Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229614027399/qs3041sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229614027399/qs3041Isup2.hkl |
CCDC reference: 1039412
Many natural products have been isolated and found to be effective in the treatment of cancer through chemotherapy. One important member of this class of natural anticancer agents is pacilitaxel, or Taxol. Taxol promotes the assembly of tubulin into stable microtubules and is therefore effective as an antimitotic drug. Baccatin III was isolated from the Pacific yew tree, Taxus brevifolia, and is a precursor to pacilitaxel. Taxol has an extremely complex structure and therefore its efficient synthesis continues to be of current interest. Over the past decade, researchers have reported the cloning and expression of 10-deacetylbaccatin III–10-O-acetyltransferase (Walker & Croteau, 2000). Confirmation of the structure, conformation,and stereochemistry of baccatin III derivatives is important for fostering new synthetic approaches and validating new enzymatic routes for synthetic conversion. We report herein the structure of one such derivative namely 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)-10-deacetyl baccatin III (7,10-di-Troc-DAB)–ethyl acetate–water (1/1/1), (I).
The taxane diterpenoids have attracted the attention of synthetic and medicinal chemists due to their unique structures and significant biological activities in relation to similar classes of compounds during the past 50 years. To date, more than 400 natural taxanes and hundreds of synthetic analogues have been discovered (Appendino, 1995; Ojima et al., 2005). Taxol and docetaxel, the most notable of the taxane diterpenoids, are two of the most widely used drugs in the fight against cancer among a variety of chemotherapeutic agents. Taxol was first isolated from Taxus brevifolia by Wani et al. (1971), who established its structure by chemical and X-ray crystallographic methods, but full details of the X-ray analysis were never published. However, docetaxel is a semisynthetic taxoid and its absolute configuration was established by X-ray analysis (Gueritte-Voegelein et al. 1990). 10-Deacetylbaccatin III, the diterpenoid nucleus of taxol and docetaxel and a more readily available taxane diterpenoid precursor, can be isolated from the needles of Taxus baccata. It should be noted that this is a regenerable source, and harvest does not threaten the survival of the species (Denis et al., 1988). Ho et al. (1987) reported the crystal structures of baccatin analogues Taxusin and Taxusin derivatives. In 1992, the structure elucidation and a study of the reactivity of 14β-hydroxy-10-deacetylbaccatin III were presented (Appendino et al., 1992). Structural modifications of naturally occurring bioactive substances by microbial transformations in a way [not] possible by conventional chemical methods are an important area of natural product chemistry. In our studies, a crystal of 7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)-10-deacetyl baccatin III (7,10-di-Troc-DAB)–ethyl acetate–water (1/1/1), (I), suitable for X-ray diffraction analysis was obtained and its structure elucidated.
Under a nitrogen atmosphere, a solution of 10-deacetylbaccatin III (1.01 g, 2.0 mmol) in dry pyridine (18 ml) was heated at 353 K and 2,2,2-trichloroethyl chloroformate (0.777 g, 3.68 mmol) was added dropwise. After 25 min, the flask was removed from the oil bath and the reaction quenched by the careful addition of a few drops of methanol and pieces of ice [OK or "few drops of ice-cold methanol"?]. The reaction mixture was extracted with CH2Cl2, and the organic phase was washed with dilute HCl and brine. After drying (MgSO4) and removal of the solvent, a semi-solid residue was obtained, which was dissolved in ethyl acetate and recrystalized. 7,10-di-Troc-DAB was obtained as white crystals (yield 1.18 g, 72%) suitable for X-ray analysis.
Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were placed in idealized positions and allowed to ride on their respective parent atom, with C—H = 0.93 (aromatic), 0.96 (CH3) or 0.97 Å (CH2) and N—H = 0.86 Å, and with Uiso(H) = 1.5Ueq(C,N) for methyl and hydroxy H atoms or 1.2Ueq(C,N) otherwise. The H atoms of the water molecules were located in a difference map and were all permitted to ride at fixed O—H distances (0.87 Å) and with Uiso(H) = 1.2Ueq(O). Riding restraints were applied for the methyl and hydroxy groups.
In the crystal of (I), t7,10-di-Troc-DAB exists as a 1:1:1 complex with ethyl acetate and water, the solvents from which the crystal was grown. In general, the tetracyclic ring structure is very compact and relatively rigid. As shown in Fig. 2, the core tetracyclic ring system has a rigid structure. The central eight-membered ring B (see Scheme) adopts the most stable boat–chair conformation, which is essentially identical to baccatin analogues and baccatin derivatives (Gao et al., 1987). The six-membered ring C is trans-fused to ring B with one common bond (C3–C8); atoms C5 and C8 deviate by 0.014 (5) and 0.785 (4) Å, respectively, from the mean plane of the other four atoms, viz. C3, C4, C6 and C7. The torsion angles C3—C4—C6—C7 [-8.5 (6)°], C4—C3—C7—C8 [-129.5 (7)°] and C4—C7—C6—C5 [3.0 (8)°] likewise suggest that atoms C3, C4, C6 and C7 are not coplanar, so the conformation of ring C is a distorted chair with atom C5 nearly coplanar. In contrast, the other six-membered ring, A, adjacent to eight-membered ring B is a nearly perfect boat, with atoms C13 and C15 above the plane [0.390 (5) and 0.697 (5) Å, respectively] of atoms C1, C11, C12 and C14. It is nearly perfect since C13 and C15 are not equal. The O10 hydroxy group on C13 is oriented towards the concavity of the molecule, not unlike the conformation found in a derivative of 10-deacetylbaccatin III studied by X-ray crystallography (Gueritte-Voegelein et al., 1990).
No intramolecular hydrogen bonds are found. However, the structure does display four intermolecular hydrogen bonds and three kinds of noncovalent interaction, which contribute significantly to the stability of the crystal lattice. As shown in Table 2, water atom O17 forms one intermolecular hydrogen bond with O9 and one intermolecular hydrogen bond with O1. Ethyl acetate atom O15 is involved, as accptor, in an intermolecular hydrogen bond with atom O9 of 7,10-diTroc-DAB at C1. The O···O distance of this hydrogen bond [2.824 (5) Å] is shorter than the O17···O9 [3.079 (5) Å] and O17···O1 [3.260 (5) Å] distances, but is still reasonable. Likewise, the hydrogen bond between atoms O10 and O17, similar to O9···O15, with very similar H···A and D···A distances, is in good agreement with the value of 2.800 Å reported for 14β-hydroxy-10-deacetylbaccatin III (Appendino et al., 1992).
Halogen bonding (XB) refers to the noncovalent interaction of general structure DX···A between halogen-bearing compounds (DX = XB donor, where X = Cl, Br, I) and nucleophiles (A = XB acceptor) (Politzer et al., 2007; Clark et al., 2007). Since Hassel and Hvoslef first observed XB in cocrystal structures of 1,4-dioxane and Br2 in 1954 (Politzer et al., 2007), it has been widely used in crystal engineering and solid-state supramolecular chemistry (Desiraju, 1995; Metrangolo & Resnati, 2001; Sun et al., 2006). Molecules are held together by another noncovalent interaction of the O8···Cl12 halogen bond; the interatomic distance of 3.037 (5) Å is in agreement with the analysis of halogen bonding in protein–ligand interactions (Hardegger et al., 2011). The agreement was also found in the molecular complex of CF3Cl and H2O, where the distance between the Cl and O atoms was estimated to be 3.028 Å versus 2.982 Å obtained by ab initio calculations (Evangelisti et al., 2011). It was noted that two intramolecular O···O interactions also occur in the crystal. The unique feature of complex (I) is the O1···O12 [2.950 (4) Å] and O3···O14 [2.956 (6) Å] intramolecular contacts, which are in the middle of O10···O17 [2.792 (5) Å] and O17···O9 [3.099 (6) Å] O17···O1 [3.217 (5) Å] range of distances in the hydrogen-bonded fragment.
Molecules of compound (I) are linked into chains by weak C···O hydrogen-bond and Cl···O halogen-bond contacts, viewed along the a axis (Fig. 4). In short, hydrogen bonds and noncovalent interactions also contribute significantly to the stability of the crystal lattice. In addition, the title compound is a chiral compound, and the absolute stereochemistry assignment is unambiguous. The Flack parameter is -0.04 (6). This suggests the assignment of the chirality at each of the chiral centers as C1S, C2S, C3R, C4S, C5R, C7S, C8S, C10R and C13S.
Compound (I) displayed good biological activity and the structure–activity relationship of the chemical scaffold core has been determined through the analysis of many studies, as shown in Fig. 5. While compound (I) was synthesized through chemical transformation from 10-deacetyl baccatin III, there are enzymes that also react with these molecules, like transferases. Interestingly enough, the biosynthetic pathway strongly depends upon the conformation of the precursers, so structural studies like that of compound (I) presented here can shed light on the mechanisms of these transferases and the biosynthetic evolution of these structurally complex molecules.
Data collection: APEX2 (Bruker, 2008); cell refinement: 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: Mercury (Macrae et al., 2006).
C34H38Cl6O14·C4H8O2·H2O | F(000) = 2080 |
Mr = 1001.47 | Dx = 1.444 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 2132 reflections |
a = 14.7029 (12) Å | θ = 2.5–17.8° |
b = 16.6256 (14) Å | µ = 0.44 mm−1 |
c = 18.8428 (15) Å | T = 296 K |
V = 4606.0 (7) Å3 | Block, colorless |
Z = 4 | 0.45 × 0.42 × 0.40 mm |
Bruker APEXII CCD diffractometer | 8208 independent reflections |
Radiation source: fine-focus sealed tube | 5474 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.070 |
ϕ and ω scans | θmax = 25.1°, θmin = 1.6° |
Absorption correction: multi-scan (REQAB; Jacobson, 1998) | h = −16→17 |
Tmin = 0.826, Tmax = 0.843 | k = −19→19 |
23553 measured reflections | l = −17→22 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.053 | w = 1/[σ2(Fo2) + (0.0436P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.115 | (Δ/σ)max = 0.001 |
S = 0.98 | Δρmax = 0.30 e Å−3 |
8208 reflections | Δρmin = −0.22 e Å−3 |
560 parameters | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0028 (3) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), 3609 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.04 (6) |
C34H38Cl6O14·C4H8O2·H2O | V = 4606.0 (7) Å3 |
Mr = 1001.47 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 14.7029 (12) Å | µ = 0.44 mm−1 |
b = 16.6256 (14) Å | T = 296 K |
c = 18.8428 (15) Å | 0.45 × 0.42 × 0.40 mm |
Bruker APEXII CCD diffractometer | 8208 independent reflections |
Absorption correction: multi-scan (REQAB; Jacobson, 1998) | 5474 reflections with I > 2σ(I) |
Tmin = 0.826, Tmax = 0.843 | Rint = 0.070 |
23553 measured reflections |
R[F2 > 2σ(F2)] = 0.053 | H-atom parameters constrained |
wR(F2) = 0.115 | Δρmax = 0.30 e Å−3 |
S = 0.98 | Δρmin = −0.22 e Å−3 |
8208 reflections | Absolute structure: Flack (1983), 3609 Friedel pairs |
560 parameters | Absolute structure parameter: −0.04 (6) |
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 | ||
Cl1 | 0.45710 (8) | 0.39676 (8) | 1.07198 (6) | 0.0574 (3) | |
Cl2 | 0.32384 (8) | 0.52020 (9) | 1.04635 (7) | 0.0663 (4) | |
Cl3 | 0.47888 (11) | 0.55326 (9) | 1.13566 (6) | 0.0781 (5) | |
Cl4 | 0.16971 (12) | 0.74382 (10) | 1.06871 (8) | 0.0939 (6) | |
Cl5 | 0.21745 (10) | 0.86644 (8) | 0.96796 (8) | 0.0728 (5) | |
Cl6 | 0.07996 (9) | 0.74944 (10) | 0.93393 (9) | 0.0839 (5) | |
O1 | 0.46529 (17) | 0.49094 (16) | 0.93568 (13) | 0.0365 (7) | |
O2 | 0.5847 (2) | 0.5445 (2) | 0.87752 (16) | 0.0612 (10) | |
O3 | 0.47014 (17) | 0.47830 (16) | 0.82246 (13) | 0.0345 (7) | |
O4 | 0.5596 (2) | 0.34214 (16) | 0.62594 (15) | 0.0448 (8) | |
O5 | 0.64362 (17) | 0.50854 (17) | 0.57182 (15) | 0.0382 (7) | |
O6 | 0.70100 (19) | 0.5507 (2) | 0.67610 (18) | 0.0516 (8) | |
O7 | 0.48375 (18) | 0.53226 (16) | 0.50120 (13) | 0.0364 (7) | |
O8 | 0.3530 (2) | 0.4758 (2) | 0.46317 (17) | 0.0593 (9) | |
O9 | 0.3769 (2) | 0.66053 (19) | 0.48867 (14) | 0.0482 (8) | |
H9 | 0.4072 | 0.6774 | 0.4553 | 0.072* | |
O10 | 0.66200 (19) | 0.7436 (2) | 0.59069 (17) | 0.0611 (10) | |
H10 | 0.6852 | 0.7830 | 0.6096 | 0.092* | |
O11 | 0.34846 (18) | 0.70530 (16) | 0.78068 (14) | 0.0384 (7) | |
O12 | 0.3934 (2) | 0.6456 (2) | 0.88308 (15) | 0.0551 (9) | |
O13 | 0.2697 (2) | 0.72537 (17) | 0.87572 (15) | 0.0460 (8) | |
O14 | 0.30866 (17) | 0.55455 (19) | 0.75760 (16) | 0.0454 (8) | |
O15 | 0.4523 (4) | 0.7217 (4) | 0.3618 (2) | 0.157 (3) | |
O16 | 0.5060 (3) | 0.6814 (3) | 0.2612 (2) | 0.1055 (16) | |
C1 | 0.4330 (3) | 0.6562 (2) | 0.55093 (19) | 0.0316 (10) | |
C2 | 0.4413 (3) | 0.5639 (2) | 0.56530 (19) | 0.0306 (9) | |
H2 | 0.3800 | 0.5413 | 0.5692 | 0.037* | |
C3 | 0.4989 (2) | 0.5342 (2) | 0.63038 (18) | 0.0272 (9) | |
H3 | 0.5347 | 0.5808 | 0.6457 | 0.033* | |
C4 | 0.5692 (3) | 0.4686 (2) | 0.6091 (2) | 0.0309 (10) | |
C5 | 0.6032 (3) | 0.4074 (2) | 0.6642 (2) | 0.0346 (10) | |
H5 | 0.6696 | 0.4022 | 0.6619 | 0.042* | |
C6 | 0.5721 (3) | 0.4145 (3) | 0.7402 (2) | 0.0379 (11) | |
H6A | 0.6250 | 0.4153 | 0.7709 | 0.045* | |
H6B | 0.5364 | 0.3674 | 0.7523 | 0.045* | |
C7 | 0.5156 (3) | 0.4892 (2) | 0.75415 (19) | 0.0317 (9) | |
H7 | 0.5565 | 0.5356 | 0.7575 | 0.038* | |
C8 | 0.4420 (3) | 0.5073 (2) | 0.6975 (2) | 0.0290 (9) | |
C9 | 0.3810 (3) | 0.5734 (2) | 0.7324 (2) | 0.0311 (10) | |
C10 | 0.4167 (3) | 0.6584 (2) | 0.7431 (2) | 0.0332 (10) | |
H10A | 0.4704 | 0.6549 | 0.7738 | 0.040* | |
C11 | 0.4451 (3) | 0.6999 (2) | 0.6761 (2) | 0.0314 (10) | |
C12 | 0.5308 (3) | 0.7261 (2) | 0.6688 (2) | 0.0355 (10) | |
C13 | 0.5655 (3) | 0.7492 (3) | 0.5956 (2) | 0.0448 (11) | |
H13 | 0.5473 | 0.8048 | 0.5855 | 0.054* | |
C14 | 0.5273 (3) | 0.6947 (3) | 0.5378 (2) | 0.0400 (11) | |
H14A | 0.5706 | 0.6517 | 0.5298 | 0.048* | |
H14B | 0.5238 | 0.7258 | 0.4943 | 0.048* | |
C15 | 0.3816 (3) | 0.7014 (2) | 0.6108 (2) | 0.0348 (10) | |
C16 | 0.3627 (3) | 0.7890 (3) | 0.5880 (2) | 0.0487 (12) | |
H16A | 0.3320 | 0.7892 | 0.5430 | 0.073* | |
H16B | 0.4192 | 0.8176 | 0.5838 | 0.073* | |
H16C | 0.3251 | 0.8148 | 0.6228 | 0.073* | |
C17 | 0.2865 (3) | 0.6643 (3) | 0.6226 (2) | 0.0464 (12) | |
H17A | 0.2584 | 0.6888 | 0.6631 | 0.070* | |
H20D | 0.2925 | 0.6075 | 0.6305 | 0.070* | |
H18D | 0.2495 | 0.6734 | 0.5813 | 0.070* | |
C18 | 0.5997 (3) | 0.7319 (3) | 0.7285 (2) | 0.0486 (12) | |
H18A | 0.5684 | 0.7366 | 0.7731 | 0.073* | |
H18B | 0.6375 | 0.7783 | 0.7215 | 0.073* | |
H18C | 0.6368 | 0.6844 | 0.7289 | 0.073* | |
C19 | 0.3823 (3) | 0.4340 (2) | 0.6832 (2) | 0.0362 (10) | |
H19A | 0.4193 | 0.3908 | 0.6656 | 0.054* | |
H19B | 0.3369 | 0.4475 | 0.6487 | 0.054* | |
H19C | 0.3533 | 0.4175 | 0.7265 | 0.054* | |
C20 | 0.5377 (3) | 0.3945 (2) | 0.5674 (2) | 0.0389 (10) | |
H20A | 0.4734 | 0.3953 | 0.5559 | 0.047* | |
H20B | 0.5738 | 0.3841 | 0.5253 | 0.047* | |
C21 | 0.7058 (3) | 0.5467 (3) | 0.6127 (3) | 0.0449 (12) | |
C22 | 0.7808 (3) | 0.5823 (3) | 0.5686 (3) | 0.0629 (15) | |
H22A | 0.7773 | 0.6399 | 0.5705 | 0.094* | |
H22B | 0.7745 | 0.5648 | 0.5203 | 0.094* | |
H22C | 0.8386 | 0.5650 | 0.5867 | 0.094* | |
C23 | 0.4325 (4) | 0.4918 (3) | 0.4540 (2) | 0.0438 (12) | |
C24 | 0.4857 (4) | 0.4674 (3) | 0.3912 (2) | 0.0581 (14) | |
C25 | 0.4390 (5) | 0.4371 (3) | 0.3332 (3) | 0.087 (2) | |
H25 | 0.3757 | 0.4354 | 0.3331 | 0.105* | |
C26 | 0.4882 (9) | 0.4090 (5) | 0.2749 (4) | 0.137 (4) | |
H26 | 0.4573 | 0.3866 | 0.2366 | 0.164* | |
C27 | 0.5804 (10) | 0.4137 (6) | 0.2730 (5) | 0.162 (6) | |
H27 | 0.6123 | 0.3967 | 0.2331 | 0.194* | |
C28 | 0.6257 (6) | 0.4436 (4) | 0.3304 (4) | 0.121 (3) | |
H28 | 0.6889 | 0.4453 | 0.3300 | 0.145* | |
C29 | 0.5791 (5) | 0.4714 (3) | 0.3891 (3) | 0.0780 (18) | |
H29 | 0.6110 | 0.4929 | 0.4273 | 0.094* | |
C30 | 0.5136 (3) | 0.5093 (3) | 0.8778 (2) | 0.0386 (10) | |
C31 | 0.4953 (3) | 0.5319 (3) | 0.99803 (19) | 0.0420 (11) | |
H31A | 0.4865 | 0.5894 | 0.9927 | 0.050* | |
H31B | 0.5595 | 0.5219 | 1.0058 | 0.050* | |
C32 | 0.4407 (3) | 0.5012 (3) | 1.0603 (2) | 0.0449 (11) | |
C33 | 0.3426 (3) | 0.6871 (3) | 0.8494 (2) | 0.0409 (11) | |
C34 | 0.2575 (3) | 0.7095 (3) | 0.9504 (2) | 0.0535 (13) | |
H34A | 0.3141 | 0.7185 | 0.9756 | 0.064* | |
H34B | 0.2394 | 0.6540 | 0.9575 | 0.064* | |
C35 | 0.1848 (3) | 0.7652 (3) | 0.9783 (2) | 0.0538 (13) | |
C36 | 0.3518 (4) | 0.6914 (6) | 0.2637 (4) | 0.149 (4) | |
H36A | 0.3335 | 0.6360 | 0.2642 | 0.224* | |
H36B | 0.3594 | 0.7090 | 0.2155 | 0.224* | |
H36C | 0.3061 | 0.7236 | 0.2864 | 0.224* | |
C37 | 0.4383 (5) | 0.7002 (5) | 0.3019 (4) | 0.099 (2) | |
C38 | 0.5963 (5) | 0.6867 (6) | 0.2964 (5) | 0.150 (4) | |
H38A | 0.6126 | 0.7427 | 0.3032 | 0.180* | |
H38B | 0.5935 | 0.6611 | 0.3426 | 0.180* | |
C39 | 0.6606 (5) | 0.6495 (5) | 0.2554 (4) | 0.124 (3) | |
H39A | 0.6461 | 0.5934 | 0.2511 | 0.186* | |
H39B | 0.7192 | 0.6553 | 0.2772 | 0.186* | |
H39C | 0.6615 | 0.6737 | 0.2092 | 0.186* | |
H17D | 0.6749 | 0.9256 | 0.5910 | 0.149* | |
H17E | 0.7575 | 0.8891 | 0.5773 | 0.149* | |
O17 | 0.7233 (2) | 0.9006 (2) | 0.6083 (2) | 0.0931 (13) |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0728 (8) | 0.0496 (8) | 0.0498 (7) | 0.0017 (7) | 0.0000 (7) | 0.0074 (6) |
Cl2 | 0.0498 (7) | 0.0778 (10) | 0.0713 (9) | 0.0094 (7) | 0.0164 (7) | 0.0136 (7) |
Cl3 | 0.1216 (12) | 0.0794 (10) | 0.0334 (7) | −0.0244 (10) | 0.0011 (8) | −0.0119 (6) |
Cl4 | 0.1362 (14) | 0.0831 (12) | 0.0625 (9) | −0.0106 (10) | 0.0569 (10) | −0.0013 (9) |
Cl5 | 0.0825 (9) | 0.0360 (7) | 0.0998 (11) | −0.0083 (7) | 0.0446 (9) | −0.0064 (7) |
Cl6 | 0.0627 (8) | 0.0750 (11) | 0.1141 (12) | −0.0064 (8) | 0.0251 (9) | −0.0110 (10) |
O1 | 0.0414 (15) | 0.0447 (18) | 0.0235 (14) | −0.0093 (14) | −0.0010 (13) | 0.0030 (13) |
O2 | 0.0459 (19) | 0.097 (3) | 0.0413 (19) | −0.0285 (19) | 0.0061 (16) | −0.0100 (19) |
O3 | 0.0381 (15) | 0.0422 (18) | 0.0231 (14) | −0.0071 (14) | 0.0002 (13) | 0.0017 (13) |
O4 | 0.0614 (19) | 0.0298 (17) | 0.0433 (17) | 0.0031 (15) | −0.0031 (16) | 0.0002 (14) |
O5 | 0.0350 (15) | 0.0388 (18) | 0.0407 (16) | 0.0010 (14) | 0.0066 (14) | −0.0003 (15) |
O6 | 0.0451 (18) | 0.060 (2) | 0.049 (2) | −0.0057 (17) | −0.0026 (17) | −0.0077 (18) |
O7 | 0.0438 (16) | 0.0350 (17) | 0.0305 (15) | 0.0051 (14) | 0.0024 (13) | −0.0018 (13) |
O8 | 0.055 (2) | 0.061 (2) | 0.062 (2) | −0.0007 (19) | −0.0129 (18) | −0.0138 (18) |
O9 | 0.061 (2) | 0.052 (2) | 0.0320 (17) | 0.0112 (17) | −0.0081 (15) | 0.0047 (15) |
O10 | 0.0412 (18) | 0.063 (2) | 0.079 (2) | −0.0066 (17) | 0.0178 (17) | −0.0120 (19) |
O11 | 0.0471 (17) | 0.0361 (18) | 0.0320 (16) | 0.0137 (14) | 0.0048 (14) | −0.0057 (14) |
O12 | 0.069 (2) | 0.058 (2) | 0.0385 (19) | 0.0259 (19) | 0.0062 (17) | 0.0019 (17) |
O13 | 0.0565 (19) | 0.0383 (19) | 0.0433 (18) | 0.0111 (16) | 0.0163 (16) | 0.0027 (15) |
O14 | 0.0346 (16) | 0.0442 (19) | 0.057 (2) | −0.0007 (15) | 0.0176 (15) | −0.0047 (16) |
O15 | 0.195 (6) | 0.227 (7) | 0.048 (3) | −0.074 (5) | 0.014 (3) | −0.009 (4) |
O16 | 0.069 (3) | 0.156 (5) | 0.092 (3) | −0.007 (3) | 0.015 (3) | −0.045 (3) |
C1 | 0.042 (2) | 0.029 (2) | 0.024 (2) | 0.003 (2) | −0.0041 (19) | 0.0009 (17) |
C2 | 0.035 (2) | 0.029 (2) | 0.028 (2) | 0.0003 (19) | 0.0036 (19) | −0.0059 (19) |
C3 | 0.032 (2) | 0.026 (2) | 0.023 (2) | −0.0011 (18) | 0.0019 (17) | −0.0024 (17) |
C4 | 0.034 (2) | 0.028 (2) | 0.030 (2) | 0.0018 (19) | 0.0034 (19) | 0.0006 (18) |
C5 | 0.038 (2) | 0.029 (2) | 0.037 (2) | 0.007 (2) | −0.003 (2) | 0.0006 (19) |
C6 | 0.042 (2) | 0.036 (3) | 0.036 (2) | 0.008 (2) | 0.004 (2) | 0.005 (2) |
C7 | 0.036 (2) | 0.034 (2) | 0.025 (2) | 0.001 (2) | 0.0056 (18) | 0.0008 (18) |
C8 | 0.033 (2) | 0.020 (2) | 0.034 (2) | 0.0044 (19) | 0.0011 (18) | 0.0028 (17) |
C9 | 0.029 (2) | 0.033 (3) | 0.032 (2) | 0.0019 (19) | −0.0005 (19) | 0.0046 (19) |
C10 | 0.034 (2) | 0.030 (2) | 0.035 (2) | 0.006 (2) | 0.003 (2) | −0.0060 (19) |
C11 | 0.035 (2) | 0.026 (2) | 0.033 (2) | 0.003 (2) | −0.004 (2) | −0.0050 (19) |
C12 | 0.041 (2) | 0.024 (2) | 0.042 (3) | 0.005 (2) | −0.004 (2) | −0.0104 (19) |
C13 | 0.050 (3) | 0.032 (3) | 0.053 (3) | −0.001 (2) | 0.011 (2) | −0.001 (2) |
C14 | 0.053 (3) | 0.032 (3) | 0.035 (2) | −0.002 (2) | 0.013 (2) | 0.003 (2) |
C15 | 0.038 (2) | 0.032 (3) | 0.034 (2) | 0.004 (2) | −0.002 (2) | 0.000 (2) |
C16 | 0.055 (3) | 0.035 (3) | 0.056 (3) | 0.015 (2) | −0.003 (2) | −0.001 (2) |
C17 | 0.045 (3) | 0.045 (3) | 0.049 (3) | 0.003 (2) | −0.002 (2) | −0.003 (2) |
C18 | 0.048 (3) | 0.040 (3) | 0.058 (3) | 0.001 (2) | −0.007 (2) | −0.013 (2) |
C19 | 0.037 (2) | 0.030 (2) | 0.042 (2) | −0.007 (2) | 0.004 (2) | 0.002 (2) |
C20 | 0.053 (3) | 0.031 (2) | 0.033 (2) | 0.008 (2) | 0.000 (2) | −0.003 (2) |
C21 | 0.030 (2) | 0.035 (3) | 0.070 (4) | 0.008 (2) | 0.003 (3) | 0.004 (3) |
C22 | 0.047 (3) | 0.058 (4) | 0.084 (4) | −0.006 (3) | 0.019 (3) | 0.000 (3) |
C23 | 0.069 (3) | 0.035 (3) | 0.028 (2) | 0.007 (3) | −0.009 (2) | −0.002 (2) |
C24 | 0.102 (4) | 0.045 (3) | 0.028 (3) | 0.008 (3) | 0.005 (3) | 0.004 (2) |
C25 | 0.173 (6) | 0.056 (4) | 0.033 (3) | −0.008 (4) | −0.010 (4) | 0.000 (3) |
C26 | 0.306 (14) | 0.074 (5) | 0.030 (4) | −0.036 (9) | 0.018 (7) | −0.005 (3) |
C27 | 0.317 (16) | 0.086 (7) | 0.083 (7) | −0.009 (10) | 0.100 (10) | −0.020 (5) |
C28 | 0.181 (8) | 0.088 (5) | 0.093 (6) | 0.036 (6) | 0.082 (6) | 0.008 (5) |
C29 | 0.111 (5) | 0.073 (4) | 0.050 (3) | 0.015 (4) | 0.027 (4) | 0.000 (3) |
C30 | 0.040 (3) | 0.046 (3) | 0.029 (2) | 0.006 (2) | 0.003 (2) | 0.005 (2) |
C31 | 0.046 (3) | 0.055 (3) | 0.026 (2) | −0.012 (2) | −0.001 (2) | −0.005 (2) |
C32 | 0.052 (3) | 0.050 (3) | 0.033 (2) | −0.003 (2) | 0.003 (2) | −0.003 (2) |
C33 | 0.051 (3) | 0.030 (3) | 0.042 (3) | 0.002 (2) | 0.006 (2) | −0.006 (2) |
C34 | 0.066 (3) | 0.045 (3) | 0.049 (3) | 0.007 (3) | 0.019 (3) | 0.007 (2) |
C35 | 0.072 (3) | 0.038 (3) | 0.051 (3) | −0.004 (3) | 0.029 (3) | −0.005 (2) |
C36 | 0.064 (4) | 0.244 (12) | 0.140 (7) | −0.019 (6) | 0.014 (5) | −0.056 (8) |
C37 | 0.102 (6) | 0.122 (6) | 0.072 (5) | −0.016 (5) | 0.016 (5) | 0.009 (4) |
C38 | 0.086 (5) | 0.191 (10) | 0.173 (8) | 0.014 (6) | −0.049 (6) | −0.096 (8) |
C39 | 0.077 (5) | 0.134 (8) | 0.162 (8) | 0.002 (5) | −0.018 (5) | −0.013 (6) |
O17 | 0.066 (2) | 0.072 (3) | 0.141 (4) | −0.009 (2) | 0.013 (3) | 0.027 (3) |
Cl1—C32 | 1.767 (5) | C12—C13 | 1.520 (6) |
Cl2—C32 | 1.766 (4) | C12—C18 | 1.518 (5) |
Cl3—C32 | 1.755 (4) | C13—C14 | 1.523 (6) |
Cl4—C35 | 1.755 (5) | C13—H13 | 0.9800 |
Cl5—C35 | 1.760 (5) | C14—H14A | 0.9700 |
Cl6—C35 | 1.773 (5) | C14—H14B | 0.9700 |
O1—C30 | 1.337 (5) | C15—C17 | 1.544 (6) |
O1—C31 | 1.428 (4) | C15—C16 | 1.544 (6) |
O2—C30 | 1.198 (5) | C16—H16A | 0.9600 |
O3—C30 | 1.327 (5) | C16—H16B | 0.9600 |
O3—C7 | 1.462 (4) | C16—H16C | 0.9600 |
O4—C20 | 1.441 (5) | C17—H17A | 0.9600 |
O4—C5 | 1.452 (5) | C17—H20D | 0.9600 |
O5—C21 | 1.353 (5) | C17—H18D | 0.9600 |
O5—C4 | 1.460 (4) | C18—H18A | 0.9600 |
O6—C21 | 1.198 (5) | C18—H18B | 0.9600 |
O7—C23 | 1.345 (5) | C18—H18C | 0.9600 |
O7—C2 | 1.458 (4) | C19—H19A | 0.9600 |
O8—C23 | 1.212 (5) | C19—H19B | 0.9600 |
O9—C1 | 1.436 (4) | C19—H19C | 0.9600 |
O9—H9 | 0.8200 | C20—H20A | 0.9700 |
O10—C13 | 1.425 (5) | C20—H20B | 0.9700 |
O10—H10 | 0.8200 | C21—C22 | 1.503 (6) |
O11—C33 | 1.332 (5) | C22—H22A | 0.9600 |
O11—C10 | 1.455 (4) | C22—H22B | 0.9600 |
O12—C33 | 1.199 (5) | C22—H22C | 0.9600 |
O13—C33 | 1.341 (5) | C23—C24 | 1.475 (6) |
O13—C34 | 1.443 (5) | C24—C29 | 1.376 (8) |
O14—C9 | 1.207 (4) | C24—C25 | 1.386 (7) |
O15—C37 | 1.202 (7) | C25—C26 | 1.396 (11) |
O16—C37 | 1.295 (7) | C25—H25 | 0.9300 |
O16—C38 | 1.487 (7) | C26—C27 | 1.359 (14) |
C1—C14 | 1.548 (6) | C26—H26 | 0.9300 |
C1—C15 | 1.553 (5) | C27—C28 | 1.363 (13) |
C1—C2 | 1.563 (5) | C27—H27 | 0.9300 |
C2—C3 | 1.570 (5) | C28—C29 | 1.381 (8) |
C2—H2 | 0.9800 | C28—H28 | 0.9300 |
C3—C4 | 1.555 (5) | C29—H29 | 0.9300 |
C3—C8 | 1.582 (5) | C31—C32 | 1.511 (6) |
C3—H3 | 0.9800 | C31—H31A | 0.9700 |
C4—C5 | 1.538 (5) | C31—H31B | 0.9700 |
C4—C20 | 1.534 (5) | C34—C35 | 1.509 (6) |
C5—C6 | 1.507 (5) | C34—H34A | 0.9700 |
C5—H5 | 0.9800 | C34—H34B | 0.9700 |
C6—C7 | 1.517 (5) | C36—C37 | 1.468 (9) |
C6—H6A | 0.9700 | C36—H36A | 0.9600 |
C6—H6B | 0.9700 | C36—H36B | 0.9600 |
C7—C8 | 1.549 (5) | C36—H36C | 0.9600 |
C7—H7 | 0.9800 | C38—C39 | 1.369 (9) |
C8—C19 | 1.526 (5) | C38—H38A | 0.9700 |
C8—C9 | 1.564 (5) | C38—H38B | 0.9700 |
C9—C10 | 1.521 (6) | C39—H39A | 0.9600 |
C10—C11 | 1.498 (5) | C39—H39B | 0.9600 |
C10—H10A | 0.9800 | C39—H39C | 0.9600 |
C11—C12 | 1.341 (5) | O17—H17D | 0.8855 |
C11—C15 | 1.544 (5) | O17—H17E | 0.7953 |
C30—O1—C31 | 113.5 (3) | H20D—C17—H18D | 109.5 |
C30—O3—C7 | 115.0 (3) | C12—C18—H18A | 109.5 |
C20—O4—C5 | 91.6 (3) | C12—C18—H18B | 109.5 |
C21—O5—C4 | 116.4 (3) | H18A—C18—H18B | 109.5 |
C23—O7—C2 | 119.2 (3) | C12—C18—H18C | 109.5 |
C1—O9—H9 | 109.5 | H18A—C18—H18C | 109.5 |
C13—O10—H10 | 109.5 | H18B—C18—H18C | 109.5 |
C33—O11—C10 | 113.3 (3) | C8—C19—H19A | 109.5 |
C33—O13—C34 | 111.9 (4) | C8—C19—H19B | 109.5 |
C37—O16—C38 | 114.0 (6) | H19A—C19—H19B | 109.5 |
O9—C1—C14 | 111.3 (3) | C8—C19—H19C | 109.5 |
O9—C1—C15 | 106.9 (3) | H19A—C19—H19C | 109.5 |
C14—C1—C15 | 110.6 (3) | H19B—C19—H19C | 109.5 |
O9—C1—C2 | 103.6 (3) | O4—C20—C4 | 91.5 (3) |
C14—C1—C2 | 111.4 (3) | O4—C20—H20A | 113.4 |
C15—C1—C2 | 112.8 (3) | C4—C20—H20A | 113.4 |
O7—C2—C1 | 104.1 (3) | O4—C20—H20B | 113.4 |
O7—C2—C3 | 107.6 (3) | C4—C20—H20B | 113.4 |
C1—C2—C3 | 119.1 (3) | H20A—C20—H20B | 110.7 |
O7—C2—H2 | 108.5 | O6—C21—O5 | 123.7 (4) |
C1—C2—H2 | 108.5 | O6—C21—C22 | 124.9 (5) |
C3—C2—H2 | 108.5 | O5—C21—C22 | 111.4 (4) |
C4—C3—C2 | 112.2 (3) | C21—C22—H22A | 109.5 |
C4—C3—C8 | 111.0 (3) | C21—C22—H22B | 109.5 |
C2—C3—C8 | 115.4 (3) | H22A—C22—H22B | 109.5 |
C4—C3—H3 | 105.8 | C21—C22—H22C | 109.5 |
C2—C3—H3 | 105.8 | H22A—C22—H22C | 109.5 |
C8—C3—H3 | 105.8 | H22B—C22—H22C | 109.5 |
O5—C4—C5 | 112.5 (3) | O8—C23—O7 | 123.8 (4) |
O5—C4—C20 | 110.1 (3) | O8—C23—C24 | 124.4 (5) |
C5—C4—C20 | 84.9 (3) | O7—C23—C24 | 111.8 (4) |
O5—C4—C3 | 107.7 (3) | C29—C24—C25 | 119.3 (6) |
C5—C4—C3 | 120.5 (3) | C29—C24—C23 | 122.6 (5) |
C20—C4—C3 | 119.7 (3) | C25—C24—C23 | 118.1 (6) |
O4—C5—C6 | 113.3 (3) | C24—C25—C26 | 119.1 (8) |
O4—C5—C4 | 90.9 (3) | C24—C25—H25 | 120.5 |
C6—C5—C4 | 119.3 (3) | C26—C25—H25 | 120.5 |
O4—C5—H5 | 110.6 | C27—C26—C25 | 121.2 (9) |
C6—C5—H5 | 110.6 | C27—C26—H26 | 119.4 |
C4—C5—H5 | 110.6 | C25—C26—H26 | 119.4 |
C5—C6—C7 | 113.3 (3) | C26—C27—C28 | 119.2 (9) |
C5—C6—H6A | 108.9 | C26—C27—H27 | 120.4 |
C7—C6—H6A | 108.9 | C28—C27—H27 | 120.4 |
C5—C6—H6B | 108.9 | C27—C28—C29 | 121.1 (9) |
C7—C6—H6B | 108.9 | C27—C28—H28 | 119.5 |
H6A—C6—H6B | 107.7 | C29—C28—H28 | 119.5 |
O3—C7—C6 | 107.6 (3) | C24—C29—C28 | 120.1 (7) |
O3—C7—C8 | 108.1 (3) | C24—C29—H29 | 119.9 |
C6—C7—C8 | 114.9 (3) | C28—C29—H29 | 119.9 |
O3—C7—H7 | 108.7 | O2—C30—O3 | 127.3 (4) |
C6—C7—H7 | 108.7 | O2—C30—O1 | 125.4 (4) |
C8—C7—H7 | 108.7 | O3—C30—O1 | 107.2 (4) |
C19—C8—C7 | 111.6 (3) | O1—C31—C32 | 108.3 (3) |
C19—C8—C9 | 107.8 (3) | O1—C31—H31A | 110.0 |
C7—C8—C9 | 104.4 (3) | C32—C31—H31A | 110.0 |
C19—C8—C3 | 112.9 (3) | O1—C31—H31B | 110.0 |
C7—C8—C3 | 103.7 (3) | C32—C31—H31B | 110.0 |
C9—C8—C3 | 116.1 (3) | H31A—C31—H31B | 108.4 |
O14—C9—C10 | 119.6 (4) | C31—C32—Cl3 | 106.9 (3) |
O14—C9—C8 | 119.2 (4) | C31—C32—Cl1 | 110.8 (3) |
C10—C9—C8 | 120.8 (3) | Cl3—C32—Cl1 | 109.9 (2) |
O11—C10—C11 | 110.8 (3) | C31—C32—Cl2 | 109.9 (3) |
O11—C10—C9 | 108.9 (3) | Cl3—C32—Cl2 | 110.1 (2) |
C11—C10—C9 | 114.3 (3) | Cl1—C32—Cl2 | 109.1 (2) |
O11—C10—H10A | 107.5 | O12—C33—O11 | 127.3 (4) |
C11—C10—H10A | 107.5 | O12—C33—O13 | 125.1 (4) |
C9—C10—H10A | 107.5 | O11—C33—O13 | 107.7 (4) |
C12—C11—C10 | 119.9 (4) | O13—C34—C35 | 108.4 (4) |
C12—C11—C15 | 118.8 (4) | O13—C34—H34A | 110.0 |
C10—C11—C15 | 120.7 (3) | C35—C34—H34A | 110.0 |
C11—C12—C13 | 119.4 (4) | O13—C34—H34B | 110.0 |
C11—C12—C18 | 124.8 (4) | C35—C34—H34B | 110.0 |
C13—C12—C18 | 115.7 (3) | H34A—C34—H34B | 108.4 |
O10—C13—C12 | 112.1 (4) | C34—C35—Cl4 | 107.6 (3) |
O10—C13—C14 | 106.4 (3) | C34—C35—Cl5 | 110.8 (3) |
C12—C13—C14 | 112.0 (3) | Cl4—C35—Cl5 | 109.6 (3) |
O10—C13—H13 | 108.8 | C34—C35—Cl6 | 111.1 (3) |
C12—C13—H13 | 108.8 | Cl4—C35—Cl6 | 108.5 (3) |
C14—C13—H13 | 108.8 | Cl5—C35—Cl6 | 109.1 (3) |
C13—C14—C1 | 117.5 (3) | C37—C36—H36A | 109.5 |
C13—C14—H14A | 107.9 | C37—C36—H36B | 109.5 |
C1—C14—H14A | 107.9 | H36A—C36—H36B | 109.5 |
C13—C14—H14B | 107.9 | C37—C36—H36C | 109.5 |
C1—C14—H14B | 107.9 | H36A—C36—H36C | 109.5 |
H14A—C14—H14B | 107.2 | H36B—C36—H36C | 109.5 |
C17—C15—C16 | 104.8 (3) | O15—C37—O16 | 119.8 (7) |
C17—C15—C11 | 115.3 (3) | O15—C37—C36 | 129.7 (8) |
C16—C15—C11 | 110.3 (3) | O16—C37—C36 | 110.6 (6) |
C17—C15—C1 | 110.5 (3) | C39—C38—O16 | 109.7 (6) |
C16—C15—C1 | 110.0 (3) | C39—C38—H38A | 109.7 |
C11—C15—C1 | 106.0 (3) | O16—C38—H38A | 109.7 |
C15—C16—H16A | 109.5 | C39—C38—H38B | 109.7 |
C15—C16—H16B | 109.5 | O16—C38—H38B | 109.7 |
H16A—C16—H16B | 109.5 | H38A—C38—H38B | 108.2 |
C15—C16—H16C | 109.5 | C38—C39—H39A | 109.5 |
H16A—C16—H16C | 109.5 | C38—C39—H39B | 109.5 |
H16B—C16—H16C | 109.5 | H39A—C39—H39B | 109.5 |
C15—C17—H17A | 109.5 | C38—C39—H39C | 109.5 |
C15—C17—H20D | 109.5 | H39A—C39—H39C | 109.5 |
H17A—C17—H20D | 109.5 | H39B—C39—H39C | 109.5 |
C15—C17—H18D | 109.5 | H17D—O17—H17E | 110.4 |
H17A—C17—H18D | 109.5 |
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9···O15 | 0.82 | 2.02 | 2.824 (5) | 166 |
O10—H10···O17 | 0.82 | 2.03 | 2.782 (5) | 151 |
O17—H17D···O1i | 0.89 | 2.38 | 3.260 (5) | 170 |
O17—H17E···O9ii | 0.80 | 2.30 | 3.079 (5) | 165 |
Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) x+1/2, −y+3/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C34H38Cl6O14·C4H8O2·H2O |
Mr | 1001.47 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 296 |
a, b, c (Å) | 14.7029 (12), 16.6256 (14), 18.8428 (15) |
V (Å3) | 4606.0 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.44 |
Crystal size (mm) | 0.45 × 0.42 × 0.40 |
Data collection | |
Diffractometer | Bruker APEXII CCD diffractometer |
Absorption correction | Multi-scan (REQAB; Jacobson, 1998) |
Tmin, Tmax | 0.826, 0.843 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 23553, 8208, 5474 |
Rint | 0.070 |
(sin θ/λ)max (Å−1) | 0.597 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.053, 0.115, 0.98 |
No. of reflections | 8208 |
No. of parameters | 560 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.30, −0.22 |
Absolute structure | Flack (1983), 3609 Friedel pairs |
Absolute structure parameter | −0.04 (6) |
Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), Mercury (Macrae et al., 2006).
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9···O15 | 0.82 | 2.02 | 2.824 (5) | 166.3 |
O10—H10···O17 | 0.82 | 2.03 | 2.782 (5) | 151.3 |
O17—H17D···O1i | 0.89 | 2.38 | 3.260 (5) | 170.3 |
O17—H17E···O9ii | 0.80 | 2.30 | 3.079 (5) | 164.9 |
Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) x+1/2, −y+3/2, −z+1. |