organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

4-Des­­oxy-4β-(4-meth­oxy­carbonyl-1,2,3-triazol-1-yl)podophyllotoxin di­chloro­methane solvate

aSchool of Pharmaceutical Sciences, Tianjin Medical University, Tianjin 300071, People's Republic of China, bRoom of Pharmacognosy, Medical College of Chinese People's Armed Police Forces, Tianjin 300162, People's Republic of China, and cTianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazards, Tianjin 300162, People's Republic of China
*Correspondence e-mail: zuosong203@yahoo.com.cn

(Received 21 October 2009; accepted 24 November 2009; online 28 November 2009)

In the title compound {systematic name: methyl 1-[12-oxo-10-(3,4,5-trimethoxy­phen­yl)-4,6,13-trioxa­tetra­cyclo­[7.7.0.03,7.011,15]hexa­deca-1,3(7),8-trien-16-yl]-1H-1,2,3-triazole-4-carboxyl­ate dichloro­methane solvate}, C26H25N3O9·CH2Cl2, the tetra­hydro­furan ring and the six-membered ring fused to it both display envelope conformations.

Related literature

For similar structures of 4β-N-substituted-4-desoxypodo­phyllotoxin and derivatives, see: Bilal et al. (2008[Bilal, A. & Bhat, P. (2008). Eur. J. Med. Chem. 43, 2067-2072.]); Yu & Chen (2008[Yu, P. F. & Chen, H. (2008). Chem. Pharm. Bull. 56, 831-834.]); Van Maanen et al. (1988[Van Maanen, J. M. S., De Vries, J. & Pinedo, H. M. (1988). J. Natl Cancer Inst. 80, 1526-1533.]). For a review of the structures of azides and triazides, see: Bräse et al. (2005[Bräse, S., Gil, C. & Knepper, K. (2005). Angew. Chem. Int. Ed. 44, 5188-5240.]). For additional background to 1,3-dipolar azide–alkyne cycloaddition reactions, see: Hainsworth et al. (1985[Hainsworth, J. D., Williams, S. D., Einhorn, L. H. & Birch, R. (1985). J. Clin. Oncol. 3, 666-671.]); Huisgen (1963[Huisgen, R. (1963). Angew. Chem. Int. Ed. 2, 565-598.]); Jacobsen et al. (1988[Jacobsen, E. N., Marko, I. & Sharpless, K. B. (1988). J. Am. Chem. Soc. 110, 1968-?.]); Lee (2004[Lee, K. H. (2004). J. Nat. Prod. 273-283]).

[Scheme 1]

Experimental

Crystal data
  • C26H25N3O9·CH2Cl2

  • Mr = 608.42

  • Orthorhombic, P 21 21 21

  • a = 10.377 (2) Å

  • b = 12.639 (3) Å

  • c = 20.463 (4) Å

  • V = 2683.9 (10) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.30 mm−1

  • T = 113 K

  • 0.28 × 0.24 × 0.12 mm

Data collection
  • Rigaku Saturn CCD area-detector diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]) Tmin = 0.920, Tmax = 0.965

  • 22515 measured reflections

  • 6397 independent reflections

  • 5768 reflections with I > 2σ(I)

  • Rint = 0.036

Refinement
  • R[F2 > 2σ(F2)] = 0.036

  • wR(F2) = 0.079

  • S = 1.01

  • 6397 reflections

  • 374 parameters

  • H-atom parameters constrained

  • Δρmax = 0.18 e Å−3

  • Δρmin = −0.34 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 2800 Friedel pairs

  • Flack parameter: 0.04 (4)

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Podophyllotoxin derivatives such as Etoposide and Teniposide are in clinical use as antineoplastic agents. NK611, as well as NPF, GL-311 and TOP53 are presently under clinical trials. These podophyllotoxin ligands block the catalytic activity of DNA-topoisomerase II by stabilizing a cleavable enzyme DNA complex in which the DNA is cleaved and covalently linked to the enzyme (Hainsworth,1985). Its high toxicity has limited its application as a drug in cancer chemotherapy. Hence, extensive structure modifications have been performed since the 1950's. Meanwhile, click chemistry with copper-catalyzed Huisgen 1,3-dipolar azide-alkyne cycloaddition (CuAAC) producing 1,2,3-triazoles has exhibited increasing importance in organic chemistry due to the chemoselective nature and mild reaction conditions (Bräse, 2005). Moreover, as a functional group the 1,2,3-triazole ring has found widespread occurrence in a variety of fields. These advantages have stimulated us to couple the podophyllotoxin parent nucleus with 1,2,3-triazole to give potential anticancer candidates. Herein we report the crystal structure of the title compound (Fig.1), which can be used as a candidate for anti-tumor molecules. The asymmetric unit consists of the organic molecule and one dichloromethane molecule, C26H25N3O9.CH2Cl2. The configuration of this derivative is the same as found for podophyllotoxin, which is compatible with the mild reaction conditions. The compound contains three planar moieties: plane A consisting of atoms C10 to C22, plane B consisting of atoms C1 to C6, and the triazole ring as plane C. The dihedral angles between the planes A/B, B/C and A/C are 83.82 (6)°, 32.06 (8)° and 86.54 (7)°, respectively.

Related literature top

For similar structures of 4β-N-substituted-4-desoxypodophyllotoxin and derivatives, see: Bilal et al. (2008); Yu et al. (2008); Van Maanen et al. (1988). For a review of the structures of azides and triazides, see: Bräse et al. (2005). For additional background, see: Hainsworth et al. (1985); Huisgen (1963); Jacobsen et al. (1988); Lee et al. (2004).

Experimental top

The title compound was synthesized from natural product podophyllotoxin by copper-catalyzed Huisgen 1, 3-dipolar azide-alkyne cycloaddition. Crystals of the title compound suitable for crystal structure analysis were obtained from a dichloromethane solution by slowly evaporating the solvent.

Refinement top

All H atoms were located in difference Fourier maps and refined independently with isotropic displacement parameters.

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (Rigaku/MSC, 2005); 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: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms.
methyl 1-[12-oxo-10-(3,4,5-trimethoxyphenyl)-4,6,13- trioxatetracyclo[7.7.0.03,7.011,15]hexadeca-1,3(7),8-trien-16-yl]- 1H-1,2,3-triazole-4-carboxylate dichloromethane solvate top
Crystal data top
C26H25N3O9·CH2Cl2Dx = 1.506 Mg m3
Mr = 608.42Melting point = 212–213 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 9219 reflections
a = 10.377 (2) Åθ = 1.9–27.9°
b = 12.639 (3) ŵ = 0.30 mm1
c = 20.463 (4) ÅT = 113 K
V = 2683.9 (10) Å3Block, colorless
Z = 40.28 × 0.24 × 0.12 mm
F(000) = 1264
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
6397 independent reflections
Radiation source: rotating anode5768 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.036
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 1.9°
ω and ϕ scansh = 1313
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
k = 1216
Tmin = 0.920, Tmax = 0.965l = 2626
22515 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.079 w = 1/[σ2(Fo2) + (0.0476P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max = 0.001
6397 reflectionsΔρmax = 0.18 e Å3
374 parametersΔρmin = 0.34 e Å3
0 restraintsAbsolute structure: Flack (1983), 2800 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.04 (4)
Crystal data top
C26H25N3O9·CH2Cl2V = 2683.9 (10) Å3
Mr = 608.42Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 10.377 (2) ŵ = 0.30 mm1
b = 12.639 (3) ÅT = 113 K
c = 20.463 (4) Å0.28 × 0.24 × 0.12 mm
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
6397 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
5768 reflections with I > 2σ(I)
Tmin = 0.920, Tmax = 0.965Rint = 0.036
22515 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.079Δρmax = 0.18 e Å3
S = 1.01Δρmin = 0.34 e Å3
6397 reflectionsAbsolute structure: Flack (1983), 2800 Friedel pairs
374 parametersAbsolute structure parameter: 0.04 (4)
0 restraints
Special details top

Experimental. Both Cu+ and Cu2+ can be used as catalyst while combined with respective additives.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.81730 (11)0.46481 (8)0.07929 (6)0.0222 (2)
O21.02230 (11)0.38471 (8)0.13992 (5)0.0200 (2)
O31.07335 (11)0.17818 (9)0.13872 (6)0.0242 (3)
O41.03010 (12)0.07454 (9)0.18541 (6)0.0279 (3)
O51.04059 (12)0.10864 (9)0.17747 (6)0.0263 (3)
O60.49041 (12)0.00212 (9)0.11823 (6)0.0273 (3)
O70.50203 (13)0.17197 (9)0.09864 (6)0.0313 (3)
O80.35597 (12)0.14406 (9)0.20717 (6)0.0254 (3)
O90.30253 (11)0.31101 (8)0.17946 (6)0.0242 (3)
N10.60318 (12)0.17930 (9)0.04644 (6)0.0167 (3)
N20.56517 (13)0.28046 (10)0.03289 (7)0.0234 (3)
N30.47699 (14)0.30643 (10)0.07549 (6)0.0226 (3)
C10.78479 (14)0.18283 (11)0.03338 (7)0.0162 (3)
C20.75602 (15)0.29059 (11)0.03655 (7)0.0176 (3)
H20.68350.31800.01380.021*
C30.83415 (15)0.35759 (11)0.07318 (8)0.0172 (3)
C40.93996 (15)0.31698 (12)0.10722 (7)0.0165 (3)
C50.96690 (15)0.20875 (12)0.10457 (7)0.0175 (3)
C60.88965 (15)0.14181 (12)0.06738 (8)0.0178 (3)
H60.90850.06830.06520.021*
C70.72731 (16)0.51437 (13)0.03645 (8)0.0261 (4)
H7A0.75490.50420.00890.039*
H7B0.64190.48280.04270.039*
H7C0.72320.59020.04620.039*
C80.98547 (17)0.40051 (14)0.20675 (8)0.0245 (4)
H8A0.90160.43610.20840.037*
H8B0.97940.33190.22880.037*
H8C1.05020.44430.22870.037*
C91.09771 (18)0.06681 (13)0.14314 (9)0.0279 (4)
H9A1.02240.03140.16200.042*
H9B1.11450.03840.09940.042*
H9C1.17290.05450.17110.042*
C100.70229 (15)0.11348 (11)0.01110 (7)0.0165 (3)
H100.65400.16230.04070.020*
C110.78712 (15)0.04464 (11)0.05453 (7)0.0161 (3)
C120.86601 (15)0.09890 (12)0.09961 (8)0.0192 (3)
H120.86370.17380.10290.023*
C130.94594 (15)0.03996 (12)0.13838 (8)0.0188 (3)
C141.09057 (17)0.01795 (14)0.21149 (9)0.0278 (4)
H14A1.07210.02390.25880.033*
H14B1.18510.01350.20560.033*
C150.95192 (15)0.06919 (12)0.13392 (8)0.0188 (3)
C160.87764 (15)0.12393 (12)0.09064 (8)0.0181 (3)
H160.88280.19880.08750.022*
C170.79280 (14)0.06537 (11)0.05070 (7)0.0156 (3)
C180.70594 (15)0.13007 (11)0.00655 (7)0.0162 (3)
H180.75870.18800.01330.019*
C190.65391 (15)0.06140 (11)0.04854 (8)0.0174 (3)
H190.72650.04570.07920.021*
C200.53937 (17)0.09906 (12)0.08870 (8)0.0224 (3)
H20A0.56670.15030.12260.027*
H20B0.47340.13250.06050.027*
C210.52869 (16)0.08367 (13)0.08212 (8)0.0224 (3)
C220.60149 (15)0.04366 (11)0.02292 (7)0.0173 (3)
H220.53530.02580.01080.021*
C230.53786 (16)0.14106 (12)0.09778 (7)0.0172 (3)
H230.54560.07310.11720.021*
C240.45700 (15)0.22220 (12)0.11611 (8)0.0169 (3)
C250.36761 (15)0.22017 (12)0.17193 (8)0.0192 (3)
C260.21945 (17)0.31309 (14)0.23663 (8)0.0287 (4)
H26A0.15000.26130.23120.043*
H26B0.27000.29540.27560.043*
H26C0.18240.38390.24160.043*
Cl10.26269 (6)0.39288 (4)0.23482 (3)0.05616 (18)
Cl20.21387 (5)0.18814 (4)0.29584 (2)0.03992 (13)
C270.1834 (2)0.27027 (14)0.22719 (10)0.0343 (4)
H27A0.21340.23420.18700.041*
H27B0.08950.28230.22310.041*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0274 (6)0.0121 (5)0.0272 (6)0.0025 (4)0.0052 (5)0.0009 (4)
O20.0216 (6)0.0202 (6)0.0181 (5)0.0065 (4)0.0010 (5)0.0023 (4)
O30.0228 (6)0.0206 (6)0.0293 (6)0.0030 (5)0.0106 (5)0.0002 (5)
O40.0315 (7)0.0217 (6)0.0305 (7)0.0010 (5)0.0133 (6)0.0014 (5)
O50.0284 (6)0.0208 (6)0.0297 (7)0.0024 (5)0.0120 (5)0.0002 (5)
O60.0307 (7)0.0246 (6)0.0267 (6)0.0017 (5)0.0094 (5)0.0035 (5)
O70.0314 (7)0.0243 (6)0.0381 (7)0.0046 (5)0.0067 (6)0.0088 (6)
O80.0291 (7)0.0228 (6)0.0241 (6)0.0017 (5)0.0064 (5)0.0022 (5)
O90.0249 (6)0.0238 (6)0.0239 (6)0.0066 (5)0.0036 (5)0.0035 (5)
N10.0195 (6)0.0119 (6)0.0186 (6)0.0005 (5)0.0004 (5)0.0004 (5)
N20.0275 (8)0.0157 (7)0.0269 (8)0.0054 (5)0.0019 (6)0.0033 (6)
N30.0256 (8)0.0194 (7)0.0227 (7)0.0059 (6)0.0025 (6)0.0006 (6)
C10.0182 (7)0.0155 (7)0.0149 (7)0.0014 (6)0.0009 (6)0.0006 (6)
C20.0177 (8)0.0168 (8)0.0184 (8)0.0011 (6)0.0010 (6)0.0016 (6)
C30.0212 (8)0.0121 (7)0.0181 (8)0.0000 (6)0.0037 (6)0.0006 (6)
C40.0175 (8)0.0178 (7)0.0141 (7)0.0045 (6)0.0001 (6)0.0016 (6)
C50.0162 (8)0.0215 (8)0.0148 (7)0.0009 (6)0.0015 (6)0.0031 (6)
C60.0195 (8)0.0156 (7)0.0184 (8)0.0008 (6)0.0006 (6)0.0002 (6)
C70.0264 (9)0.0177 (8)0.0342 (10)0.0026 (6)0.0033 (8)0.0017 (7)
C80.0290 (9)0.0268 (9)0.0178 (8)0.0008 (7)0.0028 (7)0.0030 (7)
C90.0315 (9)0.0257 (9)0.0267 (9)0.0104 (7)0.0078 (8)0.0010 (7)
C100.0185 (8)0.0138 (7)0.0171 (8)0.0009 (6)0.0027 (6)0.0005 (6)
C110.0169 (8)0.0155 (7)0.0158 (7)0.0005 (6)0.0042 (6)0.0007 (5)
C120.0212 (8)0.0157 (8)0.0206 (8)0.0015 (6)0.0031 (6)0.0012 (6)
C130.0185 (8)0.0188 (8)0.0192 (8)0.0038 (6)0.0015 (6)0.0020 (6)
C140.0287 (9)0.0268 (9)0.0278 (9)0.0036 (7)0.0089 (7)0.0029 (7)
C150.0176 (8)0.0191 (8)0.0196 (8)0.0028 (6)0.0007 (6)0.0017 (6)
C160.0192 (8)0.0152 (8)0.0199 (8)0.0012 (6)0.0024 (6)0.0004 (6)
C170.0155 (7)0.0151 (7)0.0162 (7)0.0005 (5)0.0035 (6)0.0003 (5)
C180.0171 (8)0.0153 (7)0.0162 (7)0.0009 (6)0.0036 (6)0.0010 (6)
C190.0195 (8)0.0160 (8)0.0169 (8)0.0006 (6)0.0023 (6)0.0010 (6)
C200.0262 (9)0.0195 (8)0.0214 (8)0.0008 (7)0.0025 (7)0.0023 (6)
C210.0186 (8)0.0255 (9)0.0231 (8)0.0017 (6)0.0006 (7)0.0041 (7)
C220.0172 (7)0.0152 (8)0.0194 (8)0.0004 (6)0.0037 (6)0.0026 (6)
C230.0204 (8)0.0164 (7)0.0148 (8)0.0011 (6)0.0003 (6)0.0007 (6)
C240.0184 (8)0.0156 (7)0.0166 (8)0.0006 (6)0.0026 (6)0.0014 (6)
C250.0169 (8)0.0215 (8)0.0192 (8)0.0009 (6)0.0013 (7)0.0053 (6)
C260.0261 (9)0.0301 (9)0.0300 (9)0.0017 (8)0.0072 (8)0.0105 (8)
Cl10.0722 (4)0.0437 (3)0.0526 (3)0.0320 (3)0.0287 (3)0.0187 (3)
Cl20.0490 (3)0.0366 (3)0.0342 (3)0.0004 (2)0.0064 (2)0.0110 (2)
C270.0350 (11)0.0262 (9)0.0417 (11)0.0044 (8)0.0050 (9)0.0084 (8)
Geometric parameters (Å, º) top
O1—C31.3722 (18)C9—H9A0.9800
O1—C71.4258 (19)C9—H9B0.9800
O2—C41.3823 (17)C9—H9C0.9800
O2—C81.4339 (19)C10—C111.524 (2)
O3—C51.3631 (19)C10—C221.535 (2)
O3—C91.433 (2)C10—H101.0000
O4—C131.3710 (19)C11—C171.394 (2)
O4—C141.430 (2)C11—C121.411 (2)
O5—C151.3747 (19)C12—C131.368 (2)
O5—C141.438 (2)C12—H120.9500
O6—C211.371 (2)C13—C151.384 (2)
O6—C201.4575 (19)C14—H14A0.9900
O7—C211.1985 (19)C14—H14B0.9900
O8—C251.2084 (19)C15—C161.363 (2)
O9—C251.3409 (19)C16—C171.411 (2)
O9—C261.454 (2)C16—H160.9500
N1—C231.340 (2)C17—C181.516 (2)
N1—N21.3664 (18)C18—C191.522 (2)
N1—C181.4800 (19)C18—H181.0000
N2—N31.3057 (19)C19—C201.521 (2)
N3—C241.367 (2)C19—C221.528 (2)
C1—C61.392 (2)C19—H191.0000
C1—C21.396 (2)C20—H20A0.9900
C1—C101.526 (2)C20—H20B0.9900
C2—C31.392 (2)C21—C221.515 (2)
C2—H20.9500C22—H221.0000
C3—C41.398 (2)C23—C241.377 (2)
C4—C51.397 (2)C23—H230.9500
C5—C61.392 (2)C24—C251.472 (2)
C6—H60.9500C26—H26A0.9800
C7—H7A0.9800C26—H26B0.9800
C7—H7B0.9800C26—H26C0.9800
C7—H7C0.9800Cl1—C271.7613 (19)
C8—H8A0.9800Cl2—C271.775 (2)
C8—H8B0.9800C27—H27A0.9900
C8—H8C0.9800C27—H27B0.9900
C3—O1—C7117.47 (12)O4—C14—O5108.23 (13)
C4—O2—C8112.53 (12)O4—C14—H14A110.1
C5—O3—C9116.98 (12)O5—C14—H14A110.1
C13—O4—C14106.31 (12)O4—C14—H14B110.1
C15—O5—C14105.43 (12)O5—C14—H14B110.1
C21—O6—C20109.90 (12)H14A—C14—H14B108.4
C25—O9—C26114.00 (12)C16—C15—O5128.01 (14)
C23—N1—N2110.51 (12)C16—C15—C13121.57 (15)
C23—N1—C18130.16 (12)O5—C15—C13110.42 (14)
N2—N1—C18119.31 (12)C15—C16—C17117.59 (14)
N3—N2—N1107.58 (12)C15—C16—H16121.2
N2—N3—C24108.46 (12)C17—C16—H16121.2
C6—C1—C2120.50 (14)C11—C17—C16121.13 (14)
C6—C1—C10121.51 (13)C11—C17—C18123.14 (14)
C2—C1—C10117.91 (13)C16—C17—C18115.68 (13)
C3—C2—C1119.62 (14)N1—C18—C17109.06 (12)
C3—C2—H2120.2N1—C18—C19113.12 (13)
C1—C2—H2120.2C17—C18—C19110.17 (12)
O1—C3—C2125.16 (14)N1—C18—H18108.1
O1—C3—C4114.67 (14)C17—C18—H18108.1
C2—C3—C4120.17 (14)C19—C18—H18108.1
O2—C4—C5120.10 (14)C20—C19—C18119.93 (12)
O2—C4—C3119.95 (13)C20—C19—C22100.32 (12)
C5—C4—C3119.81 (13)C18—C19—C22111.58 (13)
O3—C5—C6125.09 (14)C20—C19—H19108.1
O3—C5—C4114.81 (13)C18—C19—H19108.1
C6—C5—C4120.07 (14)C22—C19—H19108.1
C1—C6—C5119.82 (14)O6—C20—C19103.49 (12)
C1—C6—H6120.1O6—C20—H20A111.1
C5—C6—H6120.1C19—C20—H20A111.1
O1—C7—H7A109.5O6—C20—H20B111.1
O1—C7—H7B109.5C19—C20—H20B111.1
H7A—C7—H7B109.5H20A—C20—H20B109.0
O1—C7—H7C109.5O7—C21—O6121.17 (15)
H7A—C7—H7C109.5O7—C21—C22130.67 (15)
H7B—C7—H7C109.5O6—C21—C22108.15 (13)
O2—C8—H8A109.5C21—C22—C19101.14 (13)
O2—C8—H8B109.5C21—C22—C10120.70 (12)
H8A—C8—H8B109.5C19—C22—C10114.36 (13)
O2—C8—H8C109.5C21—C22—H22106.6
H8A—C8—H8C109.5C19—C22—H22106.6
H8B—C8—H8C109.5C10—C22—H22106.6
O3—C9—H9A109.5N1—C23—C24104.66 (13)
O3—C9—H9B109.5N1—C23—H23127.7
H9A—C9—H9B109.5C24—C23—H23127.7
O3—C9—H9C109.5N3—C24—C23108.78 (14)
H9A—C9—H9C109.5N3—C24—C25125.55 (14)
H9B—C9—H9C109.5C23—C24—C25125.63 (14)
C11—C10—C1110.59 (12)O8—C25—O9124.24 (15)
C11—C10—C22109.26 (12)O8—C25—C24122.69 (14)
C1—C10—C22116.22 (12)O9—C25—C24113.07 (14)
C11—C10—H10106.8O9—C26—H26A109.5
C1—C10—H10106.8O9—C26—H26B109.5
C22—C10—H10106.8H26A—C26—H26B109.5
C17—C11—C12119.80 (14)O9—C26—H26C109.5
C17—C11—C10124.14 (14)H26A—C26—H26C109.5
C12—C11—C10116.03 (12)H26B—C26—H26C109.5
C13—C12—C11117.78 (14)Cl1—C27—Cl2111.18 (11)
C13—C12—H12121.1Cl1—C27—H27A109.4
C11—C12—H12121.1Cl2—C27—H27A109.4
C12—C13—O4128.28 (14)Cl1—C27—H27B109.4
C12—C13—C15122.11 (15)Cl2—C27—H27B109.4
O4—C13—C15109.60 (14)H27A—C27—H27B108.0
C23—N1—N2—N30.34 (17)C13—C15—C16—C170.7 (2)
C18—N1—N2—N3178.32 (12)C12—C11—C17—C160.9 (2)
N1—N2—N3—C240.55 (17)C10—C11—C17—C16177.31 (13)
C6—C1—C2—C31.0 (2)C12—C11—C17—C18176.30 (13)
C10—C1—C2—C3175.82 (14)C10—C11—C17—C185.5 (2)
C7—O1—C3—C211.4 (2)C15—C16—C17—C111.2 (2)
C7—O1—C3—C4168.31 (14)C15—C16—C17—C18176.13 (14)
C1—C2—C3—O1178.91 (14)C23—N1—C18—C1737.7 (2)
C1—C2—C3—C40.7 (2)N2—N1—C18—C17140.67 (13)
C8—O2—C4—C592.48 (17)C23—N1—C18—C1985.29 (18)
C8—O2—C4—C391.68 (17)N2—N1—C18—C1996.36 (15)
O1—C3—C4—O24.1 (2)C11—C17—C18—N1103.10 (16)
C2—C3—C4—O2175.64 (14)C16—C17—C18—N174.20 (16)
O1—C3—C4—C5179.91 (13)C11—C17—C18—C1921.6 (2)
C2—C3—C4—C50.2 (2)C16—C17—C18—C19161.08 (13)
C9—O3—C5—C68.2 (2)N1—C18—C19—C2041.98 (18)
C9—O3—C5—C4173.77 (14)C17—C18—C19—C20164.34 (13)
O2—C4—C5—O33.2 (2)N1—C18—C19—C2274.75 (15)
C3—C4—C5—O3179.03 (14)C17—C18—C19—C2247.60 (17)
O2—C4—C5—C6174.94 (14)C21—O6—C20—C1922.57 (16)
C3—C4—C5—C60.9 (2)C18—C19—C20—O6160.39 (13)
C2—C1—C6—C50.3 (2)C22—C19—C20—O637.97 (14)
C10—C1—C6—C5176.39 (14)C20—O6—C21—O7177.91 (16)
O3—C5—C6—C1178.54 (14)C20—O6—C21—C223.11 (17)
C4—C5—C6—C10.6 (2)O7—C21—C22—C19153.98 (19)
C6—C1—C10—C1145.76 (19)O6—C21—C22—C1927.17 (16)
C2—C1—C10—C11131.05 (14)O7—C21—C22—C1026.7 (3)
C6—C1—C10—C2279.53 (18)O6—C21—C22—C10154.47 (14)
C2—C1—C10—C22103.66 (16)C20—C19—C22—C2138.84 (14)
C1—C10—C11—C17114.25 (16)C18—C19—C22—C21166.96 (12)
C22—C10—C11—C1714.9 (2)C20—C19—C22—C10170.17 (13)
C1—C10—C11—C1263.98 (17)C18—C19—C22—C1061.71 (17)
C22—C10—C11—C12166.88 (13)C11—C10—C22—C21163.16 (13)
C17—C11—C12—C130.1 (2)C1—C10—C22—C2137.2 (2)
C10—C11—C12—C13178.42 (14)C11—C10—C22—C1942.11 (17)
C11—C12—C13—O4179.74 (15)C1—C10—C22—C1983.85 (16)
C11—C12—C13—C150.7 (2)N2—N1—C23—C240.01 (17)
C14—O4—C13—C12179.90 (17)C18—N1—C23—C24178.48 (15)
C14—O4—C13—C150.29 (18)N2—N3—C24—C230.56 (18)
C13—O4—C14—O50.88 (18)N2—N3—C24—C25178.25 (14)
C15—O5—C14—O41.12 (18)N1—C23—C24—N30.34 (17)
C14—O5—C15—C16179.58 (17)N1—C23—C24—C25178.03 (14)
C14—O5—C15—C130.96 (18)C26—O9—C25—O83.0 (2)
C12—C13—C15—C160.3 (3)C26—O9—C25—C24176.46 (13)
O4—C13—C15—C16179.94 (14)N3—C24—C25—O8178.28 (16)
C12—C13—C15—O5179.20 (14)C23—C24—C25—O81.0 (3)
O4—C13—C15—O50.43 (19)N3—C24—C25—O91.2 (2)
O5—C15—C16—C17179.92 (15)C23—C24—C25—O9178.50 (15)

Experimental details

Crystal data
Chemical formulaC26H25N3O9·CH2Cl2
Mr608.42
Crystal system, space groupOrthorhombic, P212121
Temperature (K)113
a, b, c (Å)10.377 (2), 12.639 (3), 20.463 (4)
V3)2683.9 (10)
Z4
Radiation typeMo Kα
µ (mm1)0.30
Crystal size (mm)0.28 × 0.24 × 0.12
Data collection
DiffractometerRigaku Saturn CCD area-detector
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku/MSC, 2005)
Tmin, Tmax0.920, 0.965
No. of measured, independent and
observed [I > 2σ(I)] reflections
22515, 6397, 5768
Rint0.036
(sin θ/λ)max1)0.658
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.079, 1.01
No. of reflections6397
No. of parameters374
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.18, 0.34
Absolute structureFlack (1983), 2800 Friedel pairs
Absolute structure parameter0.04 (4)

Computer programs: CrystalClear (Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 30873363), the Great Program of the Science Foundation of Tianjin (09ZCKFNC01200) and the Program of the Science Foundation of Tianjin (08JCYBJC070000).

References

First citationBilal, A. & Bhat, P. (2008). Eur. J. Med. Chem. 43, 2067–2072.  Web of Science PubMed Google Scholar
First citationBräse, S., Gil, C. & Knepper, K. (2005). Angew. Chem. Int. Ed. 44, 5188–5240.  Google Scholar
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationHainsworth, J. D., Williams, S. D., Einhorn, L. H. & Birch, R. (1985). J. Clin. Oncol. 3, 666–671.  CAS PubMed Web of Science Google Scholar
First citationHuisgen, R. (1963). Angew. Chem. Int. Ed. 2, 565–598.  CrossRef Google Scholar
First citationJacobsen, E. N., Marko, I. & Sharpless, K. B. (1988). J. Am. Chem. Soc. 110, 1968–?.  Google Scholar
First citationLee, K. H. (2004). J. Nat. Prod. 273–283  Google Scholar
First citationRigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationVan Maanen, J. M. S., De Vries, J. & Pinedo, H. M. (1988). J. Natl Cancer Inst. 80, 1526–1533.  CrossRef CAS PubMed Web of Science Google Scholar
First citationYu, P. F. & Chen, H. (2008). Chem. Pharm. Bull. 56, 831–834.  Web of Science CrossRef PubMed CAS Google Scholar

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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds