organic compounds
(Z)-5-(3,4,5-Trimethoxystyryl)-2,3-dihydrothieno[3,4-b][1,4]dioxine
aDepartment of Pharmacy, Yantaishan Hospital, Yantai 264000, Shandong, People's Republic of China, and bNanjing Sanhome Pharmaceutical Co. Ltd, Nanjing 210038, Jiangsu, People's Republic of China
*Correspondence e-mail: chugang_1981@163.com
In the title compound, C17H18O5S, an analogue of the potent anticancer agent combretastatin A-4, the alkene C=C bond has a cis conformation and the C—C=C—C torsion angle is 9.0 (3)°. The dihedral angle between the benzene and thiophene rings is 54.07 (4)°. The dioxene ring adopts a half-chair conformation, with the C atoms of the methylene groups displaced by −0.325 (2) and 0.341 (3) Å from the plane of the other atoms. The C atoms of the two meta-methoxy groups are close to being coplanar with their attached benzene ring [displacements = −0.025 (2) and −0.196 (2) Å], whereas the C atom of the para-methoxy group is significantly displaced [by −1.107 (2) Å]. In the crystal, C—H⋯O hydrogen bonds link the molecules into [0-11] chains, which feature two different types of R22(6) loops.
CCDC reference: 988810
Related literature
For background to combretastatin [systematic name: (Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenol], see Pettit et al. (1987, 1995); Dark et al. (1997); Thorpe et al. (2003); Tozer et al. (2005). For further synthesis details, see Mohannkrishnan et al. (1999).
Experimental
Crystal data
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Data collection: SMART (Bruker, 2008); cell SAINT (Bruker, 2008); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.
Supporting information
CCDC reference: 988810
10.1107/S1600536814004437/hb7200sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536814004437/hb7200Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536814004437/hb7200Isup3.cdx
Supporting information file. DOI: 10.1107/S1600536814004437/hb7200Isup4.cml
To the bromotriphenyl(3,4,5-trimethoxybenzyl)phosphonium salt (5.2 g,10.0 mmol) in dry THF (60 ml) at -78 °C, was added 2.5 Mn-BuLi in hexane (4.0 ml,10.0 mmol) with stirring. After 20 min., a solution of 2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carbaldehyde (1.7 g,10.0 mmol) in dry THF (20 ml) was added and resulting mixture stirred at room temperature for 2 h. Then, the mixture was poured into crushed ice, extracted with ethyl acetate (3*30 ml), dried with MgSO4, and concentrated in vacuo. The resulting solid was purified by
(petroleum ether/ ethyl acetate, V:V = 5:1) to give white product (1.38 g). Yield: 41.9%. mp. 122–123 °C. The 1H NMR, 13CNMR, MS spectra and elemental analysis are in accord with the assigned structures. Colourless blocks of the title compound were obtained by the slow evaporation of a petroleum ether/ ethyl acetate solution.Data collection: SMART (Bruker, 2008); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).Fig. 1. View of the title compound, showing 50% probability ellipsoids. | |
Fig. 2. A hydrogen-bonded chain in the title compound. |
C17H18O5S | Z = 2 |
Mr = 334.37 | F(000) = 352 |
Triclinic, P1 | Dx = 1.397 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.197 (2) Å | Cell parameters from 3471 reflections |
b = 8.4527 (15) Å | θ = 2.5–28.3° |
c = 11.835 (3) Å | µ = 0.23 mm−1 |
α = 88.774 (1)° | T = 296 K |
β = 85.484 (3)° | Block, colorless |
γ = 76.422 (2)° | 0.30 × 0.28 × 0.26 mm |
V = 794.6 (3) Å3 |
Bruker SMART CCD diffractometer | 3059 independent reflections |
Radiation source: fine-focus sealed tube | 2766 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.159 |
ω scans | θmax = 26.0°, θmin = 2.5° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −10→5 |
Tmin = 0.963, Tmax = 0.985 | k = −10→10 |
4342 measured reflections | l = −14→14 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.066 | H-atom parameters constrained |
wR(F2) = 0.179 | w = 1/[σ2(Fo2) + (0.1373P)2 + 0.0901P] where P = (Fo2 + 2Fc2)/3 |
S = 0.99 | (Δ/σ)max < 0.001 |
3059 reflections | Δρmax = 0.57 e Å−3 |
212 parameters | Δρmin = −0.69 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.75 (5) |
C17H18O5S | γ = 76.422 (2)° |
Mr = 334.37 | V = 794.6 (3) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.197 (2) Å | Mo Kα radiation |
b = 8.4527 (15) Å | µ = 0.23 mm−1 |
c = 11.835 (3) Å | T = 296 K |
α = 88.774 (1)° | 0.30 × 0.28 × 0.26 mm |
β = 85.484 (3)° |
Bruker SMART CCD diffractometer | 3059 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 2766 reflections with I > 2σ(I) |
Tmin = 0.963, Tmax = 0.985 | Rint = 0.159 |
4342 measured reflections |
R[F2 > 2σ(F2)] = 0.066 | 0 restraints |
wR(F2) = 0.179 | H-atom parameters constrained |
S = 0.99 | Δρmax = 0.57 e Å−3 |
3059 reflections | Δρmin = −0.69 e Å−3 |
212 parameters |
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 | ||
C1 | 0.7976 (2) | 0.5843 (2) | 0.05341 (13) | 0.0332 (4) | |
H1 | 0.7750 | 0.6054 | −0.0219 | 0.040* | |
C2 | 0.8766 (2) | 0.6846 (2) | 0.10955 (14) | 0.0341 (4) | |
C3 | 0.9126 (2) | 0.6527 (2) | 0.22295 (14) | 0.0346 (4) | |
C4 | 0.8656 (2) | 0.5213 (2) | 0.27815 (13) | 0.0339 (4) | |
C5 | 0.7875 (2) | 0.4201 (2) | 0.22159 (13) | 0.0339 (4) | |
H5 | 0.7591 | 0.3311 | 0.2588 | 0.041* | |
C6 | 0.75215 (19) | 0.4526 (2) | 0.10883 (13) | 0.0319 (4) | |
C7 | 0.6789 (2) | 0.3434 (2) | 0.04398 (13) | 0.0358 (4) | |
H7 | 0.7074 | 0.3418 | −0.0337 | 0.043* | |
C8 | 0.5779 (2) | 0.2464 (2) | 0.07919 (14) | 0.0362 (4) | |
H8 | 0.5606 | 0.1761 | 0.0243 | 0.043* | |
C9 | 0.4900 (2) | 0.2326 (2) | 0.19020 (14) | 0.0354 (4) | |
C10 | 0.3068 (3) | 0.2738 (3) | 0.37088 (18) | 0.0544 (6) | |
H10 | 0.2395 | 0.3115 | 0.4362 | 0.065* | |
C11 | 0.3539 (2) | 0.1146 (3) | 0.33906 (15) | 0.0439 (5) | |
C12 | 0.4559 (2) | 0.0932 (2) | 0.23456 (13) | 0.0340 (4) | |
C13 | 0.4314 (3) | −0.1752 (2) | 0.23211 (18) | 0.0548 (6) | |
H13A | 0.4955 | −0.2826 | 0.2088 | 0.066* | |
H13B | 0.3206 | −0.1585 | 0.2040 | 0.066* | |
C14 | 0.4144 (4) | −0.1663 (3) | 0.3584 (2) | 0.0671 (7) | |
H14A | 0.3653 | −0.2536 | 0.3888 | 0.081* | |
H14B | 0.5250 | −0.1809 | 0.3865 | 0.081* | |
C15 | 0.8706 (3) | 0.8662 (2) | −0.04727 (16) | 0.0465 (5) | |
H15A | 0.9172 | 0.7818 | −0.1016 | 0.070* | |
H15B | 0.9068 | 0.9631 | −0.0697 | 0.070* | |
H15C | 0.7500 | 0.8883 | −0.0437 | 0.070* | |
C16 | 0.9071 (3) | 0.9017 (3) | 0.3128 (2) | 0.0597 (6) | |
H16A | 0.8508 | 0.9574 | 0.2502 | 0.090* | |
H16B | 0.9818 | 0.9629 | 0.3387 | 0.090* | |
H16C | 0.8253 | 0.8909 | 0.3734 | 0.090* | |
C17 | 0.8570 (3) | 0.3659 (3) | 0.44741 (16) | 0.0570 (6) | |
H17A | 0.7378 | 0.3771 | 0.4470 | 0.085* | |
H17B | 0.8873 | 0.3637 | 0.5243 | 0.085* | |
H17C | 0.9152 | 0.2664 | 0.4103 | 0.085* | |
O1 | 0.92692 (17) | 0.81485 (16) | 0.06163 (10) | 0.0434 (4) | |
O2 | 1.00158 (17) | 0.74368 (16) | 0.27742 (11) | 0.0449 (4) | |
O3 | 0.90251 (18) | 0.49911 (17) | 0.38942 (10) | 0.0426 (4) | |
O4 | 0.3099 (2) | −0.0118 (2) | 0.39693 (13) | 0.0637 (5) | |
O5 | 0.51392 (17) | −0.05526 (15) | 0.18353 (10) | 0.0418 (4) | |
S1 | 0.38731 (7) | 0.39573 (6) | 0.27505 (5) | 0.0536 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0339 (8) | 0.0410 (9) | 0.0268 (7) | −0.0138 (7) | 0.0016 (6) | −0.0030 (6) |
C2 | 0.0317 (8) | 0.0386 (9) | 0.0341 (8) | −0.0145 (7) | 0.0038 (6) | −0.0020 (7) |
C3 | 0.0356 (8) | 0.0388 (9) | 0.0329 (8) | −0.0154 (7) | −0.0012 (6) | −0.0075 (7) |
C4 | 0.0352 (8) | 0.0407 (9) | 0.0268 (8) | −0.0111 (7) | 0.0003 (6) | −0.0067 (6) |
C5 | 0.0393 (9) | 0.0349 (8) | 0.0301 (8) | −0.0149 (7) | 0.0010 (6) | −0.0021 (6) |
C6 | 0.0315 (8) | 0.0367 (8) | 0.0289 (7) | −0.0119 (6) | 0.0029 (6) | −0.0069 (6) |
C7 | 0.0449 (9) | 0.0405 (9) | 0.0253 (7) | −0.0174 (7) | 0.0006 (6) | −0.0057 (6) |
C8 | 0.0430 (9) | 0.0380 (9) | 0.0314 (8) | −0.0172 (7) | 0.0007 (6) | −0.0084 (6) |
C9 | 0.0344 (8) | 0.0391 (9) | 0.0347 (8) | −0.0130 (7) | 0.0016 (6) | −0.0094 (7) |
C10 | 0.0538 (11) | 0.0611 (13) | 0.0480 (11) | −0.0191 (10) | 0.0214 (9) | −0.0226 (9) |
C11 | 0.0442 (10) | 0.0529 (11) | 0.0366 (9) | −0.0185 (8) | 0.0090 (7) | −0.0094 (8) |
C12 | 0.0341 (8) | 0.0391 (9) | 0.0300 (8) | −0.0121 (7) | 0.0030 (6) | −0.0093 (6) |
C13 | 0.0737 (14) | 0.0382 (10) | 0.0539 (12) | −0.0231 (10) | 0.0185 (10) | −0.0036 (8) |
C14 | 0.0922 (18) | 0.0546 (13) | 0.0543 (13) | −0.0253 (13) | 0.0184 (12) | 0.0081 (10) |
C15 | 0.0553 (11) | 0.0502 (11) | 0.0403 (9) | −0.0253 (9) | −0.0041 (8) | 0.0072 (8) |
C16 | 0.0674 (14) | 0.0547 (12) | 0.0625 (13) | −0.0240 (11) | −0.0031 (10) | −0.0239 (10) |
C17 | 0.0788 (15) | 0.0702 (14) | 0.0343 (9) | −0.0404 (12) | −0.0135 (9) | 0.0104 (9) |
O1 | 0.0514 (8) | 0.0488 (8) | 0.0388 (7) | −0.0296 (6) | −0.0044 (5) | 0.0062 (6) |
O2 | 0.0485 (8) | 0.0448 (8) | 0.0480 (7) | −0.0216 (6) | −0.0104 (6) | −0.0074 (6) |
O3 | 0.0574 (8) | 0.0486 (7) | 0.0284 (6) | −0.0242 (6) | −0.0078 (5) | −0.0003 (5) |
O4 | 0.0793 (11) | 0.0662 (10) | 0.0479 (8) | −0.0317 (9) | 0.0283 (7) | −0.0076 (7) |
O5 | 0.0534 (8) | 0.0344 (7) | 0.0382 (7) | −0.0164 (6) | 0.0142 (5) | −0.0073 (5) |
S1 | 0.0570 (4) | 0.0406 (4) | 0.0624 (4) | −0.0154 (3) | 0.0180 (3) | −0.0209 (2) |
C1—C2 | 1.389 (2) | C11—C12 | 1.427 (2) |
C1—C6 | 1.391 (2) | C12—O5 | 1.368 (2) |
C1—H1 | 0.9300 | C13—O5 | 1.432 (2) |
C2—O1 | 1.3611 (19) | C13—C14 | 1.492 (3) |
C2—C3 | 1.404 (2) | C13—H13A | 0.9700 |
C3—O2 | 1.3778 (18) | C13—H13B | 0.9700 |
C3—C4 | 1.392 (2) | C14—O4 | 1.444 (3) |
C4—O3 | 1.3734 (19) | C14—H14A | 0.9700 |
C4—C5 | 1.393 (2) | C14—H14B | 0.9700 |
C5—C6 | 1.396 (2) | C15—O1 | 1.428 (2) |
C5—H5 | 0.9300 | C15—H15A | 0.9600 |
C6—C7 | 1.471 (2) | C15—H15B | 0.9600 |
C7—C8 | 1.335 (2) | C15—H15C | 0.9600 |
C7—H7 | 0.9300 | C16—O2 | 1.431 (3) |
C8—C9 | 1.464 (2) | C16—H16A | 0.9600 |
C8—H8 | 0.9300 | C16—H16B | 0.9600 |
C9—C12 | 1.359 (2) | C16—H16C | 0.9600 |
C9—S1 | 1.7322 (17) | C17—O3 | 1.415 (2) |
C10—C11 | 1.363 (3) | C17—H17A | 0.9600 |
C10—S1 | 1.713 (2) | C17—H17B | 0.9600 |
C10—H10 | 0.9300 | C17—H17C | 0.9600 |
C11—O4 | 1.360 (2) | ||
C2—C1—C6 | 120.60 (14) | O5—C13—C14 | 111.46 (17) |
C2—C1—H1 | 119.7 | O5—C13—H13A | 109.3 |
C6—C1—H1 | 119.7 | C14—C13—H13A | 109.3 |
O1—C2—C1 | 124.50 (15) | O5—C13—H13B | 109.3 |
O1—C2—C3 | 115.47 (14) | C14—C13—H13B | 109.3 |
C1—C2—C3 | 120.02 (15) | H13A—C13—H13B | 108.0 |
O2—C3—C4 | 120.04 (14) | O4—C14—C13 | 111.1 (2) |
O2—C3—C2 | 120.78 (15) | O4—C14—H14A | 109.4 |
C4—C3—C2 | 119.08 (14) | C13—C14—H14A | 109.4 |
O3—C4—C3 | 115.81 (14) | O4—C14—H14B | 109.4 |
O3—C4—C5 | 123.31 (15) | C13—C14—H14B | 109.4 |
C3—C4—C5 | 120.88 (14) | H14A—C14—H14B | 108.0 |
C4—C5—C6 | 119.71 (15) | O1—C15—H15A | 109.5 |
C4—C5—H5 | 120.1 | O1—C15—H15B | 109.5 |
C6—C5—H5 | 120.1 | H15A—C15—H15B | 109.5 |
C1—C6—C5 | 119.70 (14) | O1—C15—H15C | 109.5 |
C1—C6—C7 | 118.70 (14) | H15A—C15—H15C | 109.5 |
C5—C6—C7 | 121.44 (14) | H15B—C15—H15C | 109.5 |
C8—C7—C6 | 130.10 (14) | O2—C16—H16A | 109.5 |
C8—C7—H7 | 115.0 | O2—C16—H16B | 109.5 |
C6—C7—H7 | 115.0 | H16A—C16—H16B | 109.5 |
C7—C8—C9 | 130.45 (14) | O2—C16—H16C | 109.5 |
C7—C8—H8 | 114.8 | H16A—C16—H16C | 109.5 |
C9—C8—H8 | 114.8 | H16B—C16—H16C | 109.5 |
C12—C9—C8 | 125.05 (15) | O3—C17—H17A | 109.5 |
C12—C9—S1 | 109.52 (12) | O3—C17—H17B | 109.5 |
C8—C9—S1 | 124.81 (13) | H17A—C17—H17B | 109.5 |
C11—C10—S1 | 111.34 (14) | O3—C17—H17C | 109.5 |
C11—C10—H10 | 124.3 | H17A—C17—H17C | 109.5 |
S1—C10—H10 | 124.3 | H17B—C17—H17C | 109.5 |
O4—C11—C10 | 125.54 (17) | C2—O1—C15 | 117.07 (13) |
O4—C11—C12 | 122.54 (17) | C3—O2—C16 | 114.95 (14) |
C10—C11—C12 | 111.91 (18) | C4—O3—C17 | 117.00 (13) |
C9—C12—O5 | 123.02 (14) | C11—O4—C14 | 111.51 (15) |
C9—C12—C11 | 114.32 (16) | C12—O5—C13 | 112.21 (13) |
O5—C12—C11 | 122.66 (16) | C10—S1—C9 | 92.85 (9) |
C6—C1—C2—O1 | 179.31 (15) | S1—C9—C12—O5 | 177.21 (13) |
C6—C1—C2—C3 | 0.5 (2) | C8—C9—C12—C11 | −173.91 (17) |
O1—C2—C3—O2 | −3.6 (2) | S1—C9—C12—C11 | −2.66 (19) |
C1—C2—C3—O2 | 175.28 (15) | O4—C11—C12—C9 | −178.64 (16) |
O1—C2—C3—C4 | −179.85 (14) | C10—C11—C12—C9 | 2.1 (2) |
C1—C2—C3—C4 | −1.0 (3) | O4—C11—C12—O5 | 1.5 (3) |
O2—C3—C4—O3 | 4.7 (2) | C10—C11—C12—O5 | −177.77 (17) |
C2—C3—C4—O3 | −179.03 (15) | O5—C13—C14—O4 | 63.0 (3) |
O2—C3—C4—C5 | −174.82 (15) | C1—C2—O1—C15 | 10.4 (3) |
C2—C3—C4—C5 | 1.5 (3) | C3—C2—O1—C15 | −170.77 (16) |
O3—C4—C5—C6 | 179.03 (15) | C4—C3—O2—C16 | −106.9 (2) |
C3—C4—C5—C6 | −1.5 (3) | C2—C3—O2—C16 | 76.9 (2) |
C2—C1—C6—C5 | −0.6 (2) | C3—C4—O3—C17 | −179.64 (17) |
C2—C1—C6—C7 | −176.03 (15) | C5—C4—O3—C17 | −0.2 (3) |
C4—C5—C6—C1 | 1.0 (2) | C10—C11—O4—C14 | −164.6 (2) |
C4—C5—C6—C7 | 176.38 (15) | C12—C11—O4—C14 | 16.3 (3) |
C1—C6—C7—C8 | −155.46 (19) | C13—C14—O4—C11 | −46.7 (3) |
C5—C6—C7—C8 | 29.2 (3) | C9—C12—O5—C13 | −166.87 (17) |
C6—C7—C8—C9 | 9.0 (3) | C11—C12—O5—C13 | 13.0 (2) |
C7—C8—C9—C12 | −148.21 (19) | C14—C13—O5—C12 | −43.6 (2) |
C7—C8—C9—S1 | 41.8 (3) | C11—C10—S1—C9 | −0.85 (18) |
S1—C10—C11—O4 | −179.73 (16) | C12—C9—S1—C10 | 2.00 (14) |
S1—C10—C11—C12 | −0.5 (2) | C8—C9—S1—C10 | 173.28 (16) |
C8—C9—C12—O5 | 5.9 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C15—H15B···O1i | 0.96 | 2.57 | 3.477 (3) | 157 |
C17—H17B···O3ii | 0.96 | 2.57 | 3.266 (3) | 129 |
Symmetry codes: (i) −x+2, −y+2, −z; (ii) −x+2, −y+1, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
C15—H15B···O1i | 0.96 | 2.57 | 3.477 (3) | 157 |
C17—H17B···O3ii | 0.96 | 2.57 | 3.266 (3) | 129 |
Symmetry codes: (i) −x+2, −y+2, −z; (ii) −x+2, −y+1, −z+1. |
References
Bruker (2008). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dark, G. G., Hill, S. A., Prise, V. E., Tozer, G. M., Pettit, G. R. & Chaplin, D. J. (1997). Cancer Res. 57, 1829–1834. CAS PubMed Web of Science Google Scholar
Mohannkrishnan, A. K., Hucke, A., Lyon, M. A., Lakshmikantham, M. V. & Cava, M. P. (1999). Tetrahedron, 55, 11745–11754. Google Scholar
Pettit, G. R., Singh, S. B., Niven, M. L., Hamel, E. & Schmidt, J. M. (1987). J. Nat. Prod. 50, 119–131. CSD CrossRef CAS PubMed Web of Science Google Scholar
Pettit, G. R., Temple, C. Jr, Narayanan, V. L., Varma, R., Simpson, M. J., Boyd, M. R. & Bansal, N. (1995). Anticancer Drug Res. 10, 299–309. CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Thorpe, P. E., Chaplin, D. J. & Blakey, D. C. (2003). Cancer Res. 63, 1144–1147. PubMed CAS Google Scholar
Tozer, G. M., Kanthou, C. & Baguley, B. C. (2005). Nat. Rev. Cancer, 5, 423–425. Web of Science CrossRef PubMed CAS Google Scholar
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Combretastatins are natural products with extraordinary anticancer activity, which were isolated from tree Combretum caffrum (Pettit et al.1987). Among these compounds, combretastatin A-4 ((Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenol, CA-4) possesses the most potent antitumor activity as a result of specifically targeting the vasculature of tumors. (Pettit et al. 1995; Dark et al. 1997). Its disodium phosphate prodrug has already developed and entered clinical trials (Thorpe et al.2003; Tozer et al. 2005). Therefore, CA-4 is a very attractive leading compound because of the relatively simple structure and the strong potency against a broad spectrum of human cancer cell lines. The title compound is a new CA-4 analogue, which was prepared by the Wittig reaction (Mohannkrishnan et al. 1999). The antitumor activities of the title compound against HL-60, SMMC-7721 and A549 cancer cell lines in vitro are closely to the natural CA-4. We now report the structure of the title compound (Fig. 1). The C=C bond length is 1.335 (2) Å and two aryl units are on the same sides of the double bond plane. Therefore, it exists as Z configuration. The planes of the two aryl units, benzene ring and thiophene ring, in the molecule make a dihedral angle of 54.07 (4)°. Therefore, the structure of the title compound is very similar as that of the natural combretastatin A-4 (CA-4). In the crystal structure of the title compound, the C—H···O interactions extend the molecules into a zigzag supramolecular array with dangling thiophene rings (Fig. 2).