A second polymorph of β-arteether

Jasinski, J.P.; Butcher, R.J.; Yathirajan, H.S.; Narayana, B.; Sreevidya, T.V.

doi:10.1107/S1600536807062812

organic compounds

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ISSN: 2056-9890

Volume 64| Part 3| March 2008| Pages o585-o586

doi:10.1107/S1600536807062812

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A second polymorph of β-arteether

Jerry P. Jasinski,^a ^* Ray J. Butcher,^b H. S. Yathirajan,^c B. Narayana ^d and T. V. Sreevidya ^d

^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 570 006, India, and ^dDepartment of Studies in Chemistry, Mangalore University, Mangalagangotri 574 199, India
^*Correspondence e-mail: jjasinski@keene.edu

(Received 21 November 2007; accepted 24 November 2007; online 13 February 2008)

The crystal structure of the title compound, C₁₇H₂₈O₅, reported here is a polymorph of the structure first reported by El-Feraly, Al-Yahya, Orabi, McPhail & McPhail [J. Nat. Prod. (1992). 55, 878–883]. It is a derivative of the antimalaria compound artemisinin and consists primarily of three substituted ring systems fused together. A cyclohexane ring (distorted chair conformation) fused to a tetrahydropyran group (distorted chair) is adjacent to an oxacycloheptane unit containing an endo-peroxide bridge, giving the molecule its particular three-dimensional arrangement. The crystal packing is stabilized by intermolecular C—H⋯O interactions between an O atom from the endo-peroxide bridge and H atoms from both the cyclohexane and seven-membered oxacycloheptane fused rings, as well as between an O atom and H atom from adjacent tetrahydropyran rings. The two polymorphs have the same space group and similar cell parameters for the a and b axes, but significantly different values for the c axis.

Related literature

For the first polymorph of this compound, see: El-Feraly et al. (1992 ). For crystal structures of similar compounds, see: Brossi et al. (1988 ); Flippen-Anderson et al. (1989 ); Karle & Lin (1995 ); Li et al. (2006 ); Luo et al. (1984 ); Yue et al. (2006 ); Butcher et al. (2007 ); Jasinski et al. (2008 ). For biological activity of artemisinin derivatives in vitro and in vivo, see: Grace et al. (1998 ); Li et al. (2001 ); Maggs et al. (2000 ); Yang et al. (1997 ). For endo-peroxide sesquiterpene lactone derivatives, see: Saxena et al. (2003 ); Venugopalan et al. (1995 ); Wu et al. (2001 ). For the synthesis of artemisinin and its derivatives, see: Lui et al. (1979 ); Liu (1980 ); Robert et al. (2001 ). For related literature, see: Cremer & Pople (1975 ); Lisgarten et al. (1998 ); Qinghaosu Research Group (1980 ); Shen & Zhuang (1984 ); Wu & Li (1995 ).

Experimental

Crystal data

C₁₇H₂₈O₅
M_r = 312.39
Trigonal, P 3₂ 21
a = 10.0253 (6) Å
c = 28.628 (3) Å
V = 2491.8 (3) Å³
Z = 6
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 103 (2) K
0.42 × 0.22 × 0.18 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.963, T_max = 0.984
27842 measured reflections
4935 independent reflections
4517 reflections with I > 2σ(I)
R_int = 0.034

Refinement

R[F² > 2σ(F²)] = 0.040
wR(F²) = 0.101
S = 1.04
4935 reflections
203 parameters
H-atom parameters constrained
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5A⋯O4ⁱ	1.00	2.45	3.3150 (15)	144
C7—H7A⋯O4ⁱ	0.99	2.55	3.4704 (16)	155
Symmetry code: (i) y+1, x, -z.

Data collection: APEX2 (Bruker, 2006 ); cell refinement: APEX2; data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS90 (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 global, I. DOI: 10.1107/S1600536807062812/at2510sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536807062812/at2510Isup2.hkl

checkCIF report

Comment top

Artemisinin and its derivatives, dihydroartemisinin, artemether, arteether and artesunate, are antimalarial drugs which possess bioactivity with reduced toxicity (Wu & Li, 1995). Artemisinin is isolated from the leaves of the plant Artemisia annua (Qinghao). It is a sesquiterpene lactone with an endo-peroxide linkage. Artemisinin derivatives are more potent than artemisinin and are active by virtue of the endo-peroxide. Because of their activity against strains of the parasite that had become resistant to conventional chloroquine therapy and the ability, due to the lipophilic structure, to cross the blood brain barrier, it was particularly effective for the deadly cerebral malaria (Shen & Zhuang, 1984). Because of their shorter lifetime and decreasing activity, they are used in combination with other antimalarial drugs. The notable activity of artemesinin derivatives in vitro and in vivo has been reported in the 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 are attached to the aryl group play 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; Saxena et al., 2003). The endo-peroxide group 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 radicals, which in turn produce oxidative damage of the parasite's membrane. Artemisinin is hydrophobic in nature and is partitioned into the membrane of the plasmodium. The crystal structure of an ether dimer of deoxydihydroqinghaosu, a potential metabolite of the antimalarial arteether, has been reported (Flippen-Anderson et al., 1989). The correlation of the crystal structures of diastereomeric artemisinin derivatives with their proton NMR spectra in CDCl₃ has been reported (Karle & Lin, 1995). The crystal structure of artemisinin has been 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-dehydro-deoxyartemisin has recently been reported (Li et al., 2006). The synthesis of artemisinin and its derivatives have been described (Lui et al., 1979; Liu, 1980; Robert et al., 2001). β-Arteether (AE) is an endo-peroxide 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 endo-peroxide antimalarial (Maggs et al., 2000). In view of the importance of the title compound, C₁₇H₂₈O₅ (I), β-arteether, as an antimalarial drug, this paper describes a new polymorphic form of the crystal structure first reported by El-Feraly et al. (1992), from data measured at 103 (2) K.

A substantial increase in the length of the unit cell c axis from 25.720 to 28.628 Å in the new structure along with a redetermination of the cell constants and the cell volume for (I) at room temperature (296 K) [a = 10.1557 (14), c = 28.714 (4) Å and V = 2564.8 (8) Å³] provides solid support for the recognition of this new polymorphic form for (I). The six-membered cyclohexane ring (C1–C6) is a slightly distorted chair, with Cremer & Pople (1975) puckering parameters Q, θ and ϕ of 0.563 (8) Å, 177.8 (2)° and 20.3 (1)°, respectively (Fig. 1). The tetrahydropyran group (C1/C2/C10–C12/O2) has also a slightly distorted chair conformation with puckering parameters Q, θ and ϕ of 0.518 (5) Å, 176.8 (9)° and 16.9 (6)°, respectively. For an ideal chair θ has a value of 0 or 180°. Similar conformations were found in 9,10-dehydrodeoxyartemisinin (Shu-Hui Li et al., 2006). The seven-membered ring (C1/C6–C9/O1–C10) contains the important peroxy linkage [O3—O4 = 1.4759 (13) Å]. The six-membered ring C (O1/O3/O4/C1/C9/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 0.749 (2) Å, 94.8 (5)° and 276.8 (8)°, respectively. For an ideal twist-boat conformation, θ and ϕ are 90° and (60n + 30)°, respectively. This conformation is consistent with 9,10-dehydrodeoxyartemisinin (Li et al., 2006), dihydroartemisinin (Qinghaosu Research Group, 1980; Jasinski et al., 2008) and artemether (Butcher et al., 2007)

Crystal packing is stabilized by intermolecular C—H···O interactions between hydrogen atoms from the cyclohexane ring (H5A and H7A) and an oxygen atom (O4) from the endo-peroxide bridge (Fig. 2).

Related literature top

For the first polymorph of this compound, see: El-Feraly et al. (1992). For crystal structures of similar compounds, see: Brossi et al. (1988); Flippen-Anderson et al. (1989); Karle & Lin (1995); Li et al. (2006); Luo et al. (1984); Yue et al. (2006); Butcher et al. (2007); Jasinski et al. (2008). For biological activity of artemisinin derivatives in vitro and in vivo, see: Grace et al. (1998); Li et al. (2001); Maggs et al. (2000); Yang et al. (1997). For endo-peroxide sesquiterpene lactone derivatives, see: Saxena et al. (2003); Venugopalan et al. (1995); Wu et al. (2001). For the synthesis of artemisinin and its derivatives, see: Lui et al. (1979); Liu (1980); Robert et al. (2001). For related literature, see: Cremer & Pople (1975); Lisgarten et al. (1998); Qinghaosu Research Group (1980); Shen & Zhuang (1984); Wu & Li (1995).

Experimental top

The title compound (C₁₇H₂₈O₅) was obtained in the pure form from Strides Arco Labs, Mangalore, India. X-ray diffraction quality crystals were grown from acetone [m.p.: 353 K]).

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, 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), 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 intermolecular hydrogen bonds.

β-Arteether top

Crystal data top

C₁₇H₂₈O₅	D_x = 1.249 Mg m⁻³
M_r = 312.39	Mo Kα radiation, λ = 0.71073 Å
Trigonal, P3₂21	Cell parameters from 5075 reflections
Hall symbol: P 32 2"	θ = 2.4–30.0°
a = 10.0253 (6) Å	µ = 0.09 mm⁻¹
c = 28.628 (3) Å	T = 103 K
V = 2491.8 (3) Å³	Chunk, colourless
Z = 6	0.42 × 0.22 × 0.18 mm
F(000) = 1020

Data collection top

Bruker APEXII CCD area-detector diffractometer	4935 independent reflections
Radiation source: fine-focus sealed tube	4517 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.034
ϕ and ω scans	θ_max = 30.8°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −11→14
T_min = 0.963, T_max = 0.984	k = −14→14
27842 measured reflections	l = −39→39

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)] = 0.040	H-atom parameters constrained
wR(F²) = 0.101	w = 1/[σ²(F_o²) + (0.0551P)² + 0.4841P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.005
4935 reflections	Δρ_max = 0.38 e Å⁻³
203 parameters	Δρ_min = −0.17 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 2049 Friedel pairs
Primary atom site location: structure-invariant direct methods

Crystal data top

C₁₇H₂₈O₅	Z = 6
M_r = 312.39	Mo Kα radiation
Trigonal, P3₂21	µ = 0.09 mm⁻¹
a = 10.0253 (6) Å	T = 103 K
c = 28.628 (3) Å	0.42 × 0.22 × 0.18 mm
V = 2491.8 (3) Å³

Data collection top

Bruker APEXII CCD area-detector diffractometer	4935 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	4517 reflections with I > 2σ(I)
T_min = 0.963, T_max = 0.984	R_int = 0.034
27842 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.101	H-atom parameters constrained
S = 1.05	Δρ_max = 0.38 e Å⁻³
4935 reflections	Δρ_min = −0.17 e Å⁻³
203 parameters	Absolute structure: Flack (1983), 2049 Friedel pairs

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

	x	y	z	U_iso*/U_eq
O1	0.71973 (10)	0.35233 (10)	−0.03898 (3)	0.01837 (18)
O2	0.57224 (11)	0.39122 (11)	0.01212 (3)	0.01993 (19)
O3	0.47049 (10)	0.15908 (12)	−0.05520 (3)	0.0219 (2)
O4	0.45576 (11)	0.06611 (11)	−0.01350 (3)	0.02042 (19)
O5	0.60247 (12)	0.45429 (11)	0.09195 (3)	0.02137 (19)
C1	0.58206 (14)	0.15089 (14)	0.01942 (4)	0.0169 (2)
C2	0.50124 (14)	0.12064 (15)	0.06716 (4)	0.0182 (2)
H2A	0.4266	0.0075	0.0686	0.022*
C3	0.61370 (16)	0.15728 (16)	0.10811 (4)	0.0222 (3)
H3A	0.6848	0.2699	0.1097	0.027*
H3B	0.5550	0.1246	0.1377	0.027*
C4	0.70709 (16)	0.07586 (16)	0.10279 (4)	0.0232 (3)
H4A	0.7788	0.1028	0.1295	0.028*
H4B	0.6367	−0.0370	0.1031	0.028*
C5	0.79822 (16)	0.12223 (15)	0.05735 (4)	0.0213 (2)
H5A	0.8658	0.2368	0.0574	0.026*
C6	0.68604 (15)	0.07809 (14)	0.01577 (4)	0.0185 (2)
H6A	0.6163	−0.0360	0.0174	0.022*
C7	0.77196 (15)	0.11190 (16)	−0.03110 (4)	0.0221 (3)
H7A	0.8677	0.2129	−0.0287	0.027*
H7B	0.8024	0.0330	−0.0361	0.027*
C8	0.68289 (16)	0.11487 (16)	−0.07417 (4)	0.0235 (3)
H8A	0.5935	0.0104	−0.0791	0.028*
H8B	0.7505	0.1408	−0.1019	0.028*
C9	0.62470 (15)	0.23007 (15)	−0.07075 (4)	0.0204 (2)
C10	0.66650 (14)	0.32307 (14)	0.00757 (4)	0.0162 (2)
H10A	0.7569	0.3776	0.0290	0.019*
C11	0.49721 (16)	0.37047 (16)	0.05576 (4)	0.0204 (3)
H11A	0.4239	0.4102	0.0527	0.024*
C12	0.40444 (15)	0.20099 (16)	0.06911 (4)	0.0204 (2)
H12A	0.3232	0.1506	0.0446	0.024*
C13	0.90173 (19)	0.05086 (19)	0.05316 (6)	0.0329 (3)
H13A	0.9584	0.0664	0.0824	0.049*
H13B	0.9748	0.1002	0.0275	0.049*
H13C	0.8382	−0.0597	0.0469	0.049*
C14	0.62461 (17)	0.30416 (18)	−0.11675 (4)	0.0270 (3)
H14A	0.5651	0.3570	−0.1135	0.040*
H14B	0.5779	0.2247	−0.1409	0.040*
H14C	0.7308	0.3788	−0.1256	0.040*
C15	0.68313 (17)	0.61729 (15)	0.08415 (5)	0.0241 (3)
H15A	0.6102	0.6513	0.0743	0.029*
H15B	0.7612	0.6446	0.0593	0.029*
C16	0.7603 (2)	0.69468 (18)	0.12949 (5)	0.0367 (4)
H16A	0.8216	0.8063	0.1247	0.055*
H16B	0.8277	0.6557	0.1398	0.055*
H16C	0.6817	0.6722	0.1533	0.055*
C17	0.31881 (17)	0.17746 (18)	0.11531 (5)	0.0279 (3)
H17A	0.2512	0.2216	0.1130	0.042*
H17B	0.3935	0.2286	0.1405	0.042*
H17C	0.2569	0.0670	0.1220	0.042*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0161 (4)	0.0163 (4)	0.0141 (4)	0.0017 (3)	0.0008 (3)	−0.0006 (3)
O2	0.0224 (5)	0.0212 (4)	0.0165 (4)	0.0111 (4)	0.0022 (3)	0.0025 (3)
O3	0.0158 (4)	0.0247 (5)	0.0149 (4)	0.0025 (4)	−0.0014 (3)	0.0020 (3)
O4	0.0157 (4)	0.0187 (4)	0.0149 (4)	−0.0004 (3)	−0.0015 (3)	0.0003 (3)
O5	0.0256 (5)	0.0165 (4)	0.0181 (4)	0.0076 (4)	−0.0010 (4)	−0.0004 (3)
C1	0.0143 (5)	0.0152 (5)	0.0134 (5)	0.0015 (4)	−0.0007 (4)	−0.0012 (4)
C2	0.0159 (5)	0.0161 (5)	0.0150 (5)	0.0024 (5)	0.0003 (4)	0.0006 (4)
C3	0.0255 (6)	0.0191 (6)	0.0163 (5)	0.0068 (5)	−0.0032 (5)	0.0007 (4)
C4	0.0220 (6)	0.0184 (6)	0.0217 (6)	0.0046 (5)	−0.0041 (5)	0.0046 (5)
C5	0.0181 (6)	0.0150 (5)	0.0260 (6)	0.0045 (5)	−0.0020 (5)	0.0039 (5)
C6	0.0168 (6)	0.0124 (5)	0.0208 (5)	0.0031 (4)	0.0015 (4)	0.0007 (4)
C7	0.0187 (6)	0.0177 (6)	0.0246 (6)	0.0052 (5)	0.0040 (5)	−0.0009 (5)
C8	0.0209 (6)	0.0209 (6)	0.0200 (6)	0.0040 (5)	0.0019 (5)	−0.0044 (5)
C9	0.0167 (6)	0.0201 (6)	0.0145 (5)	0.0019 (5)	0.0004 (4)	−0.0014 (4)
C10	0.0158 (5)	0.0142 (5)	0.0142 (5)	0.0041 (4)	−0.0009 (4)	0.0001 (4)
C11	0.0202 (6)	0.0210 (6)	0.0171 (5)	0.0083 (5)	−0.0007 (4)	−0.0009 (4)
C12	0.0175 (5)	0.0218 (6)	0.0164 (5)	0.0058 (5)	0.0007 (4)	−0.0004 (5)
C13	0.0279 (8)	0.0321 (8)	0.0408 (8)	0.0166 (7)	0.0010 (6)	0.0085 (6)
C14	0.0254 (7)	0.0309 (7)	0.0147 (5)	0.0066 (6)	−0.0010 (5)	0.0006 (5)
C15	0.0282 (7)	0.0160 (6)	0.0243 (6)	0.0082 (5)	0.0009 (5)	0.0022 (5)
C16	0.0504 (10)	0.0186 (7)	0.0300 (7)	0.0090 (7)	−0.0053 (7)	−0.0018 (6)
C17	0.0240 (7)	0.0294 (7)	0.0229 (6)	0.0079 (6)	0.0055 (5)	−0.0007 (5)

Geometric parameters (Å, º) top

O1—C10	1.4105 (14)	C7—H7A	0.990
O1—C9	1.4386 (15)	C7—H7B	0.990
O2—C11	1.4192 (15)	C8—C9	1.536 (2)
O2—C10	1.4221 (15)	C8—H8A	0.990
O3—C9	1.4122 (16)	C8—H8B	0.990
O3—O4	1.4759 (13)	C9—C14	1.5122 (17)
O4—C1	1.4619 (14)	C10—H10A	1.000
O5—C11	1.4163 (15)	C11—C12	1.5224 (18)
O5—C15	1.4327 (16)	C11—H11A	1.000
C1—C10	1.5330 (16)	C12—C17	1.5295 (17)
C1—C2	1.5399 (16)	C12—H12A	1.000
C1—C6	1.5462 (18)	C13—H13A	0.980
C2—C3	1.5382 (17)	C13—H13B	0.980
C2—C12	1.5412 (19)	C13—H13C	0.980
C2—H2A	1.000	C14—H14A	0.980
C3—C4	1.526 (2)	C14—H14B	0.980
C3—H3A	0.990	C14—H14C	0.980
C3—H3B	0.990	C15—C16	1.512 (2)
C4—C5	1.5225 (18)	C15—H15A	0.990
C4—H4A	0.990	C15—H15B	0.990
C4—H4B	0.990	C16—H16A	0.980
C5—C13	1.532 (2)	C16—H16B	0.980
C5—C6	1.5427 (18)	C16—H16C	0.980
C5—H5A	1.000	C17—H17A	0.980
C6—C7	1.5380 (17)	C17—H17B	0.980
C6—H6A	1.000	C17—H17C	0.980
C7—C8	1.5315 (19)

C10—O1—C9	113.55 (9)	O3—C9—C14	104.63 (11)
C11—O2—C10	116.17 (9)	O1—C9—C14	107.15 (11)
C9—O3—O4	108.17 (9)	O3—C9—C8	111.90 (11)
C1—O4—O3	111.72 (8)	O1—C9—C8	110.02 (10)
C11—O5—C15	113.02 (10)	C14—C9—C8	114.05 (11)
O4—C1—C10	110.01 (10)	O1—C10—O2	105.06 (9)
O4—C1—C2	103.89 (9)	O1—C10—C1	112.44 (9)
C10—C1—C2	110.98 (10)	O2—C10—C1	113.28 (10)
O4—C1—C6	105.93 (9)	O1—C10—H10A	108.6
C10—C1—C6	113.17 (10)	O2—C10—H10A	108.6
C2—C1—C6	112.30 (10)	C1—C10—H10A	108.6
C3—C2—C1	112.25 (10)	O5—C11—O2	111.96 (11)
C3—C2—C12	115.18 (10)	O5—C11—C12	109.68 (10)
C1—C2—C12	109.64 (10)	O2—C11—C12	111.59 (11)
C3—C2—H2A	106.4	O5—C11—H11A	107.8
C1—C2—H2A	106.4	O2—C11—H11A	107.8
C12—C2—H2A	106.4	C12—C11—H11A	107.8
C4—C3—C2	111.63 (11)	C11—C12—C17	111.82 (12)
C4—C3—H3A	109.3	C11—C12—C2	112.41 (10)
C2—C3—H3A	109.3	C17—C12—C2	113.72 (11)
C4—C3—H3B	109.3	C11—C12—H12A	106.1
C2—C3—H3B	109.3	C17—C12—H12A	106.1
H3A—C3—H3B	108.0	C2—C12—H12A	106.1
C5—C4—C3	110.91 (11)	C5—C13—H13A	109.5
C5—C4—H4A	109.5	C5—C13—H13B	109.5
C3—C4—H4A	109.5	H13A—C13—H13B	109.5
C5—C4—H4B	109.5	C5—C13—H13C	109.5
C3—C4—H4B	109.5	H13A—C13—H13C	109.5
H4A—C4—H4B	108.0	H13B—C13—H13C	109.5
C4—C5—C13	111.57 (11)	C9—C14—H14A	109.5
C4—C5—C6	109.36 (11)	C9—C14—H14B	109.5
C13—C5—C6	111.87 (12)	H14A—C14—H14B	109.5
C4—C5—H5A	108.0	C9—C14—H14C	109.5
C13—C5—H5A	108.0	H14A—C14—H14C	109.5
C6—C5—H5A	108.0	H14B—C14—H14C	109.5
C7—C6—C5	111.24 (11)	O5—C15—C16	107.69 (11)
C7—C6—C1	112.97 (10)	O5—C15—H15A	110.2
C5—C6—C1	112.30 (10)	C16—C15—H15A	110.2
C7—C6—H6A	106.6	O5—C15—H15B	110.2
C5—C6—H6A	106.6	C16—C15—H15B	110.2
C1—C6—H6A	106.6	H15A—C15—H15B	108.5
C8—C7—C6	116.04 (11)	C15—C16—H16A	109.5
C8—C7—H7A	108.3	C15—C16—H16B	109.5
C6—C7—H7A	108.3	H16A—C16—H16B	109.5
C8—C7—H7B	108.3	C15—C16—H16C	109.5
C6—C7—H7B	108.3	H16A—C16—H16C	109.5
H7A—C7—H7B	107.4	H16B—C16—H16C	109.5
C7—C8—C9	114.06 (11)	C12—C17—H17A	109.5
C7—C8—H8A	108.7	C12—C17—H17B	109.5
C9—C8—H8A	108.7	H17A—C17—H17B	109.5
C7—C8—H8B	108.7	C12—C17—H17C	109.5
C9—C8—H8B	108.7	H17A—C17—H17C	109.5
H8A—C8—H8B	107.6	H17B—C17—H17C	109.5
O3—C9—O1	108.78 (10)

C9—O3—O4—C1	45.64 (12)	O4—O3—C9—C8	48.52 (12)
O3—O4—C1—C10	15.48 (13)	C10—O1—C9—O3	31.99 (14)
O3—O4—C1—C2	134.33 (10)	C10—O1—C9—C14	144.59 (11)
O3—O4—C1—C6	−107.17 (10)	C10—O1—C9—C8	−90.91 (12)
O4—C1—C2—C3	162.62 (10)	C7—C8—C9—O3	−95.86 (13)
C10—C1—C2—C3	−79.19 (13)	C7—C8—C9—O1	25.20 (14)
C6—C1—C2—C3	48.60 (14)	C7—C8—C9—C14	145.62 (12)
O4—C1—C2—C12	−68.02 (12)	C9—O1—C10—O2	−93.06 (11)
C10—C1—C2—C12	50.16 (12)	C9—O1—C10—C1	30.57 (14)
C6—C1—C2—C12	177.96 (10)	C11—O2—C10—O1	176.80 (9)
C1—C2—C3—C4	−52.31 (14)	C11—O2—C10—C1	53.70 (13)
C12—C2—C3—C4	−178.73 (10)	O4—C1—C10—O1	−55.59 (13)
C2—C3—C4—C5	58.53 (14)	C2—C1—C10—O1	−170.00 (10)
C3—C4—C5—C13	175.80 (11)	C6—C1—C10—O1	62.68 (12)
C3—C4—C5—C6	−59.90 (14)	O4—C1—C10—O2	63.33 (12)
C4—C5—C6—C7	−175.83 (11)	C2—C1—C10—O2	−51.08 (12)
C13—C5—C6—C7	−51.70 (14)	C6—C1—C10—O2	−178.40 (9)
C4—C5—C6—C1	56.44 (13)	C15—O5—C11—O2	61.59 (14)
C13—C5—C6—C1	−179.43 (10)	C15—O5—C11—C12	−173.97 (11)
O4—C1—C6—C7	69.20 (12)	C10—O2—C11—O5	69.63 (13)
C10—C1—C6—C7	−51.41 (13)	C10—O2—C11—C12	−53.74 (14)
C2—C1—C6—C7	−178.04 (10)	O5—C11—C12—C17	57.32 (15)
O4—C1—C6—C5	−163.99 (9)	O2—C11—C12—C17	−178.03 (11)
C10—C1—C6—C5	75.39 (12)	O5—C11—C12—C2	−72.01 (13)
C2—C1—C6—C5	−51.23 (13)	O2—C11—C12—C2	52.64 (14)
C5—C6—C7—C8	−164.04 (11)	C3—C2—C12—C11	75.94 (13)
C1—C6—C7—C8	−36.68 (15)	C1—C2—C12—C11	−51.80 (13)
C6—C7—C8—C9	56.69 (15)	C3—C2—C12—C17	−52.41 (15)
O4—O3—C9—O1	−73.25 (12)	C1—C2—C12—C17	179.85 (10)
O4—O3—C9—C14	172.50 (10)	C11—O5—C15—C16	166.33 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O4ⁱ	1.00	2.45	3.3150 (15)	144
C7—H7A···O4ⁱ	0.99	2.55	3.4704 (16)	155

Symmetry code: (i) y+1, x, −z.

Experimental details

Crystal data
Chemical formula	C₁₇H₂₈O₅
M_r	312.39
Crystal system, space group	Trigonal, P3₂21
Temperature (K)	103
a, c (Å)	10.0253 (6), 28.628 (3)
V (Å³)	2491.8 (3)
Z	6
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.42 × 0.22 × 0.18

Data collection
Diffractometer	Bruker APEXII CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.963, 0.984
No. of measured, independent and observed [I > 2σ(I)] reflections	27842, 4935, 4517
R_int	0.034
(sin θ/λ)_max (Å⁻¹)	0.719

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.101, 1.05
No. of reflections	4935
No. of parameters	203
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.17
Absolute structure	Flack (1983), 2049 Friedel pairs

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SHELXS90 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O4ⁱ	1.00	2.45	3.3150 (15)	144
C7—H7A···O4ⁱ	0.99	2.55	3.4704 (16)	155

Symmetry code: (i) y+1, x, −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.

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