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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 64| Part 1| January 2008| Pages o89-o90
https://doi.org/10.1107/S1600536807063180

Redetermination of di­hydro­artemisinin at 103 (2) K

Jerry P. Jasinski,a* Ray J. Butcher,b H. S. Yathirajan,c B. Narayanad and T. V. Sreevidyad

aDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, bDepartment of Chemistry, Howard University, 525 College Street NW, Washington DC 20059, USA, cDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India, and dDepartment of Studies in Chemistry, Mangalore University, Mangalagangotri 574199, India
*Correspondence e-mail: jjasinski@keene.edu

(Received 18 November 2007; accepted 25 November 2007; online 6 December 2007)

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[Flippen-Anderson, J. L., George, C., Gilardi, R., Yu, Q.-S., Dominguez, L. & Brossi, A. (1989). Acta Cryst. C45, 292-294.]), Yue et al. (2006[Yue, Z.-Y., Li, S.-H., Gao, P., Zhang, J.-H. & Yan, P.-F. (2006). Acta Cryst. C62, o281-o282.]), Li et al. (2006[Li, S.-H., Yue, Z.-Y., Gao, P. & Yan, P.-F. (2006). Acta Cryst. E62, o1898-o1900.]); Karle & Lin (1995[Karle, J. M. & Lin, Ai. J. (1995). Acta Cryst. B51, 1063-1068.]); Brossi et al. (1988[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.]). For the biological activity of artemisinin derivatives in vitro and in vivo, see: Li et al. (2001[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.]); Yang et al. (1997[Yang, X. P., Pan, Q. C., Liang, Y.-G. & Zikang, Y.-L. (1997). Cancer, 16, 186-187.]); Grace et al. (1998[Grace, J. M., Aguilar, A. J., Trotman, K. M. & Brewer, T. G. (1998). Drug. Metab. Dispos. 26, 313-317.]); Maggs et al. (2000[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.]). For endoperoxide sesquiterpene lactone derivatives, see: Venugopalan et al. (1995[Venugopalan, B., Karnik, P. J., Bapat, C. J., Chatterjee, D. K., Iyer, N. & Lepcha, D. (1995). Eur. J. Med. Chem. 30, 697-706.]); Wu et al. (2001[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.]); Saxena et al. (2003[Saxena, S., Pant, N., Jain, D. C. & Bhakuni, R. S. (2003). Curr. Sci. 85, 1314-1329.]). For the synthesis of artemisinin and its derivatives, see: Lui et al. (1979[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.]); Liu (1980[Liu, X. (1980). Chin. Pharm. Bull. 15, 183-183.]); Robert et al. (2001[Robert, A., Benoit-Vical, F., Dechy-Cabaret, O. & Meunier, B. (2001). Pure Appl. Chem. 73, 1173-1188.]). For related literature, see: Allen et al. (1987[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.]); Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]); Lisgarten et al. (1998[Lisgarten, J., Potter, B. S., Bantuzeko, C. & Palmer, A. (1998). J. Chem. Cryst. 28, 539-542.]); Qinghaosu Research Group (1980[Qinghaosu Research Group (1980). Sci. Sin. (Engl. Ed.), 23, 380-396.]); Shen & Zhuang (1984[Shen, C. C. & Zhuang, L. (1984). Med. Res. Rev. 4, 57-59.]); Wu & Li (1995[Wu, Y.-L. & Li, Y. (1995). Med. Chem. Res. 5, 569-586.]); Luo et al. (1984[Luo, X. D., Yeh, H. J. C., Brossi, A., Flippen-Anderson, J. L. & Gillardi, R. (1984). Helv. Chim. Acta, 67, 1515-1522.]).

[Scheme 1]

Experimental

Crystal data

  • C15H24O5

  • Mr = 284.34

  • Orthorhombic, P 21 21 21

  • 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[Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.]) Tmin = 0.940, Tmax = 0.992

  • 16573 measured reflections

  • 2475 independent reflections

  • 2130 reflections with I > 2σ(I)

  • Rint = 0.044
Refinement

  • R[F2 > 2σ(F2)] = 0.038

  • wR(F2) = 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

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O5—H5⋯O2i 0.84 1.95 2.7799 (19) 168
C5—H5A⋯O4ii 1.00 2.38 3.381 (3) 175
Symmetry codes: (i) [x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]; (ii) x+1, y, z.

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2. Version 2.0-2. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: APEX2; data reduction: SAINT (Bruker, 2006[Bruker (2006). APEX2. Version 2.0-2. Bruker AXS Inc., Madison, Wisconsin, USA.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990[Sheldrick, G. M. (1990). Acta Cryst. A46, 467-473.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXL97. University of Göttingen, Germany.]); molecular graphics: SHELXTL (Bruker, 2000[Bruker (2000). SHELXTL. Version 6.10. Bruker AXS Inc., Madison, Wisconsin, USA.]); software used to prepare material for publication: SHELXTL.

Supporting information

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

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536807063180/fj2084Isup2.hkl

checkCIF report


Comment top

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 φ 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 φ 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 φ of 0.750 (2) Å, 85.26 (15)° and 96.58 (11)°, respectively. For an ideal twist-boat conformation, θ and φ 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).

Related literature top

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

Experimental top

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 top

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.

Structure description top

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 φ 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 φ 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 φ of 0.750 (2) Å, 85.26 (15)° and 96.58 (11)°, respectively. For an ideal twist-boat conformation, θ and φ 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).

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

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS90 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2000); software used to prepare material for publication: SHELXTL (Bruker, 2000).

Figures top
[Figure 1] Fig. 1. ORTEP view of dihydroartemisinine, (I), showing the atom numbering scheme and 50% probability displacement ellipsoids.
[Figure 2] 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.
Dihydroartemisinin top
Crystal data top
C15H24O5F(000) = 616
Mr = 284.34Dx = 1.271 Mg m−3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 4650 reflections
a = 5.5910 (6) Åθ = 2.6–29.6°
b = 14.1309 (14) ŵ = 0.09 mm−1
c = 18.8062 (19) ÅT = 103 K
V = 1485.8 (3) Å3Needle, colorless
Z = 40.67 × 0.11 × 0.09 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2475 independent reflections
Radiation source: fine-focus sealed tube2130 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.044
φ and ω scansθmax = 30.5°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		h = −5→7
Tmin = 0.940, Tmax = 0.992k = −19→19
16573 measured reflectionsl = −26→26
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.038Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.100H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0434P)2 + 0.5149P]
where P = (Fo2 + 2Fc2)/3
2475 reflections(Δ/σ)max = 0.002
185 parametersΔρmax = 0.37 e Å−3
0 restraintsΔρmin = −0.22 e Å−3
Crystal data top
C15H24O5V = 1485.8 (3) Å3
Mr = 284.34Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.5910 (6) ŵ = 0.09 mm−1
b = 14.1309 (14) ÅT = 103 K
c = 18.8062 (19) Å0.67 × 0.11 × 0.09 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2475 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		2130 reflections with I > 2σ(I)
Tmin = 0.940, Tmax = 0.992Rint = 0.044
16573 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0380 restraints
wR(F2) = 0.100H-atom parameters constrained
S = 1.06Δρmax = 0.37 e Å−3
2475 reflectionsΔρmin = −0.22 e Å−3
185 parameters
Special details top

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
O10.2493 (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) top
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, º) top
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, º) top
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.

Experimental details

Crystal data
Chemical formulaC15H24O5
Mr284.34
Crystal system, space groupOrthorhombic, P212121
Temperature (K)103
a, b, c (Å)5.5910 (6), 14.1309 (14), 18.8062 (19)
V (Å3)1485.8 (3)
Z4
Radiation typeMo Kα
µ (mm−1)0.09
Crystal size (mm)0.67 × 0.11 × 0.09
Data collection
DiffractometerBruker APEXII CCD area-detector
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.940, 0.992
No. of measured, independent and
observed [I > 2σ(I)] reflections		16573, 2475, 2130
Rint0.044
(sin θ/λ)max (Å−1)0.714
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.100, 1.06
No. of reflections2475
No. of parameters185
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.37, −0.22

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SHELXS90 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 2000).

Hydrogen-bond geometry (Å, º) top
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.
 

Acknowledgements

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.

References

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ISSN: 2056-9890
Volume 64| Part 1| January 2008| Pages o89-o90
https://doi.org/10.1107/S1600536807063180
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