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

Zuo, S.; Chen, H.; Lu, Y.; Cao, B.; Liu, D.

doi:10.1107/S1600536809050612

organic compounds

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ISSN: 2056-9890

Volume 65| Part 12| December 2009| Page o3257

doi:10.1107/S1600536809050612

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

Song Zuo,^a Hong Chen,^b ^* Yanling Lu,^a Bo Cao ^c and Dailin Liu ^b

^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[7.7.0.0^3,7.0^11,15]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 ); Yu & Chen (2008 ); Van Maanen et al. (1988 ). For a review of the structures of azides and triazides, see: Bräse et al. (2005 ). For additional background to 1,3-dipolar azide–alkyne cycloaddition reactions, see: Hainsworth et al. (1985 ); Huisgen (1963 ); Jacobsen et al. (1988 ); Lee (2004 ).

Experimental

Crystal data

C₂₆H₂₅N₃O₉·CH₂Cl₂
M_r = 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 ) T_min = 0.920, T_max = 0.965
22515 measured reflections
6397 independent reflections
5768 reflections with I > 2σ(I)
R_int = 0.036

Refinement

R[F² > 2σ(F²)] = 0.036
wR(F²) = 0.079
S = 1.01
6397 reflections
374 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.34 e Å⁻³
Absolute structure: Flack (1983 ), 2800 Friedel pairs
Flack parameter: 0.04 (4)

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

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809050612/vm2011sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809050612/vm2011Isup2.hkl

checkCIF report

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.

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

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[7.7.0.0^3,7.0^11,15]hexadeca-1,3(7),8-trien-16-yl]- 1H-1,2,3-triazole-4-carboxylate dichloromethane solvate top

Crystal data top

C₂₆H₂₅N₃O₉·CH₂Cl₂	D_x = 1.506 Mg m⁻³
M_r = 608.42	Melting point = 212–213 K
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9219 reflections
a = 10.377 (2) Å	θ = 1.9–27.9°
b = 12.639 (3) Å	µ = 0.30 mm⁻¹
c = 20.463 (4) Å	T = 113 K
V = 2683.9 (10) Å³	Block, colorless
Z = 4	0.28 × 0.24 × 0.12 mm
F(000) = 1264

Data collection top

Rigaku Saturn CCD area-detector diffractometer	6397 independent reflections
Radiation source: rotating anode	5768 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.036
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 1.9°
ω and ϕ scans	h = −13→13
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −12→16
T_min = 0.920, T_max = 0.965	l = −26→26
22515 measured reflections

Refinement top

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)] = 0.036	H-atom parameters constrained
wR(F²) = 0.079	w = 1/[σ²(F_o²) + (0.0476P)²] where P = (F_o² + 2F_c²)/3
S = 1.01	(Δ/σ)_max = 0.001
6397 reflections	Δρ_max = 0.18 e Å⁻³
374 parameters	Δρ_min = −0.34 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 2800 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.04 (4)

Crystal data top

C₂₆H₂₅N₃O₉·CH₂Cl₂	V = 2683.9 (10) Å³
M_r = 608.42	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 10.377 (2) Å	µ = 0.30 mm⁻¹
b = 12.639 (3) Å	T = 113 K
c = 20.463 (4) Å	0.28 × 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)
T_min = 0.920, T_max = 0.965	R_int = 0.036
22515 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.036	H-atom parameters constrained
wR(F²) = 0.079	Δρ_max = 0.18 e Å⁻³
S = 1.01	Δρ_min = −0.34 e Å⁻³
6397 reflections	Absolute structure: Flack (1983), 2800 Friedel pairs
374 parameters	Absolute 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

	x	y	z	U_iso*/U_eq
O1	0.81730 (11)	0.46481 (8)	−0.07929 (6)	0.0222 (2)
O2	1.02230 (11)	0.38471 (8)	−0.13992 (5)	0.0200 (2)
O3	1.07335 (11)	0.17818 (9)	−0.13872 (6)	0.0242 (3)
O4	1.03010 (12)	0.07454 (9)	0.18541 (6)	0.0279 (3)
O5	1.04059 (12)	−0.10864 (9)	0.17747 (6)	0.0263 (3)
O6	0.49041 (12)	−0.00212 (9)	−0.11823 (6)	0.0273 (3)
O7	0.50203 (13)	0.17197 (9)	−0.09864 (6)	0.0313 (3)
O8	0.35597 (12)	−0.14406 (9)	0.20717 (6)	0.0254 (3)
O9	0.30253 (11)	−0.31101 (8)	0.17946 (6)	0.0242 (3)
N1	0.60318 (12)	−0.17930 (9)	0.04644 (6)	0.0167 (3)
N2	0.56517 (13)	−0.28046 (10)	0.03289 (7)	0.0234 (3)
N3	0.47699 (14)	−0.30643 (10)	0.07549 (6)	0.0226 (3)
C1	0.78479 (14)	0.18283 (11)	−0.03338 (7)	0.0162 (3)
C2	0.75602 (15)	0.29059 (11)	−0.03655 (7)	0.0176 (3)
H2	0.6835	0.3180	−0.0138	0.021*
C3	0.83415 (15)	0.35759 (11)	−0.07318 (8)	0.0172 (3)
C4	0.93996 (15)	0.31698 (12)	−0.10722 (7)	0.0165 (3)
C5	0.96690 (15)	0.20875 (12)	−0.10457 (7)	0.0175 (3)
C6	0.88965 (15)	0.14181 (12)	−0.06738 (8)	0.0178 (3)
H6	0.9085	0.0683	−0.0652	0.021*
C7	0.72731 (16)	0.51437 (13)	−0.03645 (8)	0.0261 (4)
H7A	0.7549	0.5042	0.0089	0.039*
H7B	0.6419	0.4828	−0.0427	0.039*
H7C	0.7232	0.5902	−0.0462	0.039*
C8	0.98547 (17)	0.40051 (14)	−0.20675 (8)	0.0245 (4)
H8A	0.9016	0.4361	−0.2084	0.037*
H8B	0.9794	0.3319	−0.2288	0.037*
H8C	1.0502	0.4443	−0.2287	0.037*
C9	1.09771 (18)	0.06681 (13)	−0.14314 (9)	0.0279 (4)
H9A	1.0224	0.0314	−0.1620	0.042*
H9B	1.1145	0.0384	−0.0994	0.042*
H9C	1.1729	0.0545	−0.1711	0.042*
C10	0.70229 (15)	0.11348 (11)	0.01110 (7)	0.0165 (3)
H10	0.6540	0.1623	0.0407	0.020*
C11	0.78712 (15)	0.04464 (11)	0.05453 (7)	0.0161 (3)
C12	0.86601 (15)	0.09890 (12)	0.09961 (8)	0.0192 (3)
H12	0.8637	0.1738	0.1029	0.023*
C13	0.94594 (15)	0.03996 (12)	0.13838 (8)	0.0188 (3)
C14	1.09057 (17)	−0.01795 (14)	0.21149 (9)	0.0278 (4)
H14A	1.0721	−0.0239	0.2588	0.033*
H14B	1.1851	−0.0135	0.2056	0.033*
C15	0.95192 (15)	−0.06919 (12)	0.13392 (8)	0.0188 (3)
C16	0.87764 (15)	−0.12393 (12)	0.09064 (8)	0.0181 (3)
H16	0.8828	−0.1988	0.0875	0.022*
C17	0.79280 (14)	−0.06537 (11)	0.05070 (7)	0.0156 (3)
C18	0.70594 (15)	−0.13007 (11)	0.00655 (7)	0.0162 (3)
H18	0.7587	−0.1880	−0.0133	0.019*
C19	0.65391 (15)	−0.06140 (11)	−0.04854 (8)	0.0174 (3)
H19	0.7265	−0.0457	−0.0792	0.021*
C20	0.53937 (17)	−0.09906 (12)	−0.08870 (8)	0.0224 (3)
H20A	0.5667	−0.1503	−0.1226	0.027*
H20B	0.4734	−0.1325	−0.0605	0.027*
C21	0.52869 (16)	0.08367 (13)	−0.08212 (8)	0.0224 (3)
C22	0.60149 (15)	0.04366 (11)	−0.02292 (7)	0.0173 (3)
H22	0.5353	0.0258	0.0108	0.021*
C23	0.53786 (16)	−0.14106 (12)	0.09778 (7)	0.0172 (3)
H23	0.5456	−0.0731	0.1172	0.021*
C24	0.45700 (15)	−0.22220 (12)	0.11611 (8)	0.0169 (3)
C25	0.36761 (15)	−0.22017 (12)	0.17193 (8)	0.0192 (3)
C26	0.21945 (17)	−0.31309 (14)	0.23663 (8)	0.0287 (4)
H26A	0.1500	−0.2613	0.2312	0.043*
H26B	0.2700	−0.2954	0.2756	0.043*
H26C	0.1824	−0.3839	0.2416	0.043*
Cl1	0.26269 (6)	0.39288 (4)	0.23482 (3)	0.05616 (18)
Cl2	0.21387 (5)	0.18814 (4)	0.29584 (2)	0.03992 (13)
C27	0.1834 (2)	0.27027 (14)	0.22719 (10)	0.0343 (4)
H27A	0.2134	0.2342	0.1870	0.041*
H27B	0.0895	0.2823	0.2231	0.041*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0274 (6)	0.0121 (5)	0.0272 (6)	0.0025 (4)	0.0052 (5)	0.0009 (4)
O2	0.0216 (6)	0.0202 (6)	0.0181 (5)	−0.0065 (4)	0.0010 (5)	0.0023 (4)
O3	0.0228 (6)	0.0206 (6)	0.0293 (6)	0.0030 (5)	0.0106 (5)	−0.0002 (5)
O4	0.0315 (7)	0.0217 (6)	0.0305 (7)	−0.0010 (5)	−0.0133 (6)	−0.0014 (5)
O5	0.0284 (6)	0.0208 (6)	0.0297 (7)	0.0024 (5)	−0.0120 (5)	0.0002 (5)
O6	0.0307 (7)	0.0246 (6)	0.0267 (6)	−0.0017 (5)	−0.0094 (5)	0.0035 (5)
O7	0.0314 (7)	0.0243 (6)	0.0381 (7)	0.0046 (5)	−0.0067 (6)	0.0088 (6)
O8	0.0291 (7)	0.0228 (6)	0.0241 (6)	−0.0017 (5)	0.0064 (5)	−0.0022 (5)
O9	0.0249 (6)	0.0238 (6)	0.0239 (6)	−0.0066 (5)	0.0036 (5)	0.0035 (5)
N1	0.0195 (6)	0.0119 (6)	0.0186 (6)	−0.0005 (5)	0.0004 (5)	−0.0004 (5)
N2	0.0275 (8)	0.0157 (7)	0.0269 (8)	−0.0054 (5)	0.0019 (6)	−0.0033 (6)
N3	0.0256 (8)	0.0194 (7)	0.0227 (7)	−0.0059 (6)	0.0025 (6)	−0.0006 (6)
C1	0.0182 (7)	0.0155 (7)	0.0149 (7)	−0.0014 (6)	−0.0009 (6)	−0.0006 (6)
C2	0.0177 (8)	0.0168 (8)	0.0184 (8)	0.0011 (6)	0.0010 (6)	−0.0016 (6)
C3	0.0212 (8)	0.0121 (7)	0.0181 (8)	0.0000 (6)	−0.0037 (6)	0.0006 (6)
C4	0.0175 (8)	0.0178 (7)	0.0141 (7)	−0.0045 (6)	−0.0001 (6)	0.0016 (6)
C5	0.0162 (8)	0.0215 (8)	0.0148 (7)	0.0009 (6)	0.0015 (6)	−0.0031 (6)
C6	0.0195 (8)	0.0156 (7)	0.0184 (8)	0.0008 (6)	−0.0006 (6)	0.0002 (6)
C7	0.0264 (9)	0.0177 (8)	0.0342 (10)	0.0026 (6)	0.0033 (8)	−0.0017 (7)
C8	0.0290 (9)	0.0268 (9)	0.0178 (8)	0.0008 (7)	0.0028 (7)	0.0030 (7)
C9	0.0315 (9)	0.0257 (9)	0.0267 (9)	0.0104 (7)	0.0078 (8)	0.0010 (7)
C10	0.0185 (8)	0.0138 (7)	0.0171 (8)	0.0009 (6)	0.0027 (6)	0.0005 (6)
C11	0.0169 (8)	0.0155 (7)	0.0158 (7)	−0.0005 (6)	0.0042 (6)	0.0007 (5)
C12	0.0212 (8)	0.0157 (8)	0.0206 (8)	−0.0015 (6)	0.0031 (6)	0.0012 (6)
C13	0.0185 (8)	0.0188 (8)	0.0192 (8)	−0.0038 (6)	0.0015 (6)	−0.0020 (6)
C14	0.0287 (9)	0.0268 (9)	0.0278 (9)	0.0036 (7)	−0.0089 (7)	−0.0029 (7)
C15	0.0176 (8)	0.0191 (8)	0.0196 (8)	0.0028 (6)	0.0007 (6)	0.0017 (6)
C16	0.0192 (8)	0.0152 (8)	0.0199 (8)	0.0012 (6)	0.0024 (6)	0.0004 (6)
C17	0.0155 (7)	0.0151 (7)	0.0162 (7)	0.0005 (5)	0.0035 (6)	0.0003 (5)
C18	0.0171 (8)	0.0153 (7)	0.0162 (7)	−0.0009 (6)	0.0036 (6)	−0.0010 (6)
C19	0.0195 (8)	0.0160 (8)	0.0169 (8)	−0.0006 (6)	0.0023 (6)	−0.0010 (6)
C20	0.0262 (9)	0.0195 (8)	0.0214 (8)	−0.0008 (7)	−0.0025 (7)	0.0023 (6)
C21	0.0186 (8)	0.0255 (9)	0.0231 (8)	−0.0017 (6)	0.0006 (7)	0.0041 (7)
C22	0.0172 (7)	0.0152 (8)	0.0194 (8)	0.0004 (6)	0.0037 (6)	0.0026 (6)
C23	0.0204 (8)	0.0164 (7)	0.0148 (8)	0.0011 (6)	0.0003 (6)	−0.0007 (6)
C24	0.0184 (8)	0.0156 (7)	0.0166 (8)	−0.0006 (6)	−0.0026 (6)	0.0014 (6)
C25	0.0169 (8)	0.0215 (8)	0.0192 (8)	−0.0009 (6)	−0.0013 (7)	0.0053 (6)
C26	0.0261 (9)	0.0301 (9)	0.0300 (9)	−0.0017 (8)	0.0072 (8)	0.0105 (8)
Cl1	0.0722 (4)	0.0437 (3)	0.0526 (3)	−0.0320 (3)	0.0287 (3)	−0.0187 (3)
Cl2	0.0490 (3)	0.0366 (3)	0.0342 (3)	0.0004 (2)	0.0064 (2)	−0.0110 (2)
C27	0.0350 (11)	0.0262 (9)	0.0417 (11)	−0.0044 (8)	0.0050 (9)	−0.0084 (8)

Geometric parameters (Å, º) top

O1—C3	1.3722 (18)	C9—H9A	0.9800
O1—C7	1.4258 (19)	C9—H9B	0.9800
O2—C4	1.3823 (17)	C9—H9C	0.9800
O2—C8	1.4339 (19)	C10—C11	1.524 (2)
O3—C5	1.3631 (19)	C10—C22	1.535 (2)
O3—C9	1.433 (2)	C10—H10	1.0000
O4—C13	1.3710 (19)	C11—C17	1.394 (2)
O4—C14	1.430 (2)	C11—C12	1.411 (2)
O5—C15	1.3747 (19)	C12—C13	1.368 (2)
O5—C14	1.438 (2)	C12—H12	0.9500
O6—C21	1.371 (2)	C13—C15	1.384 (2)
O6—C20	1.4575 (19)	C14—H14A	0.9900
O7—C21	1.1985 (19)	C14—H14B	0.9900
O8—C25	1.2084 (19)	C15—C16	1.363 (2)
O9—C25	1.3409 (19)	C16—C17	1.411 (2)
O9—C26	1.454 (2)	C16—H16	0.9500
N1—C23	1.340 (2)	C17—C18	1.516 (2)
N1—N2	1.3664 (18)	C18—C19	1.522 (2)
N1—C18	1.4800 (19)	C18—H18	1.0000
N2—N3	1.3057 (19)	C19—C20	1.521 (2)
N3—C24	1.367 (2)	C19—C22	1.528 (2)
C1—C6	1.392 (2)	C19—H19	1.0000
C1—C2	1.396 (2)	C20—H20A	0.9900
C1—C10	1.526 (2)	C20—H20B	0.9900
C2—C3	1.392 (2)	C21—C22	1.515 (2)
C2—H2	0.9500	C22—H22	1.0000
C3—C4	1.398 (2)	C23—C24	1.377 (2)
C4—C5	1.397 (2)	C23—H23	0.9500
C5—C6	1.392 (2)	C24—C25	1.472 (2)
C6—H6	0.9500	C26—H26A	0.9800
C7—H7A	0.9800	C26—H26B	0.9800
C7—H7B	0.9800	C26—H26C	0.9800
C7—H7C	0.9800	Cl1—C27	1.7613 (19)
C8—H8A	0.9800	Cl2—C27	1.775 (2)
C8—H8B	0.9800	C27—H27A	0.9900
C8—H8C	0.9800	C27—H27B	0.9900

C3—O1—C7	117.47 (12)	O4—C14—O5	108.23 (13)
C4—O2—C8	112.53 (12)	O4—C14—H14A	110.1
C5—O3—C9	116.98 (12)	O5—C14—H14A	110.1
C13—O4—C14	106.31 (12)	O4—C14—H14B	110.1
C15—O5—C14	105.43 (12)	O5—C14—H14B	110.1
C21—O6—C20	109.90 (12)	H14A—C14—H14B	108.4
C25—O9—C26	114.00 (12)	C16—C15—O5	128.01 (14)
C23—N1—N2	110.51 (12)	C16—C15—C13	121.57 (15)
C23—N1—C18	130.16 (12)	O5—C15—C13	110.42 (14)
N2—N1—C18	119.31 (12)	C15—C16—C17	117.59 (14)
N3—N2—N1	107.58 (12)	C15—C16—H16	121.2
N2—N3—C24	108.46 (12)	C17—C16—H16	121.2
C6—C1—C2	120.50 (14)	C11—C17—C16	121.13 (14)
C6—C1—C10	121.51 (13)	C11—C17—C18	123.14 (14)
C2—C1—C10	117.91 (13)	C16—C17—C18	115.68 (13)
C3—C2—C1	119.62 (14)	N1—C18—C17	109.06 (12)
C3—C2—H2	120.2	N1—C18—C19	113.12 (13)
C1—C2—H2	120.2	C17—C18—C19	110.17 (12)
O1—C3—C2	125.16 (14)	N1—C18—H18	108.1
O1—C3—C4	114.67 (14)	C17—C18—H18	108.1
C2—C3—C4	120.17 (14)	C19—C18—H18	108.1
O2—C4—C5	120.10 (14)	C20—C19—C18	119.93 (12)
O2—C4—C3	119.95 (13)	C20—C19—C22	100.32 (12)
C5—C4—C3	119.81 (13)	C18—C19—C22	111.58 (13)
O3—C5—C6	125.09 (14)	C20—C19—H19	108.1
O3—C5—C4	114.81 (13)	C18—C19—H19	108.1
C6—C5—C4	120.07 (14)	C22—C19—H19	108.1
C1—C6—C5	119.82 (14)	O6—C20—C19	103.49 (12)
C1—C6—H6	120.1	O6—C20—H20A	111.1
C5—C6—H6	120.1	C19—C20—H20A	111.1
O1—C7—H7A	109.5	O6—C20—H20B	111.1
O1—C7—H7B	109.5	C19—C20—H20B	111.1
H7A—C7—H7B	109.5	H20A—C20—H20B	109.0
O1—C7—H7C	109.5	O7—C21—O6	121.17 (15)
H7A—C7—H7C	109.5	O7—C21—C22	130.67 (15)
H7B—C7—H7C	109.5	O6—C21—C22	108.15 (13)
O2—C8—H8A	109.5	C21—C22—C19	101.14 (13)
O2—C8—H8B	109.5	C21—C22—C10	120.70 (12)
H8A—C8—H8B	109.5	C19—C22—C10	114.36 (13)
O2—C8—H8C	109.5	C21—C22—H22	106.6
H8A—C8—H8C	109.5	C19—C22—H22	106.6
H8B—C8—H8C	109.5	C10—C22—H22	106.6
O3—C9—H9A	109.5	N1—C23—C24	104.66 (13)
O3—C9—H9B	109.5	N1—C23—H23	127.7
H9A—C9—H9B	109.5	C24—C23—H23	127.7
O3—C9—H9C	109.5	N3—C24—C23	108.78 (14)
H9A—C9—H9C	109.5	N3—C24—C25	125.55 (14)
H9B—C9—H9C	109.5	C23—C24—C25	125.63 (14)
C11—C10—C1	110.59 (12)	O8—C25—O9	124.24 (15)
C11—C10—C22	109.26 (12)	O8—C25—C24	122.69 (14)
C1—C10—C22	116.22 (12)	O9—C25—C24	113.07 (14)
C11—C10—H10	106.8	O9—C26—H26A	109.5
C1—C10—H10	106.8	O9—C26—H26B	109.5
C22—C10—H10	106.8	H26A—C26—H26B	109.5
C17—C11—C12	119.80 (14)	O9—C26—H26C	109.5
C17—C11—C10	124.14 (14)	H26A—C26—H26C	109.5
C12—C11—C10	116.03 (12)	H26B—C26—H26C	109.5
C13—C12—C11	117.78 (14)	Cl1—C27—Cl2	111.18 (11)
C13—C12—H12	121.1	Cl1—C27—H27A	109.4
C11—C12—H12	121.1	Cl2—C27—H27A	109.4
C12—C13—O4	128.28 (14)	Cl1—C27—H27B	109.4
C12—C13—C15	122.11 (15)	Cl2—C27—H27B	109.4
O4—C13—C15	109.60 (14)	H27A—C27—H27B	108.0

C23—N1—N2—N3	−0.34 (17)	C13—C15—C16—C17	−0.7 (2)
C18—N1—N2—N3	178.32 (12)	C12—C11—C17—C16	−0.9 (2)
N1—N2—N3—C24	0.55 (17)	C10—C11—C17—C16	177.31 (13)
C6—C1—C2—C3	−1.0 (2)	C12—C11—C17—C18	176.30 (13)
C10—C1—C2—C3	175.82 (14)	C10—C11—C17—C18	−5.5 (2)
C7—O1—C3—C2	11.4 (2)	C15—C16—C17—C11	1.2 (2)
C7—O1—C3—C4	−168.31 (14)	C15—C16—C17—C18	−176.13 (14)
C1—C2—C3—O1	−178.91 (14)	C23—N1—C18—C17	37.7 (2)
C1—C2—C3—C4	0.7 (2)	N2—N1—C18—C17	−140.67 (13)
C8—O2—C4—C5	92.48 (17)	C23—N1—C18—C19	−85.29 (18)
C8—O2—C4—C3	−91.68 (17)	N2—N1—C18—C19	96.36 (15)
O1—C3—C4—O2	4.1 (2)	C11—C17—C18—N1	−103.10 (16)
C2—C3—C4—O2	−175.64 (14)	C16—C17—C18—N1	74.20 (16)
O1—C3—C4—C5	179.91 (13)	C11—C17—C18—C19	21.6 (2)
C2—C3—C4—C5	0.2 (2)	C16—C17—C18—C19	−161.08 (13)
C9—O3—C5—C6	8.2 (2)	N1—C18—C19—C20	−41.98 (18)
C9—O3—C5—C4	−173.77 (14)	C17—C18—C19—C20	−164.34 (13)
O2—C4—C5—O3	−3.2 (2)	N1—C18—C19—C22	74.75 (15)
C3—C4—C5—O3	−179.03 (14)	C17—C18—C19—C22	−47.60 (17)
O2—C4—C5—C6	174.94 (14)	C21—O6—C20—C19	−22.57 (16)
C3—C4—C5—C6	−0.9 (2)	C18—C19—C20—O6	160.39 (13)
C2—C1—C6—C5	0.3 (2)	C22—C19—C20—O6	37.97 (14)
C10—C1—C6—C5	−176.39 (14)	C20—O6—C21—O7	177.91 (16)
O3—C5—C6—C1	178.54 (14)	C20—O6—C21—C22	−3.11 (17)
C4—C5—C6—C1	0.6 (2)	O7—C21—C22—C19	−153.98 (19)
C6—C1—C10—C11	45.76 (19)	O6—C21—C22—C19	27.17 (16)
C2—C1—C10—C11	−131.05 (14)	O7—C21—C22—C10	−26.7 (3)
C6—C1—C10—C22	−79.53 (18)	O6—C21—C22—C10	154.47 (14)
C2—C1—C10—C22	103.66 (16)	C20—C19—C22—C21	−38.84 (14)
C1—C10—C11—C17	−114.25 (16)	C18—C19—C22—C21	−166.96 (12)
C22—C10—C11—C17	14.9 (2)	C20—C19—C22—C10	−170.17 (13)
C1—C10—C11—C12	63.98 (17)	C18—C19—C22—C10	61.71 (17)
C22—C10—C11—C12	−166.88 (13)	C11—C10—C22—C21	−163.16 (13)
C17—C11—C12—C13	−0.1 (2)	C1—C10—C22—C21	−37.2 (2)
C10—C11—C12—C13	−178.42 (14)	C11—C10—C22—C19	−42.11 (17)
C11—C12—C13—O4	−179.74 (15)	C1—C10—C22—C19	83.85 (16)
C11—C12—C13—C15	0.7 (2)	N2—N1—C23—C24	−0.01 (17)
C14—O4—C13—C12	−179.90 (17)	C18—N1—C23—C24	−178.48 (15)
C14—O4—C13—C15	−0.29 (18)	N2—N3—C24—C23	−0.56 (18)
C13—O4—C14—O5	0.88 (18)	N2—N3—C24—C25	−178.25 (14)
C15—O5—C14—O4	−1.12 (18)	N1—C23—C24—N3	0.34 (17)
C14—O5—C15—C16	−179.58 (17)	N1—C23—C24—C25	178.03 (14)
C14—O5—C15—C13	0.96 (18)	C26—O9—C25—O8	−3.0 (2)
C12—C13—C15—C16	−0.3 (3)	C26—O9—C25—C24	176.46 (13)
O4—C13—C15—C16	−179.94 (14)	N3—C24—C25—O8	178.28 (16)
C12—C13—C15—O5	179.20 (14)	C23—C24—C25—O8	1.0 (3)
O4—C13—C15—O5	−0.43 (19)	N3—C24—C25—O9	−1.2 (2)
O5—C15—C16—C17	179.92 (15)	C23—C24—C25—O9	−178.50 (15)

Experimental details

Crystal data
Chemical formula	C₂₆H₂₅N₃O₉·CH₂Cl₂
M_r	608.42
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	113
a, b, c (Å)	10.377 (2), 12.639 (3), 20.463 (4)
V (Å³)	2683.9 (10)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.30
Crystal size (mm)	0.28 × 0.24 × 0.12

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.920, 0.965
No. of measured, independent and observed [I > 2σ(I)] reflections	22515, 6397, 5768
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.079, 1.01
No. of reflections	6397
No. of parameters	374
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.34
Absolute structure	Flack (1983), 2800 Friedel pairs
Absolute structure parameter	0.04 (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).

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