PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2008 January 1; 64(Pt 1): o89–o90.
Published online 2007 December 6. doi:  10.1107/S1600536807063180
PMCID: PMC2915045

Redetermination of dihydro­artemisinin at 103 (2) K

Abstract

Tthe structure of the title compound, C15H24O5, has been redetermined at 103 (2) K, with much improved precision. The title compound was first reported by Luo, Yeh, Brossi, Flippen-Anderson & Gillardi [Helv. Chim. Acta (1984). 67, 1515–1522]. It is a derivative of the anti­malaria compound artemisinin and consists primarily of three substituted ring systems fused together. A cyclo­hexane ring (with a distorted chair conformation), is fused to a tetra­hydro­pyran group (also with a distorted chair conformation), and is adjacent to an oxacyclo­heptane unit containing an endoperoxide bridge. This gives the mol­ecule a unique three-dimensional arrangement. The crystal packing is stabilized by inter­molecular C–H(...)O and O–H(...)O inter­actions between an H atom from the cyclo­hexane ring and an O atom from the endoperoxide bridge, as well as between the hydroxyl H atom and an O atom from a tetra­hydro­pyran ring.

Related literature

For crystal structures of similar compounds, see: Flippen-Anderson et al. (1989 [triangle]), Yue et al. (2006 [triangle]), Li et al. (2006 [triangle]); Karle & Lin (1995 [triangle]); Brossi et al. (1988 [triangle]). For the biological activity of artemisinin derivatives in vitro and in vivo, see: Li et al. (2001 [triangle]); Yang et al. (1997 [triangle]); Grace et al. (1998 [triangle]); Maggs et al. (2000 [triangle]). For endoperoxide sesquiterpene lactone derivatives, see: Venugopalan et al. (1995 [triangle]); Wu et al. (2001 [triangle]); Saxena et al. (2003 [triangle]). For the synthesis of artemisinin and its derivatives, see: Lui et al. (1979 [triangle]); Liu (1980 [triangle]); Robert et al. (2001 [triangle]). For related literature, see: Allen et al. (1987 [triangle]); Cremer & Pople (1975 [triangle]); Lisgarten et al. (1998 [triangle]); Qinghaosu Research Group (1980 [triangle]); Shen & Zhuang (1984 [triangle]); Wu & Li (1995 [triangle]); Luo et al. (1984 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-00o89-scheme1.jpg

Experimental

Crystal data

  • C15H24O5
  • M r = 284.34
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-00o89-efi1.jpg
  • a = 5.5910 (6) Å
  • b = 14.1309 (14) Å
  • c = 18.8062 (19) Å
  • V = 1485.8 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 103 (2) K
  • 0.67 × 0.11 × 0.09 mm

Data collection

  • Bruker APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.940, T max = 0.992
  • 16573 measured reflections
  • 2475 independent reflections
  • 2130 reflections with I > 2σ(I)
  • R int = 0.044

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.100
  • S = 1.06
  • 2475 reflections
  • 185 parameters
  • H-atom parameters constrained
  • Δρmax = 0.37 e Å−3
  • Δρmin = −0.22 e Å−3

Data collection: APEX2 (Bruker, 2006 [triangle]); cell refinement: APEX2; data reduction: SAINT (Bruker, 2006 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 [triangle]); molecular graphics: SHELXTL (Bruker, 2000 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807063180/fj2084sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807063180/fj2084Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

RJB acknowledges the Laboratory for the Structure of Matter at the Naval Research Laboratory, Washington DC, USA, for access to their diffractometers. BN thanks Strides Arco Labs, Mangalore, India, for a gift sample of the title compound.

supplementary crystallographic information

Comment

Artemisinin and its derivatives, dihydroartemisinin, artemether, arteether and artesunate are antimalarial drugs which possess bioactivity with less toxicity (Wu & Li, 1995). Artemisinin is isolated from the leaves of plant Artemisia annua (Qinghao). It is a sesquiterpene lactone with an endoperoxide linkage. Artemisinin derivatives are more potent than artemisinin and are active by virtue of the endoperoxide. Their activity against strains of the parasite that had become resistant to conventional chloroquine therapy and the ability due to its lipophilic structure, to cross the blood brain barrier, it was particularly effective for the deadly cerebral malaria (Shen & Zhuang, 1984). Because of their shorter life time and decreasing activity, they are used in combination with other antimalarial drugs. The notable activity of artemisinin derivatives in vitro and in vivo has been reported in literature (Li et al. 2001 & Yang et al. 1997). However, some derivatives of artimisinine showed moderate cytotoxicity in vitro. The electronegativity and bulk of the substituents that attached to the aryl group plays an insignificant role in cytotoxicity. The antimalarial activity and cytotoxicity of some sesquiterpenoids has been reported in the literature (Venugopalan et al. 1995; Wu et al. 2001 and Saxena et al. 2003). The endoperoxide moiety present in these compounds plays an important role in antimalarial activity. Its 1,2,4 trioxane ring is unique in nature. After being opened in the plasmodium it liberates singlet oxygen and forms free radical which inturn produces oxidative damage to the parasites membrane. Artemisinin is hydrophobic in nature and are partitioned into the membrane of the plasmodium. The structures of the antimalarials dihydroqinghaosu, artemether and artesunic acid derived from qinghaosu were elaborated by 1H-NMR spectroscopy, and supported with X-ray data have been reported (Luo et al. 1984). The crystal structure of an ether dimer of deoxydihydroqinghaosu, a potential metabolite of the antimalarial arteether is reported (Flippen-Anderson et al. 1989). The correlation of the crystal structures of diastereomeric artemisinin derivatives with their proton NMR spectra in CDCl3 is reported (Karle & Lin, 1995). The crystal structure of artemisinin is reported (Lisgarten et al. 1998). The crystal structure of a dimer of α- and β-dihydroartemisinin (Yue et al. 2006) and that of 9,10-dehydrodeoxyartemisin is recently reported (Li et al. 2006). The synthesis of artemisinin and its derivatives are described (Lui et al. 1979; Lui, 1980; Robert et al. 2001). The synthesis and antimalarial properties of arteether have been reported (Brossi et al. 1988). β-Arteether (AE) is an endoperoxide sesquiterpene lactone derivative currently being developed for the treatment of severe, complicated malaria caused by multidrug-resistant Plasmodium falciparum (Grace et al. 1998). β-Artemether (AM), the O-methyl ether prodrug of dihydroartemisinin (DHA), is an endoperoxide antimalarial (Maggs et al. 2000). In view of the importance of the title compound, (I) C15H24O5, as n antimalarial drug, this paper reports a redetermination of the crystal structure first reported by Luo et al. (1984).

The six-membered cyclohexane ring (A, C1—C6) is a slightly distorted chair, with Cremer & Pople (1975) puckering parameters Q, θ and [var phi] of 0.553 (2) Å, 4.8 (2)° and 170 (3)°, respectively. The tetrahydropyran group (D, C1—C2—C12—C11—O2—C10) is also a slightly distorted chair configuration with puckering parameters Q, θ and [var phi] of 0.539 (2) Å, 2.7 (2)° and 227 (4)°, respectively. For an ideal chair θ has a value of 0 or 180°. Similar conformations for rings A and D were found in 9,10-dehydrodeoxyartemisinin (Shu-Hui Li et al. 2006). The seven-membered ring B (C1/C6—C9/O1—C10) contains the important peroxy linkage [O3—O4 = 1.471 (2) Å]. The six-membered ring C (O1—C9—O3—O4—C1—C10) which contains both an oxygen bridge and a peroxy bridge is best described by a twist-boat conformation with puckering parameters Q, θ and [var phi] of 0.750 (2) Å, 85.26 (15)° and 96.58 (11)°, respectively. For an ideal twist-boat conformation, θ and [var phi] are 90° and (60n + 30)°, respectively. This conformation is consistent with both 9,10-dehydrodeoxyartemisinin (Li et al. (2006) and dihydroartemisinin (Qinghaosu Research Group, 1980).

Experimental

The title compound (C15H24O5)was obtained in the pure form from Strides Arco Labs, Mangalore, India. X-ray diffraction quality crystals were grown from acetone-methylacetoacetate (1:1). (m.p.: 413 K).

Refinement

All H atoms were initially located in a difference Fourier map. The methyl H atoms were then constrained to an ideal geometry with C—H distances of 0.98 Å and Uiso(H) = 1.5Ueq(C), but each group was allowed to rotate freely about its C—C bond. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with C—H distances in the range 0.98–1.00 Å and Uiso(H) = 1.17–1.22Ueq(C). The hydroxyl H was idealized with an O—H distance of 0.84Å and Uiso(H) = 1.21Ueq(O). Because no strong anomalous scattering atoms are present, the Friedel pairs were merged in the refinement.

Figures

Fig. 1.
ORTEP view of dihydroartemisinine, (I), showing the atom numbering scheme and 50% probability displacement ellipsoids.
Fig. 2.
The molecular packing for I viewed down the c axis. Dashed lines indicate C–H···O and O–H···O intermolecular hydrogen bonds.

Crystal data

C15H24O5F000 = 616
Mr = 284.34Dx = 1.271 Mg m3
Orthorhombic, P212121Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 4650 reflections
a = 5.5910 (6) Åθ = 2.6–29.6º
b = 14.1309 (14) ŵ = 0.09 mm1
c = 18.8062 (19) ÅT = 103 (2) K
V = 1485.8 (3) Å3Needle, colorless
Z = 40.67 × 0.11 × 0.09 mm

Data collection

Bruker APEXII CCD area-detector diffractometer2475 independent reflections
Radiation source: fine-focus sealed tube2130 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.044
T = 103(2) Kθmax = 30.5º
[var phi] and ω scansθmin = 1.8º
Absorption correction: multi-scan(SADABS; Sheldrick, 1996)h = −5→7
Tmin = 0.940, Tmax = 0.992k = −19→19
16573 measured reflectionsl = −26→26

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.100  w = 1/[σ2(Fo2) + (0.0434P)2 + 0.5149P] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.002
2475 reflectionsΔρmax = 0.37 e Å3
185 parametersΔρmin = −0.22 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

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)

xyzUiso*/Ueq
O10.2493 (3)0.35457 (10)0.85285 (7)0.0212 (3)
O20.1910 (3)0.31049 (9)0.96710 (6)0.0187 (3)
O3−0.1579 (3)0.36796 (11)0.87194 (7)0.0250 (3)
O4−0.1419 (3)0.45439 (10)0.91529 (7)0.0229 (3)
O50.4123 (3)0.34511 (9)1.06918 (7)0.0198 (3)
H50.49530.29591.06480.024*
C10.1042 (4)0.47570 (13)0.93520 (9)0.0178 (4)
C20.0886 (4)0.50052 (13)1.01511 (9)0.0195 (4)
H2A−0.04580.54671.02050.023*
C30.3158 (4)0.55071 (13)1.04118 (10)0.0238 (4)
H3A0.29420.57011.09140.029*
H3B0.45230.50621.03900.029*
C40.3716 (5)0.63737 (13)0.99635 (10)0.0269 (5)
H4A0.51980.66741.01420.032*
H4B0.23980.68371.00120.032*
C50.4035 (4)0.61214 (13)0.91802 (10)0.0225 (4)
H5A0.54120.56730.91400.027*
C60.1797 (4)0.56209 (13)0.88957 (9)0.0195 (4)
H6A0.04590.60890.89250.023*
C70.2078 (4)0.53662 (14)0.81060 (9)0.0245 (4)
H7A0.19860.59570.78250.029*
H7B0.36970.50980.80350.029*
C80.0260 (5)0.46691 (15)0.78064 (10)0.0269 (5)
H8A0.06210.45580.72980.032*
H8B−0.13530.49550.78360.032*
C90.0230 (4)0.37149 (15)0.81945 (10)0.0247 (4)
C100.2609 (4)0.38836 (12)0.92316 (9)0.0163 (4)
H10A0.43060.40510.93430.020*
C110.1826 (4)0.32865 (13)1.04225 (9)0.0184 (4)
H11A0.11590.27131.06630.022*
C120.0176 (4)0.41122 (14)1.05737 (9)0.0200 (4)
H12A−0.14440.39221.04000.024*
C130.4636 (5)0.70119 (16)0.87466 (12)0.0342 (6)
H13A0.60480.73210.89500.051*
H13B0.32780.74500.87600.051*
H13C0.49670.68330.82530.051*
C14−0.0293 (6)0.28799 (17)0.77187 (11)0.0364 (6)
H14A−0.04910.23100.80100.055*
H14B0.10390.27880.73870.055*
H14C−0.17650.29990.74510.055*
C15−0.0068 (5)0.42857 (16)1.13739 (10)0.0299 (5)
H15A−0.06950.37151.16040.045*
H15B−0.11690.48141.14560.045*
H15C0.15030.44391.15740.045*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0215 (8)0.0257 (6)0.0163 (5)−0.0011 (6)0.0014 (6)−0.0038 (5)
O20.0211 (7)0.0181 (6)0.0168 (6)−0.0022 (6)−0.0012 (6)0.0004 (5)
O30.0209 (8)0.0333 (7)0.0208 (6)−0.0074 (6)−0.0017 (6)0.0001 (6)
O40.0142 (7)0.0317 (7)0.0228 (6)0.0013 (6)−0.0024 (5)−0.0013 (6)
O50.0172 (7)0.0190 (6)0.0232 (6)0.0012 (5)−0.0047 (6)0.0003 (5)
C10.0132 (9)0.0230 (8)0.0171 (8)0.0018 (7)−0.0005 (7)−0.0016 (7)
C20.0197 (10)0.0210 (8)0.0180 (8)0.0061 (8)0.0005 (8)−0.0014 (6)
C30.0315 (12)0.0206 (8)0.0194 (8)−0.0016 (9)−0.0056 (9)0.0010 (7)
C40.0385 (13)0.0177 (8)0.0245 (9)−0.0005 (9)−0.0043 (9)−0.0011 (7)
C50.0267 (11)0.0185 (8)0.0223 (8)−0.0003 (8)−0.0016 (8)0.0033 (7)
C60.0196 (10)0.0191 (8)0.0198 (8)0.0021 (7)−0.0019 (8)0.0013 (7)
C70.0299 (12)0.0257 (9)0.0179 (8)−0.0017 (9)0.0000 (8)0.0036 (7)
C80.0293 (13)0.0346 (11)0.0168 (8)−0.0045 (10)−0.0052 (8)0.0032 (8)
C90.0245 (11)0.0323 (10)0.0175 (8)−0.0066 (9)−0.0010 (8)−0.0005 (8)
C100.0165 (9)0.0170 (7)0.0156 (7)−0.0003 (7)−0.0006 (7)−0.0007 (6)
C110.0160 (9)0.0230 (8)0.0161 (7)−0.0023 (8)−0.0016 (7)0.0020 (7)
C120.0169 (10)0.0265 (9)0.0165 (8)0.0011 (8)0.0016 (7)0.0016 (7)
C130.0446 (15)0.0275 (10)0.0304 (10)−0.0116 (11)−0.0032 (11)0.0058 (9)
C140.0470 (17)0.0386 (12)0.0234 (10)−0.0151 (12)−0.0042 (11)−0.0034 (9)
C150.0351 (14)0.0370 (11)0.0177 (9)0.0037 (10)0.0051 (9)−0.0001 (8)

Geometric parameters (Å, °)

O1—C101.407 (2)C6—C71.536 (3)
O1—C91.432 (3)C6—H6A1.0000
O2—C101.431 (2)C7—C81.524 (3)
O2—C111.437 (2)C7—H7A0.9900
O3—C91.414 (3)C7—H7B0.9900
O3—O41.471 (2)C8—C91.533 (3)
O4—C11.457 (2)C8—H8A0.9900
O5—C111.400 (2)C8—H8B0.9900
O5—H50.8400C9—C141.509 (3)
C1—C101.531 (3)C10—H10A1.0000
C1—C21.546 (2)C11—C121.514 (3)
C1—C61.551 (3)C11—H11A1.0000
C2—C31.535 (3)C12—C151.531 (3)
C2—C121.543 (3)C12—H12A1.0000
C2—H2A1.0000C13—H13A0.9800
C3—C41.519 (3)C13—H13B0.9800
C3—H3A0.9900C13—H13C0.9800
C3—H3B0.9900C14—H14A0.9800
C4—C51.526 (3)C14—H14B0.9800
C4—H4A0.9900C14—H14C0.9800
C4—H4B0.9900C15—H15A0.9800
C5—C61.533 (3)C15—H15B0.9800
C5—C131.537 (3)C15—H15C0.9800
C5—H5A1.0000
C10—O1—C9113.35 (15)C7—C8—H8A108.9
C10—O2—C11116.08 (13)C9—C8—H8A108.9
C9—O3—O4108.29 (14)C7—C8—H8B108.9
C1—O4—O3111.82 (13)C9—C8—H8B108.9
C11—O5—H5109.5H8A—C8—H8B107.7
O4—C1—C10109.63 (15)O3—C9—O1108.65 (14)
O4—C1—C2104.10 (15)O3—C9—C14104.33 (18)
C10—C1—C2111.04 (14)O1—C9—C14107.5 (2)
O4—C1—C6106.12 (15)O3—C9—C8111.78 (19)
C10—C1—C6113.38 (16)O1—C9—C8110.25 (17)
C2—C1—C6112.01 (15)C14—C9—C8114.03 (16)
C3—C2—C12115.21 (16)O1—C10—O2105.60 (13)
C3—C2—C1111.63 (17)O1—C10—C1112.70 (14)
C12—C2—C1109.25 (15)O2—C10—C1112.21 (15)
C3—C2—H2A106.8O1—C10—H10A108.7
C12—C2—H2A106.8O2—C10—H10A108.7
C1—C2—H2A106.8C1—C10—H10A108.7
C4—C3—C2111.42 (17)O5—C11—O2110.82 (16)
C4—C3—H3A109.3O5—C11—C12111.27 (15)
C2—C3—H3A109.3O2—C11—C12110.01 (15)
C4—C3—H3B109.3O5—C11—H11A108.2
C2—C3—H3B109.3O2—C11—H11A108.2
H3A—C3—H3B108.0C12—C11—H11A108.2
C3—C4—C5111.80 (16)C11—C12—C15111.25 (16)
C3—C4—H4A109.3C11—C12—C2112.14 (16)
C5—C4—H4A109.3C15—C12—C2113.47 (17)
C3—C4—H4B109.3C11—C12—H12A106.5
C5—C4—H4B109.3C15—C12—H12A106.5
H4A—C4—H4B107.9C2—C12—H12A106.5
C4—C5—C6110.45 (18)C5—C13—H13A109.5
C4—C5—C13110.27 (16)C5—C13—H13B109.5
C6—C5—C13111.78 (17)H13A—C13—H13B109.5
C4—C5—H5A108.1C5—C13—H13C109.5
C6—C5—H5A108.1H13A—C13—H13C109.5
C13—C5—H5A108.1H13B—C13—H13C109.5
C5—C6—C7111.22 (18)C9—C14—H14A109.5
C5—C6—C1113.09 (15)C9—C14—H14B109.5
C7—C6—C1112.24 (15)H14A—C14—H14B109.5
C5—C6—H6A106.6C9—C14—H14C109.5
C7—C6—H6A106.6H14A—C14—H14C109.5
C1—C6—H6A106.6H14B—C14—H14C109.5
C8—C7—C6116.15 (18)C12—C15—H15A109.5
C8—C7—H7A108.2C12—C15—H15B109.5
C6—C7—H7A108.2H15A—C15—H15B109.5
C8—C7—H7B108.2C12—C15—H15C109.5
C6—C7—H7B108.2H15A—C15—H15C109.5
H7A—C7—H7B107.4H15B—C15—H15C109.5
C7—C8—C9113.55 (17)
C9—O3—O4—C1−45.32 (18)O4—O3—C9—C14−172.27 (16)
O3—O4—C1—C10−15.82 (18)O4—O3—C9—C8−48.58 (19)
O3—O4—C1—C2−134.68 (13)C10—O1—C9—O3−32.1 (2)
O3—O4—C1—C6106.97 (15)C10—O1—C9—C14−144.41 (16)
O4—C1—C2—C3−164.53 (15)C10—O1—C9—C890.75 (18)
C10—C1—C2—C377.58 (19)C7—C8—C9—O396.3 (2)
C6—C1—C2—C3−50.3 (2)C7—C8—C9—O1−24.6 (2)
O4—C1—C2—C1266.88 (19)C7—C8—C9—C14−145.6 (2)
C10—C1—C2—C12−51.0 (2)C9—O1—C10—O292.17 (17)
C6—C1—C2—C12−178.90 (17)C9—O1—C10—C1−30.7 (2)
C12—C2—C3—C4179.84 (17)C11—O2—C10—O1−178.37 (16)
C1—C2—C3—C454.5 (2)C11—O2—C10—C1−55.2 (2)
C2—C3—C4—C5−58.2 (3)O4—C1—C10—O156.06 (19)
C3—C4—C5—C656.9 (2)C2—C1—C10—O1170.53 (16)
C3—C4—C5—C13−179.1 (2)C6—C1—C10—O1−62.3 (2)
C4—C5—C6—C7179.67 (16)O4—C1—C10—O2−63.01 (18)
C13—C5—C6—C756.5 (2)C2—C1—C10—O251.5 (2)
C4—C5—C6—C1−53.0 (2)C6—C1—C10—O2178.61 (14)
C13—C5—C6—C1−176.14 (18)C10—O2—C11—O5−67.1 (2)
O4—C1—C6—C5163.26 (15)C10—O2—C11—C1256.3 (2)
C10—C1—C6—C5−76.35 (19)O5—C11—C12—C15−60.2 (2)
C2—C1—C6—C550.3 (2)O2—C11—C12—C15176.61 (17)
O4—C1—C6—C7−69.9 (2)O5—C11—C12—C268.1 (2)
C10—C1—C6—C750.5 (2)O2—C11—C12—C2−55.1 (2)
C2—C1—C6—C7177.11 (18)C3—C2—C12—C11−72.8 (2)
C5—C6—C7—C8166.05 (18)C1—C2—C12—C1153.8 (2)
C1—C6—C7—C838.2 (3)C3—C2—C12—C1554.3 (2)
C6—C7—C8—C9−58.4 (3)C1—C2—C12—C15−179.07 (18)
O4—O3—C9—O173.30 (18)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O5—H5···O2i0.841.952.7799 (19)168
C5—H5A···O4ii1.002.383.381 (3)175

Symmetry codes: (i) x+1/2, −y+1/2, −z+2; (ii) x+1, y, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FJ2084).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Brossi, A., Venugopalan, B., Dominguez Gerpe, L., Yeh, H. J. C., Flippen-Anderson, J. L., Buchs, P., Luo, X. D., Milhousand, W. & Peters, W. (1988). J. Med. Chem.31, 645–650. [PubMed]
  • Bruker (2000). SHELXTL Version 6.10. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Bruker (2006). APEX2 Version 2.0-2. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Flippen-Anderson, J. L., George, C., Gilardi, R., Yu, Q.-S., Dominguez, L. & Brossi, A. (1989). Acta Cryst. C45, 292–294. [PubMed]
  • Grace, J. M., Aguilar, A. J., Trotman, K. M. & Brewer, T. G. (1998). Drug. Metab. Dispos.26, 313–317. [PubMed]
  • Karle, J. M. & Lin, Ai. J. (1995). Acta Cryst. B51, 1063–1068.
  • Li, Y., Shan, F., Wu, J. M., Wu, G. S., Ding, J., Xiao, D., Yang, W. Y., Atassi, G., Leonce, S., Caignard, D. H. & Renard, P. (2001). Bioorg. Med. Chem. Lett.11, 5–8. [PubMed]
  • Li, S.-H., Yue, Z.-Y., Gao, P. & Yan, P.-F. (2006). Acta Cryst. E62, o1898–o1900.
  • Lisgarten, J., Potter, B. S., Bantuzeko, C. & Palmer, A. (1998). J. Chem. Cryst.28, 539–542.
  • Liu, X. (1980). Chin. Pharm. Bull.15, 183–183.
  • Lui, J.-M., Ni, M.-Y., Fan, Y.-E., Tu, Y.-Y., Wu, Z.-H., Wu, Y.-L. & Chou, W.-S. (1979). Acta Chim. Sinica, 37, 129–141.
  • Luo, X. D., Yeh, H. J. C., Brossi, A., Flippen-Anderson, J. L. & Gillardi, R. (1984). Helv. Chim. Acta, 67, 1515–1522.
  • Maggs, J. L., Bishop, L. P. D., Edwards, G., O’Neill, P. M., Ward, S. A., Winstanley, P. A. & Park, K. (2000). Drug. Metab. Dispos.28, 209–217. [PubMed]
  • Qinghaosu Research Group (1980). Sci. Sin. (Engl. Ed.), 23, 380–396.
  • Robert, A., Benoit-Vical, F., Dechy-Cabaret, O. & Meunier, B. (2001). Pure Appl. Chem.73, 1173–1188.
  • Saxena, S., Pant, N., Jain, D. C. & Bhakuni, R. S. (2003). Curr. Sci.85, 1314–1329.
  • Sheldrick, G. M. (1990). Acta Cryst. A46, 467–473.
  • Sheldrick, G. M. (1996). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (1997). SHELXL97 University of Göttingen, Germany. [PubMed]
  • Shen, C. C. & Zhuang, L. (1984). Med. Res. Rev.4, 57–59. [PubMed]
  • Venugopalan, B., Karnik, P. J., Bapat, C. J., Chatterjee, D. K., Iyer, N. & Lepcha, D. (1995). Eur. J. Med. Chem.30, 697–706.
  • Wu, Y.-L. & Li, Y. (1995). Med. Chem. Res.5, 569–586.
  • Wu, J. M., Shan, F., Wu, G. S., Ying, L., Ding, J., Xiao, D., Han, J.-X., Atassi, G., Leonce, S., Caignard, D. H. & Renard, P. (2001). Eur. J. Med. Chem.36, 469–479. [PubMed]
  • Yang, X. P., Pan, Q. C., Liang, Y.-G. & Zikang, Y.-L. (1997). Cancer, 16, 186–187.
  • Yue, Z.-Y., Li, S.-H., Gao, P., Zhang, J.-H. & Yan, P.-F. (2006). Acta Cryst. C62, o281–o282. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography