Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270102003669/bk1630sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270102003669/bk1630VIsup2.hkl |
CCDC reference: 188616
To a well stirred solution of 2-(3-tert-butyldimethylsiloxy-4-methoxyphenyl)-6-methoxyindole (0.511 g, 1.33 mmol) in o-dichlorobenzene (10 ml) was added 3,4,5-trimethoxybenzoylchloride (0.464 g, 2.01 mmol, 1.51 equivalents). The reaction mixture was refluxed for 12 h, after which the excess of o-dichlorobenzene was removed in vacuo and the resulting dark solid was subjected to flash chromatography (silica gel, 25% EtOAc in hexanes) to afford the title compound as a yellow powder. Recrystallization from hexanes–EtOAc afforded indole (VI) as prismatic pale-yellow crystals (0.355 g, 0.614 mmol, 46% yield, m.p. 438–440 K). 1H NMR (300 MHz, CDCl3): δ 0.035 (3H, s), 0.93 (9H, s), 3.69 (6H, s), 3.75 (3H, s), 3.79 (3H, s), 3.87 (3H, s), 6.71 (1H, d, J = 8.8 Hz), 6.77 (1H, d, J = 2.3 Hz) 6.87–6.94 (3H, m), 6.99 (2H, s), 7.95 (1H, d, J = 9.9 Hz), 8.39 (1H, s, broad).
The indolic H atom was located in a difference Fourier synthesis and was allowed to refine with a fixed isotropic displacement parameter of Uiso(H) = 1.2Uew(N). All other H atoms were constrained to idealized geometries and were assigned isotropic displacement parameters Uiso(H) = 1.2Ueq(C), or Uiso(H) = 1.5Ueq(C) for methyl H atoms. The final electron-density difference synthesis indicated a randomly fluctuating background with no significant residual peaks.
Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms, 1993); program(s) used to solve structure: SHELXTL/PC (Sheldrick, 1995); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC; software used to prepare material for publication: SHELXL97.
Fig. 1. Displacement ellipsoid plot (40% probability) of (VI) with the atom labels. All H atoms, except for the indole NH atom, have been omitted for clarity. |
C32H39NO7Si | Dx = 1.249 Mg m−3 |
Mr = 577.73 | Melting point = 165–167 K |
Orthorhombic, Pbca | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ac 2ab | Cell parameters from 25 reflections |
a = 14.596 (1) Å | θ = 10.1–16.2° |
b = 14.753 (1) Å | µ = 0.12 mm−1 |
c = 28.531 (4) Å | T = 173 K |
V = 6143.8 (10) Å3 | Prism, pale yellow |
Z = 8 | 0.55 × 0.49 × 0.49 mm |
F(000) = 2464 |
Enraf-Nonius CAD-4 diffractometer | 3841 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.017 |
Graphite monochromator | θmax = 25.0°, θmin = 2.0° |
ω–2θ scans | h = 0→17 |
Absorption correction: ψ scan (SHELXTL/PC; Sheldrick, 1995) | k = 0→17 |
Tmin = 0.926, Tmax = 0.945 | l = −2→33 |
5570 measured reflections | 3 standard reflections every 120 min |
5335 independent reflections | intensity decay: 10.1% |
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)] = 0.048 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.127 | w = 1/[σ2(Fo2) + (0.0242P)2 + 12.4107P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
5335 reflections | Δρmax = 0.37 e Å−3 |
374 parameters | Δρmin = −0.41 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.00155 (13) |
C32H39NO7Si | V = 6143.8 (10) Å3 |
Mr = 577.73 | Z = 8 |
Orthorhombic, Pbca | Mo Kα radiation |
a = 14.596 (1) Å | µ = 0.12 mm−1 |
b = 14.753 (1) Å | T = 173 K |
c = 28.531 (4) Å | 0.55 × 0.49 × 0.49 mm |
Enraf-Nonius CAD-4 diffractometer | 3841 reflections with I > 2σ(I) |
Absorption correction: ψ scan (SHELXTL/PC; Sheldrick, 1995) | Rint = 0.017 |
Tmin = 0.926, Tmax = 0.945 | 3 standard reflections every 120 min |
5570 measured reflections | intensity decay: 10.1% |
5335 independent reflections |
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.127 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0242P)2 + 12.4107P] where P = (Fo2 + 2Fc2)/3 |
5335 reflections | Δρmax = 0.37 e Å−3 |
374 parameters | Δρmin = −0.41 e Å−3 |
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 | ||
N | −0.26520 (16) | 0.69893 (16) | 0.08777 (9) | 0.0216 (6) | |
H | −0.265 (2) | 0.754 (2) | 0.0939 (11) | 0.026* | |
C1 | −0.19566 (19) | 0.64124 (18) | 0.09920 (10) | 0.0206 (6) | |
C2 | −0.22425 (19) | 0.55248 (18) | 0.09141 (10) | 0.0198 (6) | |
C3 | −0.31885 (19) | 0.55737 (18) | 0.07709 (10) | 0.0205 (6) | |
C4 | −0.3875 (2) | 0.49437 (19) | 0.06624 (10) | 0.0245 (7) | |
H4 | −0.3741 | 0.4314 | 0.0664 | 0.029* | |
C5 | −0.4740 (2) | 0.5237 (2) | 0.05541 (11) | 0.0273 (7) | |
H5 | −0.5208 | 0.4805 | 0.0493 | 0.033* | |
C6 | −0.49468 (19) | 0.6165 (2) | 0.05321 (11) | 0.0260 (7) | |
C7 | −0.42859 (19) | 0.68083 (19) | 0.06209 (11) | 0.0243 (7) | |
H7 | −0.4419 | 0.7437 | 0.0600 | 0.029* | |
C8 | −0.34182 (19) | 0.65030 (18) | 0.07422 (10) | 0.0203 (6) | |
C9 | −0.1747 (2) | 0.46659 (18) | 0.09576 (10) | 0.0215 (6) | |
C10 | −0.0720 (2) | 0.46222 (18) | 0.09404 (10) | 0.0217 (6) | |
C11 | −0.02167 (19) | 0.52018 (18) | 0.06576 (11) | 0.0226 (7) | |
H11 | −0.0509 | 0.5693 | 0.0503 | 0.027* | |
C12 | 0.0719 (2) | 0.50587 (19) | 0.06023 (10) | 0.0226 (6) | |
C13 | 0.11448 (19) | 0.43387 (19) | 0.08323 (11) | 0.0244 (7) | |
C14 | 0.0642 (2) | 0.37725 (19) | 0.11293 (10) | 0.0243 (7) | |
C15 | −0.0296 (2) | 0.39121 (19) | 0.11797 (11) | 0.0244 (7) | |
H15 | −0.0646 | 0.3525 | 0.1376 | 0.029* | |
C16 | −0.11208 (19) | 0.68028 (18) | 0.12034 (11) | 0.0213 (6) | |
C17 | −0.0698 (2) | 0.75465 (19) | 0.09989 (11) | 0.0240 (7) | |
H17 | −0.0929 | 0.7784 | 0.0713 | 0.029* | |
C18 | 0.0061 (2) | 0.79479 (19) | 0.12074 (11) | 0.0266 (7) | |
H18 | 0.0346 | 0.8454 | 0.1063 | 0.032* | |
C19 | 0.04000 (19) | 0.76124 (19) | 0.16246 (11) | 0.0257 (7) | |
C20 | −0.00169 (19) | 0.68562 (19) | 0.18311 (11) | 0.0227 (6) | |
C21 | −0.07642 (19) | 0.64579 (19) | 0.16210 (11) | 0.0226 (6) | |
H21 | −0.1041 | 0.5942 | 0.1762 | 0.027* | |
C22 | −0.6570 (2) | 0.5927 (3) | 0.05076 (16) | 0.0493 (10) | |
H22A | −0.7133 | 0.6240 | 0.0412 | 0.074* | |
H22B | −0.6600 | 0.5787 | 0.0843 | 0.074* | |
H22C | −0.6507 | 0.5364 | 0.0329 | 0.074* | |
C23 | 0.0932 (2) | 0.6410 (2) | 0.01586 (12) | 0.0299 (7) | |
H23A | 0.1394 | 0.6707 | −0.0037 | 0.045* | |
H23B | 0.0784 | 0.6800 | 0.0426 | 0.045* | |
H23C | 0.0377 | 0.6303 | −0.0027 | 0.045* | |
C24 | 0.2281 (2) | 0.3636 (3) | 0.03850 (13) | 0.0472 (10) | |
H24A | 0.2947 | 0.3569 | 0.0357 | 0.071* | |
H24B | 0.2037 | 0.3912 | 0.0099 | 0.071* | |
H24C | 0.2002 | 0.3038 | 0.0430 | 0.071* | |
C25 | 0.0646 (2) | 0.2471 (2) | 0.16264 (13) | 0.0360 (8) | |
H25A | 0.1071 | 0.2007 | 0.1742 | 0.054* | |
H25B | 0.0167 | 0.2182 | 0.1438 | 0.054* | |
H25C | 0.0366 | 0.2785 | 0.1893 | 0.054* | |
C26 | 0.1678 (2) | 0.8616 (3) | 0.16355 (15) | 0.0499 (10) | |
H26A | 0.2164 | 0.8821 | 0.1848 | 0.075* | |
H26B | 0.1303 | 0.9136 | 0.1541 | 0.075* | |
H26C | 0.1952 | 0.8337 | 0.1357 | 0.075* | |
C27 | 0.1895 (3) | 0.7006 (3) | 0.27905 (14) | 0.0493 (10) | |
H27A | 0.2031 | 0.7560 | 0.2614 | 0.074* | |
H27B | 0.2466 | 0.6751 | 0.2914 | 0.074* | |
H27C | 0.1482 | 0.7149 | 0.3051 | 0.074* | |
C28 | 0.2023 (2) | 0.5955 (3) | 0.18550 (14) | 0.0475 (10) | |
H28A | 0.2129 | 0.6531 | 0.1692 | 0.071* | |
H28B | 0.1688 | 0.5541 | 0.1648 | 0.071* | |
H28C | 0.2613 | 0.5684 | 0.1941 | 0.071* | |
C29 | 0.1113 (3) | 0.5080 (2) | 0.27182 (12) | 0.0396 (9) | |
C30 | 0.0450 (3) | 0.5260 (3) | 0.31268 (13) | 0.0506 (10) | |
H30A | −0.0128 | 0.5501 | 0.3004 | 0.076* | |
H30B | 0.0724 | 0.5701 | 0.3342 | 0.076* | |
H30C | 0.0333 | 0.4692 | 0.3294 | 0.076* | |
C31 | 0.2012 (3) | 0.4687 (3) | 0.29134 (15) | 0.0615 (12) | |
H31A | 0.2443 | 0.4585 | 0.2655 | 0.092* | |
H31B | 0.1885 | 0.4110 | 0.3071 | 0.092* | |
H31C | 0.2279 | 0.5114 | 0.3138 | 0.092* | |
C32 | 0.0674 (3) | 0.4383 (2) | 0.23914 (14) | 0.0555 (11) | |
H32A | 0.1078 | 0.4275 | 0.2123 | 0.083* | |
H32B | 0.0083 | 0.4613 | 0.2280 | 0.083* | |
H32C | 0.0579 | 0.3814 | 0.2562 | 0.083* | |
O6 | −0.57989 (14) | 0.64981 (15) | 0.04186 (10) | 0.0421 (6) | |
O9 | −0.21806 (14) | 0.39510 (13) | 0.09896 (8) | 0.0310 (5) | |
O12 | 0.12816 (14) | 0.55628 (14) | 0.03247 (8) | 0.0307 (5) | |
O13 | 0.20723 (13) | 0.42008 (14) | 0.07782 (8) | 0.0310 (5) | |
O14 | 0.11336 (14) | 0.31087 (14) | 0.13442 (8) | 0.0336 (6) | |
O19 | 0.11156 (14) | 0.79672 (14) | 0.18701 (8) | 0.0339 (6) | |
O20 | 0.02891 (14) | 0.65289 (15) | 0.22516 (8) | 0.0312 (5) | |
Si | 0.13378 (6) | 0.61646 (6) | 0.23950 (3) | 0.0320 (2) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N | 0.0205 (13) | 0.0109 (11) | 0.0335 (15) | −0.0003 (10) | −0.0035 (11) | −0.0011 (11) |
C1 | 0.0186 (14) | 0.0141 (13) | 0.0291 (17) | 0.0006 (11) | −0.0005 (12) | 0.0006 (12) |
C2 | 0.0181 (15) | 0.0156 (14) | 0.0257 (16) | −0.0008 (12) | 0.0001 (12) | 0.0013 (12) |
C3 | 0.0199 (15) | 0.0132 (13) | 0.0283 (16) | −0.0011 (12) | 0.0019 (13) | 0.0005 (12) |
C4 | 0.0265 (16) | 0.0163 (14) | 0.0305 (17) | −0.0029 (12) | −0.0001 (13) | −0.0006 (13) |
C5 | 0.0225 (16) | 0.0248 (16) | 0.0348 (19) | −0.0085 (13) | −0.0013 (14) | −0.0005 (14) |
C6 | 0.0176 (15) | 0.0280 (16) | 0.0325 (17) | 0.0013 (13) | −0.0051 (13) | 0.0034 (14) |
C7 | 0.0228 (15) | 0.0174 (14) | 0.0327 (18) | 0.0014 (12) | 0.0005 (13) | 0.0021 (13) |
C8 | 0.0183 (14) | 0.0159 (13) | 0.0268 (16) | −0.0005 (12) | −0.0005 (12) | 0.0020 (12) |
C9 | 0.0230 (15) | 0.0166 (14) | 0.0250 (16) | −0.0013 (12) | 0.0006 (13) | −0.0015 (12) |
C10 | 0.0229 (15) | 0.0146 (14) | 0.0275 (16) | 0.0022 (12) | −0.0018 (13) | −0.0044 (12) |
C11 | 0.0207 (15) | 0.0151 (14) | 0.0319 (17) | 0.0032 (12) | −0.0041 (13) | −0.0004 (13) |
C12 | 0.0245 (15) | 0.0193 (14) | 0.0240 (16) | −0.0039 (12) | −0.0017 (13) | −0.0003 (12) |
C13 | 0.0190 (15) | 0.0231 (15) | 0.0312 (17) | 0.0023 (13) | −0.0035 (13) | −0.0016 (13) |
C14 | 0.0260 (16) | 0.0186 (15) | 0.0282 (16) | 0.0043 (13) | −0.0052 (13) | 0.0000 (13) |
C15 | 0.0253 (16) | 0.0174 (14) | 0.0304 (17) | 0.0001 (13) | 0.0012 (13) | 0.0005 (13) |
C16 | 0.0188 (14) | 0.0133 (13) | 0.0319 (17) | 0.0007 (11) | 0.0006 (13) | −0.0016 (12) |
C17 | 0.0248 (16) | 0.0169 (14) | 0.0304 (17) | −0.0001 (12) | −0.0032 (13) | 0.0027 (13) |
C18 | 0.0243 (16) | 0.0176 (15) | 0.0380 (19) | −0.0054 (13) | 0.0013 (14) | 0.0041 (14) |
C19 | 0.0188 (15) | 0.0201 (15) | 0.0382 (19) | −0.0028 (12) | −0.0008 (14) | −0.0056 (14) |
C20 | 0.0190 (15) | 0.0233 (15) | 0.0258 (16) | 0.0014 (12) | 0.0012 (12) | 0.0018 (13) |
C21 | 0.0180 (14) | 0.0164 (14) | 0.0335 (17) | −0.0002 (12) | 0.0024 (13) | 0.0021 (13) |
C22 | 0.0189 (17) | 0.048 (2) | 0.081 (3) | −0.0053 (16) | 0.0019 (18) | −0.001 (2) |
C23 | 0.0315 (17) | 0.0231 (16) | 0.0351 (18) | −0.0024 (14) | 0.0016 (15) | 0.0066 (14) |
C24 | 0.035 (2) | 0.049 (2) | 0.057 (2) | 0.0111 (18) | 0.0121 (18) | −0.0057 (19) |
C25 | 0.0391 (19) | 0.0236 (16) | 0.045 (2) | 0.0031 (15) | −0.0068 (17) | 0.0126 (15) |
C26 | 0.0295 (19) | 0.053 (2) | 0.067 (3) | −0.0248 (18) | −0.0098 (18) | 0.014 (2) |
C27 | 0.045 (2) | 0.045 (2) | 0.058 (3) | −0.0024 (18) | −0.0234 (19) | −0.0098 (19) |
C28 | 0.039 (2) | 0.045 (2) | 0.059 (3) | 0.0053 (18) | 0.0051 (19) | −0.0011 (19) |
C29 | 0.054 (2) | 0.0319 (18) | 0.0331 (19) | 0.0051 (17) | −0.0076 (17) | −0.0033 (15) |
C30 | 0.074 (3) | 0.041 (2) | 0.037 (2) | 0.003 (2) | 0.001 (2) | 0.0055 (17) |
C31 | 0.080 (3) | 0.050 (2) | 0.055 (3) | 0.025 (2) | −0.019 (2) | 0.002 (2) |
C32 | 0.084 (3) | 0.033 (2) | 0.049 (3) | −0.010 (2) | −0.002 (2) | 0.0003 (18) |
O6 | 0.0171 (11) | 0.0344 (13) | 0.0746 (19) | −0.0019 (10) | −0.0098 (12) | 0.0069 (12) |
O9 | 0.0255 (11) | 0.0141 (10) | 0.0535 (15) | −0.0020 (9) | 0.0032 (10) | 0.0003 (10) |
O12 | 0.0216 (11) | 0.0256 (11) | 0.0449 (14) | 0.0002 (9) | 0.0028 (10) | 0.0101 (10) |
O13 | 0.0187 (11) | 0.0336 (12) | 0.0408 (13) | 0.0063 (9) | 0.0008 (10) | 0.0010 (10) |
O14 | 0.0279 (12) | 0.0273 (12) | 0.0456 (14) | 0.0073 (10) | −0.0034 (10) | 0.0122 (10) |
O19 | 0.0231 (11) | 0.0331 (12) | 0.0454 (14) | −0.0137 (10) | −0.0064 (10) | −0.0003 (11) |
O20 | 0.0241 (11) | 0.0352 (12) | 0.0345 (13) | −0.0046 (10) | −0.0053 (10) | 0.0069 (10) |
Si | 0.0273 (5) | 0.0311 (5) | 0.0375 (5) | 0.0005 (4) | −0.0087 (4) | −0.0031 (4) |
N—H | 0.83 (3) | C29—C31 | 1.539 (5) |
N—C1 | 1.364 (4) | C29—Si | 1.875 (4) |
N—C8 | 1.384 (4) | O20—Si | 1.673 (2) |
N—O9i | 2.922 (3) | N—H | 0.83 (3) |
C1—C2 | 1.392 (4) | N—H | 0.83 (3) |
C1—C16 | 1.478 (4) | C4—H4A | 0.95 |
C2—C3 | 1.442 (4) | C5—H5A | 0.95 |
C2—C9 | 1.464 (4) | C7—H7A | 0.95 |
C3—C4 | 1.401 (4) | C11—H11A | 0.95 |
C3—C8 | 1.414 (4) | C15—H15A | 0.95 |
C4—C5 | 1.370 (4) | C17—H17A | 0.95 |
C5—C6 | 1.403 (4) | C18—H18A | 0.95 |
C6—O6 | 1.376 (3) | C21—H21A | 0.95 |
C6—C7 | 1.377 (4) | C22—H22A | 0.98 |
C7—C8 | 1.388 (4) | C22—H22B | 0.98 |
C9—O9 | 1.233 (3) | C22—H22C | 0.98 |
C9—C10 | 1.502 (4) | C23—H23A | 0.98 |
C10—C11 | 1.386 (4) | C23—H23B | 0.98 |
C10—C15 | 1.395 (4) | C23—H23C | 0.98 |
C11—C12 | 1.391 (4) | C24—H24A | 0.98 |
C12—O12 | 1.362 (3) | C24—H24B | 0.98 |
C12—C13 | 1.395 (4) | C24—H24C | 0.98 |
C13—O13 | 1.378 (3) | C25—H25A | 0.98 |
C13—C14 | 1.398 (4) | C25—H25B | 0.98 |
C14—O14 | 1.360 (3) | C25—H25C | 0.98 |
C14—C15 | 1.391 (4) | C26—H26A | 0.98 |
C16—C17 | 1.388 (4) | C26—H26B | 0.98 |
C16—C21 | 1.396 (4) | C26—H26C | 0.98 |
C17—C18 | 1.389 (4) | C27—H27A | 0.98 |
C18—C19 | 1.381 (4) | C27—H27B | 0.98 |
C19—O19 | 1.362 (3) | C27—H27C | 0.98 |
C19—C20 | 1.401 (4) | C28—H28A | 0.98 |
C20—O20 | 1.368 (4) | C28—H28B | 0.98 |
C20—C21 | 1.376 (4) | C28—H28C | 0.98 |
C22—O6 | 1.429 (4) | C30—H30A | 0.98 |
C23—O12 | 1.430 (3) | C30—H30B | 0.98 |
C24—O13 | 1.430 (4) | C30—H30C | 0.98 |
C25—O14 | 1.429 (4) | C31—H31A | 0.98 |
C26—O19 | 1.427 (4) | C31—H31B | 0.98 |
C27—Si | 1.864 (3) | C31—H31C | 0.98 |
C28—Si | 1.863 (4) | C32—H32A | 0.98 |
C29—C32 | 1.530 (5) | C32—H32B | 0.98 |
C29—C30 | 1.538 (5) | C32—H32C | 0.98 |
H—N—C1 | 124 (2) | C4—C5—H5A | 119.5 |
H—N—C8 | 124 (2) | C6—C5—H5A | 119.5 |
C1—N—C8 | 110.2 (2) | C6—C7—H7A | 121.3 |
N—C1—C2 | 109.0 (2) | C8—C7—H7A | 121.3 |
N—C1—C16 | 117.9 (2) | C10—C11—H11A | 120.2 |
C2—C1—C16 | 132.8 (2) | C12—C11—H11A | 120.2 |
C1—C2—C3 | 106.6 (2) | C14—C15—H15A | 120.1 |
C1—C2—C9 | 130.7 (3) | C10—C15—H15A | 120.1 |
C3—C2—C9 | 122.7 (2) | C16—C17—H17A | 119.6 |
C4—C3—C8 | 117.4 (3) | C18—C17—H17A | 119.6 |
C4—C3—C2 | 135.6 (3) | C19—C18—H18A | 119.9 |
C8—C3—C2 | 107.0 (2) | C17—C18—H18A | 119.9 |
C5—C4—C3 | 120.0 (3) | C20—C21—H21A | 119.6 |
C4—C5—C6 | 121.1 (3) | C16—C21—H21A | 119.6 |
O6—C6—C7 | 115.5 (3) | O6—C22—H22A | 109.5 |
O6—C6—C5 | 123.6 (3) | O6—C22—H22B | 109.5 |
C7—C6—C5 | 120.9 (3) | H22A—C22—H22B | 109.5 |
C6—C7—C8 | 117.5 (3) | O6—C22—H22C | 109.5 |
N—C8—C7 | 129.7 (2) | H22A—C22—H22C | 109.5 |
N—C8—C3 | 107.2 (2) | H22B—C22—H22C | 109.5 |
C7—C8—C3 | 123.1 (3) | O12—C23—H23A | 109.5 |
O9—C9—C2 | 119.5 (3) | O12—C23—H23B | 109.5 |
O9—C9—C10 | 118.5 (3) | H23A—C23—H23B | 109.5 |
C2—C9—C10 | 121.8 (2) | O12—C23—H23C | 109.5 |
C11—C10—C15 | 120.9 (3) | H23A—C23—H23C | 109.5 |
C11—C10—C9 | 121.4 (3) | H23B—C23—H23C | 109.5 |
C15—C10—C9 | 117.3 (3) | O13—C24—H24A | 109.5 |
C10—C11—C12 | 119.5 (3) | O13—C24—H24B | 109.5 |
O12—C12—C11 | 125.1 (3) | H24A—C24—H24B | 109.5 |
O12—C12—C13 | 114.9 (3) | O13—C24—H24C | 109.5 |
C11—C12—C13 | 120.0 (3) | H24A—C24—H24C | 109.5 |
O13—C13—C12 | 119.9 (3) | H24B—C24—H24C | 109.5 |
O13—C13—C14 | 119.7 (3) | O14—C25—H25A | 109.5 |
C12—C13—C14 | 120.4 (3) | O14—C25—H25B | 109.5 |
O14—C14—C15 | 125.4 (3) | H25A—C25—H25B | 109.5 |
O14—C14—C13 | 115.2 (3) | O14—C25—H25C | 109.5 |
C15—C14—C13 | 119.4 (3) | H25A—C25—H25C | 109.5 |
C14—C15—C10 | 119.8 (3) | H25B—C25—H25C | 109.5 |
C17—C16—C21 | 118.8 (3) | O19—C26—H26A | 109.5 |
C17—C16—C1 | 120.3 (3) | O19—C26—H26B | 109.5 |
C21—C16—C1 | 120.9 (3) | H26A—C26—H26B | 109.5 |
C16—C17—C18 | 120.8 (3) | O19—C26—H26C | 109.5 |
C19—C18—C17 | 120.1 (3) | H26A—C26—H26C | 109.5 |
O19—C19—C18 | 125.5 (3) | H26B—C26—H26C | 109.5 |
O19—C19—C20 | 115.0 (3) | Si—C27—H27A | 109.5 |
C18—C19—C20 | 119.5 (3) | Si—C27—H27B | 109.5 |
O20—C20—C21 | 119.3 (3) | H27A—C27—H27B | 109.5 |
O20—C20—C19 | 120.5 (3) | Si—C27—H27C | 109.5 |
C21—C20—C19 | 120.1 (3) | H27A—C27—H27C | 109.5 |
C20—C21—C16 | 120.8 (3) | H27B—C27—H27C | 109.5 |
C32—C29—C30 | 108.3 (3) | Si—C28—H28A | 109.5 |
C32—C29—C31 | 108.9 (3) | Si—C28—H28B | 109.5 |
C30—C29—C31 | 109.1 (3) | H28A—C28—H28B | 109.5 |
C32—C29—Si | 110.3 (2) | Si—C28—H28C | 109.5 |
C30—C29—Si | 109.6 (2) | H28A—C28—H28C | 109.5 |
C31—C29—Si | 110.5 (3) | H28B—C28—H28C | 109.5 |
C6—O6—C22 | 117.4 (2) | C29—C30—H30A | 109.5 |
C12—O12—C23 | 117.0 (2) | C29—C30—H30B | 109.5 |
C13—O13—C24 | 112.5 (2) | H30A—C30—H30B | 109.5 |
C14—O14—C25 | 117.7 (2) | C29—C30—H30C | 109.5 |
C19—O19—C26 | 117.2 (3) | H30A—C30—H30C | 109.5 |
C20—O20—Si | 128.80 (19) | H30B—C30—H30C | 109.5 |
O20—Si—C28 | 110.01 (15) | C29—C31—H31A | 109.5 |
O20—Si—C27 | 109.48 (15) | C29—C31—H31B | 109.5 |
C28—Si—C27 | 112.12 (18) | H31A—C31—H31B | 109.5 |
O20—Si—C29 | 103.55 (14) | C29—C31—H31C | 109.5 |
C28—Si—C29 | 111.06 (17) | H31A—C31—H31C | 109.5 |
C27—Si—C29 | 110.29 (17) | H31B—C31—H31C | 109.5 |
H—N—C1 | 124 (2) | C29—C32—H32A | 109.5 |
H—N—C8 | 124 (2) | C29—C32—H32B | 109.5 |
C1—N—H | 124 (2) | H32A—C32—H32B | 109.5 |
C8—N—H | 124 (2) | C29—C32—H32C | 109.5 |
C5—C4—H4A | 120.0 | H32A—C32—H32C | 109.5 |
C3—C4—H4A | 120.0 | H32B—C32—H32C | 109.5 |
H—N—C1—C2 | 170 (3) | O13—C13—C14—C15 | −179.5 (3) |
C8—N—C1—C2 | 2.5 (3) | C12—C13—C14—C15 | 2.5 (4) |
H—N—C1—C16 | −5 (3) | O14—C14—C15—C10 | 179.7 (3) |
C8—N—C1—C16 | −172.3 (3) | C13—C14—C15—C10 | −1.1 (4) |
N—C1—C2—C3 | −3.6 (3) | C11—C10—C15—C14 | −1.0 (4) |
C16—C1—C2—C3 | 170.1 (3) | C9—C10—C15—C14 | 172.2 (3) |
N—C1—C2—C9 | 176.5 (3) | N—C1—C16—C17 | −49.2 (4) |
C16—C1—C2—C9 | −9.8 (6) | C2—C1—C16—C17 | 137.5 (3) |
C1—C2—C3—C4 | −176.7 (3) | N—C1—C16—C21 | 128.1 (3) |
C9—C2—C3—C4 | 3.3 (5) | C2—C1—C16—C21 | −45.2 (5) |
C1—C2—C3—C8 | 3.4 (3) | C21—C16—C17—C18 | −0.7 (4) |
C9—C2—C3—C8 | −176.7 (3) | C1—C16—C17—C18 | 176.7 (3) |
C8—C3—C4—C5 | −2.8 (4) | C16—C17—C18—C19 | −0.4 (4) |
C2—C3—C4—C5 | 177.2 (3) | C17—C18—C19—O19 | −177.5 (3) |
C3—C4—C5—C6 | 2.4 (5) | C17—C18—C19—C20 | 1.0 (4) |
C4—C5—C6—O6 | 179.0 (3) | O19—C19—C20—O20 | 0.7 (4) |
C4—C5—C6—C7 | −0.3 (5) | C18—C19—C20—O20 | −178.0 (3) |
O6—C6—C7—C8 | 179.3 (3) | O19—C19—C20—C21 | 178.1 (3) |
C5—C6—C7—C8 | −1.4 (5) | C18—C19—C20—C21 | −0.6 (4) |
H—N—C8—C7 | 9 (3) | O20—C20—C21—C16 | 176.9 (3) |
C1—N—C8—C7 | 176.4 (3) | C19—C20—C21—C16 | −0.5 (4) |
H—N—C8—C3 | −167 (3) | C17—C16—C21—C20 | 1.1 (4) |
C1—N—C8—C3 | −0.3 (3) | C1—C16—C21—C20 | −176.2 (3) |
C6—C7—C8—N | −175.3 (3) | C7—C6—O6—C22 | −155.2 (3) |
C6—C7—C8—C3 | 0.9 (5) | C5—C6—O6—C22 | 25.4 (5) |
C4—C3—C8—N | 178.1 (3) | C11—C12—O12—C23 | 14.1 (4) |
C2—C3—C8—N | −1.9 (3) | C13—C12—O12—C23 | −167.5 (3) |
C4—C3—C8—C7 | 1.1 (5) | C12—C13—O13—C24 | −88.5 (3) |
C2—C3—C8—C7 | −178.9 (3) | C14—C13—O13—C24 | 93.5 (3) |
C1—C2—C9—O9 | 161.3 (3) | C15—C14—O14—C25 | 3.4 (4) |
C3—C2—C9—O9 | −18.6 (4) | C13—C14—O14—C25 | −175.8 (3) |
C1—C2—C9—C10 | −21.8 (5) | C18—C19—O19—C26 | −13.6 (4) |
C3—C2—C9—C10 | 158.3 (3) | C20—C19—O19—C26 | 167.8 (3) |
O9—C9—C10—C11 | 142.3 (3) | C21—C20—O20—Si | 124.8 (3) |
C2—C9—C10—C11 | −34.6 (4) | C19—C20—O20—Si | −57.9 (4) |
O9—C9—C10—C15 | −30.8 (4) | C20—O20—Si—C28 | −15.4 (3) |
C2—C9—C10—C15 | 152.3 (3) | C20—O20—Si—C27 | 108.2 (3) |
C15—C10—C11—C12 | 1.7 (4) | C20—O20—Si—C29 | −134.2 (3) |
C9—C10—C11—C12 | −171.2 (3) | C32—C29—Si—O20 | 64.1 (3) |
C10—C11—C12—O12 | 178.0 (3) | C30—C29—Si—O20 | −55.1 (3) |
C10—C11—C12—C13 | −0.3 (4) | C31—C29—Si—O20 | −175.4 (2) |
O12—C12—C13—O13 | 1.7 (4) | C32—C29—Si—C28 | −53.9 (3) |
C11—C12—C13—O13 | −179.8 (3) | C30—C29—Si—C28 | −173.1 (3) |
O12—C12—C13—C14 | 179.7 (3) | C31—C29—Si—C28 | 66.6 (3) |
C11—C12—C13—C14 | −1.8 (4) | C32—C29—Si—C27 | −178.8 (3) |
O13—C13—C14—O14 | −0.3 (4) | C30—C29—Si—C27 | 61.9 (3) |
C12—C13—C14—O14 | −178.3 (3) | C31—C29—Si—C27 | −58.3 (3) |
Symmetry code: (i) −x−1/2, y+1/2, z. |
D—H···A | D—H | H···A | D···A | D—H···A |
N—H···O9i | 0.83 (3) | 2.10 (3) | 2.922 (4) | 170 (3) |
C4—H4···O9 | 0.95 | 2.52 | 3.022 (4) | 113 |
C22—H22a···O12ii | 0.98 | 2.53 | 3.224 (4) | 127 |
C26—H26c···O13iii | 0.98 | 2.53 | 3.171 (4) | 123 |
C27—H27a···O19 | 0.98 | 2.58 | 3.194 (4) | 121 |
Symmetry codes: (i) −x−1/2, y+1/2, z; (ii) x−1, y, z; (iii) −x+1/2, y+1/2, z. |
Experimental details
Crystal data | |
Chemical formula | C32H39NO7Si |
Mr | 577.73 |
Crystal system, space group | Orthorhombic, Pbca |
Temperature (K) | 173 |
a, b, c (Å) | 14.596 (1), 14.753 (1), 28.531 (4) |
V (Å3) | 6143.8 (10) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.55 × 0.49 × 0.49 |
Data collection | |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | ψ scan (SHELXTL/PC; Sheldrick, 1995) |
Tmin, Tmax | 0.926, 0.945 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5570, 5335, 3841 |
Rint | 0.017 |
(sin θ/λ)max (Å−1) | 0.594 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.127, 1.08 |
No. of reflections | 5335 |
No. of parameters | 374 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
w = 1/[σ2(Fo2) + (0.0242P)2 + 12.4107P] where P = (Fo2 + 2Fc2)/3 | |
Δρmax, Δρmin (e Å−3) | 0.37, −0.41 |
Computer programs: CAD-4 Software (Enraf-Nonius, 1989), CAD-4 Software, XCAD4 (Harms, 1993), SHELXTL/PC (Sheldrick, 1995), SHELXL97 (Sheldrick, 1997), XP in SHELXTL/PC, SHELXL97.
N—C1 | 1.364 (4) | C20—O20 | 1.368 (4) |
N—C8 | 1.384 (4) | C22—O6 | 1.429 (4) |
C6—O6 | 1.376 (3) | C23—O12 | 1.430 (3) |
C9—O9 | 1.233 (3) | C24—O13 | 1.430 (4) |
C12—O12 | 1.362 (3) | C25—O14 | 1.429 (4) |
C13—O13 | 1.378 (3) | C26—O19 | 1.427 (4) |
C14—O14 | 1.360 (3) | O20—Si | 1.673 (2) |
C19—O19 | 1.362 (3) | ||
C1—N—C8 | 110.2 (2) | O20—C20—C21 | 119.3 (3) |
N—C1—C16 | 117.9 (2) | O20—C20—C19 | 120.5 (3) |
O6—C6—C7 | 115.5 (3) | C6—O6—C22 | 117.4 (2) |
O6—C6—C5 | 123.6 (3) | C12—O12—C23 | 117.0 (2) |
O9—C9—C2 | 119.5 (3) | C13—O13—C24 | 112.5 (2) |
O9—C9—C10 | 118.5 (3) | C14—O14—C25 | 117.7 (2) |
O12—C12—C11 | 125.1 (3) | C19—O19—C26 | 117.2 (3) |
O12—C12—C13 | 114.9 (3) | C20—O20—Si | 128.80 (19) |
O13—C13—C12 | 119.9 (3) | O20—Si—C28 | 110.01 (15) |
O13—C13—C14 | 119.7 (3) | O20—Si—C27 | 109.48 (15) |
O14—C14—C15 | 125.4 (3) | C28—Si—C27 | 112.12 (18) |
O14—C14—C13 | 115.2 (3) | O20—Si—C29 | 103.55 (14) |
O19—C19—C18 | 125.5 (3) | C28—Si—C29 | 111.06 (17) |
O19—C19—C20 | 115.0 (3) | C27—Si—C29 | 110.29 (17) |
C16—C1—C2—C9 | −9.8 (6) | C11—C12—O12—C23 | 14.1 (4) |
C1—C2—C9—C10 | −21.8 (5) | C13—C12—O12—C23 | −167.5 (3) |
C3—C2—C9—C10 | 158.3 (3) | C12—C13—O13—C24 | −88.5 (3) |
O12—C12—C13—O13 | 1.7 (4) | C14—C13—O13—C24 | 93.5 (3) |
O13—C13—C14—O14 | −0.3 (4) | C15—C14—O14—C25 | 3.4 (4) |
N—C1—C16—C17 | −49.2 (4) | C13—C14—O14—C25 | −175.8 (3) |
N—C1—C16—C21 | 128.1 (3) | C18—C19—O19—C26 | −13.6 (4) |
O19—C19—C20—O20 | 0.7 (4) | C20—C19—O19—C26 | 167.8 (3) |
C7—C6—O6—C22 | −155.2 (3) | C21—C20—O20—Si | 124.8 (3) |
C5—C6—O6—C22 | 25.4 (5) | C19—C20—O20—Si | −57.9 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N—H···O9i | .83 (3) | 2.10 (3) | 2.922 (4) | 170 (3) |
C4—H4···O9 | 0.95 | 2.52 | 3.022 (4) | 113 |
C22—H22a···O12ii | 0.98 | 2.53 | 3.224 (4) | 127 |
C26—H26c···O13iii | 0.98 | 2.53 | 3.171 (4) | 123 |
C27—H27a···O19 | 0.98 | 2.58 | 3.194 (4) | 121 |
Symmetry codes: (i) −x−1/2, y+1/2, z; (ii) x−1, y, z; (iii) −x+1/2, y+1/2, z. |
The protein tubulin plays a vital role during mitosis through the process of polymerization and depolymerization. Inhibitors of tubulin polymerization are known to arrest the assembly of tubulin into microtubules, resulting in the disruption of cell division (Hamel, 1996). Recently, it has been established that some of these agents rapidly shut down tumor vasculature, which results in necrosis of the tumor cells (Galbraith et al., 2001; Tozer et al., 1999). Combretastatin A-4(CA-4), (I) (Pettit et al., 1982, 1987, 2000), interacts with the colchicine binding site with a high binding affinity and inhibits the assembly of tubulin into microtubules (Hamel & Lin, 1983), while its corresponding water soluble prodrug, disodium phosphate CA-4P, (II) (Pettit et al., 1998), is inactive with tubulin. It is suggested that the phosphate moiety navigates the molecule in selectively targeting the sites of increased vascularization, as it undergoes dephosphorylation at these sites by the action of endothelial alkaline phosphatases, which release the active form of the drug, CA-4.
Two benzo[b]thiophene analogs, i.e. (III) and (IV), which bear structural features similar to CA-4, demonstrate excellent cytotoxicity and inhibition of tubulin polymerization (Mullica et al., 1998; Pinney et al., 1998, 1999; Flynn et al., 2001). Encouraged by these promising research results, we synthesized an indole variant as both the free phenol (V) (Pinney et al., 2001; Flynn, 2001; during the preparation of this manuscript, we learned that this compound had also been prepared independently by an alternate synthetic route), and its corresponding tert-butyldimethylsilyl ether, (VI), which will be eventually converted to its water-soluble phosphate prodrug form.
In order to unequivocally confirm the molecular structure, as well as gather information paramount for our molecular recognition studies, we have determined the crystal structure of (VI).
Fig. 1 shows the molecular structure of (VI), while selected geometric parameters are presented in Table 1. A l l internuclear distances and angles fall within the range of expected values and are comparable with those found in the related benzo[b]thiophene (III) structure determined by Mullica et al. (1998).
The indole ring is planar within 0.028 Å and forms respective dihedral angles of 49.50 (9) and 46.97 (7)° with the methoxyphenyl and trimethoxybenzoyl moieties. The latter two ring systems are also planar within 0.005 and 0.009 Å, respectively, and exhibit a dihedral angle of 48.93 (10)°, with a centroid-to-centroid separation of 4.36 Å.
The methoxy substituents on the several ring systems are rotated by various intervals to accommodate steric and crystal-packing requirements. Appropriate torsion angles are given in Table 1. Most notably, the methoxy group in position 4 of the 3,4,5-trimethoxybenzoyl component is rotated approximately 92.5° from the least-squares plane of the ring, with the terminal C24 atom extending 1.332 Å from the ring. The remaining substituents on the same group are twisted by 13.3 and 3.8°, respectively, with C23 and C25 protruding by 0.275 and 0.040 Å, respectively, above and below the ring. Elsewhere, the methoxy groups on the TBS–methoxyphenyl (TBS is tert-butyldimethylsiloxy) and methoxyindole moieties are turned 12.9 and 25.1° from their respective ring planes; atoms C26 and C22 project from their corresponding rings by 0.207 and 0.632 Å, respectively.
The supramolecular structure of (VI) consist of corrugated ribbons formed by an infinite linear array of molecules linked by an intermolecular N—H···O hydrogen-bonding interaction. According to Etter's graph-set analysis, this hydrogen-bond system is designated C(6) (Etter et al., 1990; Bernstein et al., 1995) and runs parallel to the b axis of the crystal lattice. Additionally, several other O atoms are involved in multiple close contacts with surrounding H atoms of the various adjacent groups. According to the somewhat liberal definition ascribed by Desiraju & Steiner (1999), these contacts may be classified as weak C—H···O hydrogen bonds; details are included in Table 2.