4—O3 | −158.4 (2) | C8—C9—C10—C1 | −39.4 (4) |
C2—C3—C4—C15 | 80.0 (3) | C8—C9—C10—C14 | 147.9 (3) |
C2—C3—C4—C5 | −40.6 (3) | C8—C7—C11—C13 | −48.2 (4) |
C10—C1—C5—C6 | 31.2 (4) | C6—C7—C11—C13 | −169.0 (3) |
C2—C1—C5—C6 | −149.3 (2) | C8—C7—C11—C12 | 138.5 (2) |
C10—C1—C5—C4 | 157.0 (3) | C6—C7—C11—C12 | 17.7 (3) |
C2—C1—C5—C4 | −23.5 (3) | C6—O2—C12—O1 | 173.0 (2) |
O3—C4—C5—C6 | −79.2 (3) | C6—O2—C12—C11 | −9.5 (3) |
C15—C4—C5—C6 | 44.9 (3) | C13—C11—C12—O1 | −3.0 (4) |
C3—C4—C5—C6 | 164.5 (2) | C7—C11—C12—O1 | 171.3 (3) |
O3—C4—C5—C1 | 155.6 (2) | C13—C11—C12—O2 | 179.7 (2) |
C15—C4—C5—C1 | −80.3 (2) | C7—C11—C12—O2 | −6.0 (3) |
C3—C4—C5—C1 | 39.3 (2) | C12—C11—C13—C16 | 164.5 (2) |
C12—O2—C6—C5 | 145.0 (2) | C7—C11—C13—C16 | −8.2 (5) |
C12—O2—C6—C7 | 21.0 (3) | C11—C13—C16—C17 | 148.9 (3) |
C1—C5—C6—O2 | 171.08 (19) | C11—C13—C16—C21 | −40.2 (4) |
C4—C5—C6—O2 | 51.4 (3) | C21—C16—C17—C18 | −1.1 (4) |
C1—C5—C6—C7 | −70.1 (3) | C13—C16—C17—C18 | 170.0 (3) |
C4—C5—C6—C7 | 170.2 (2) | C21—C16—C17—Br1 | 178.06 (18) |
O2—C6—C7—C11 | −22.9 (2) | C13—C16—C17—Br1 | −10.8 (3) |
C5—C6—C7—C11 | −143.8 (2) | C16—C17—C18—C19 | −0.7 (4) |
O2—C6—C7—C8 | −149.8 (2) | Br1—C17—C18—C19 | −179.9 (2) |
C5—C6—C7—C8 | 89.3 (3) | C17—C18—C19—C20 | 2.0 (4) |
C11—C7—C8—C9 | 168.4 (2) | C18—C19—C20—C21 | −1.6 (4) |
C6—C7—C8—C9 | −74.9 (3) | C19—C20—C21—C16 | −0.3 (4) |
C7—C8—C9—C10 | 57.4 (4) | C17—C16—C21—C20 | 1.6 (4) |
C5—C1—C10—C14 | −179.1 (2) | C13—C16—C21—C20 | −169.8 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O2 | 0.77 (4) | 2.26 (4) | 2.883 (3) | 139 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O2 | 0.77 (4) | 2.26 (4) | 2.883 (3) | 139 (4) |
Acknowledgements
This work was supported by the NIH/NCI [grant No. CA158275].
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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.
Micheliolide (MCL) belongs to the class of guaianolide sesquiterpene lactones, which are being developed for the treatment of cancer (Sethi et al., 1984 and Zhang et al., 2012). The exocyclic double bond in such sesquiterpenes is believed to be responsible for their biological properties because of its exceptional chemical reactivity with nucleophilic groups (Rodriguez et al., 1976). The MCL crystal structure was described by Acosta et al. (1991). Recently, micheliolide Michael addition analogs were reported as potent anti-leukemic agents (Zhang et al., 2012). In a recent communication we reported the crystal structure of (E)-13-(4-aminophenyl)parthenolide, a Heck reaction derivative of parthenolide (Penthala et al., 2013). Now, in continuation of our research on sesquiterpene lactones as anti-leukemic agents (Neelakantan et al., 2009), we are focusing on the synthesis of the title E-olefinic analogue of micheliolide, which was obtained from the reaction of micheliolide with 1-bromo-2-iodobenzene utilizing Heck chemistry (Han et al., 2009). In order to obtain detailed information on the structural conformation of the title compound and to establish the geometry of the exocyclic double bond, a single-crystal X-ray structure determination has been carried out.
Recrystallization of the title compound from hexanes gave colorless needles that were suitable for X-ray analysis. The title molecule, Fig. 1, contains a central seven-membered carbocyclic ring fused to a 5-membered carbocylic ring and a trans lactone ring. The two five-membered rings are in half-chair conformations, as reported in the literature for the parent compound, micheliolide (Acosta et al., 1991). The X-ray studies revealed that the title compound exhibits intramolecular O—H···O hydrogen bonding to form a ring of graph-set motif S(6). The 2-bromophenyl group is oriented trans to the lactone ring to form the E isomer (geometry of the exocyclic C═C bond). The H atom of the hydroxy group in the molecule forms an intramolecular hydrogen bond with the lactone ring oxygen atom. The dihedral angle between the benzene ring of the 2-bromophenyl group and the mean plane of the lactone ring is 51.68 (7)°.