5-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-Trimethyl­perhydro-3,12-ep­oxy-1,2-dioxepino[4,3-i]isochromen-10-yl]oxymeth­yl}benzene-1,3-diol

Gul, W.; Carvalho, P.; Galal, A.; Avery, M.A.; El Sohly, M.A.

doi:10.1107/S1600536809002050

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 2| February 2009| Pages o358-o359

doi:10.1107/S1600536809002050

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5-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-Trimethylperhydro-3,12-epoxy-1,2-dioxepino[4,3-i]isochromen-10-yl]oxymethyl}benzene-1,3-diol

Waseem Gul,^a Paulo Carvalho,^b Ahmed Galal,^c Mitchell A. Avery ^b,^c,^d and Mahmoud A. El Sohly ^a,^c ^*

^aEl Sohly Laboratories, Inc, 5 Industrial Park Drive, Oxford, MS 38655, USA, ^bDepartment of Medicinal Chemistry, University of Mississippi, 417 Faser Hall, University, MS 38677, USA, ^cNational Center for Natural Products Research, Department of Pharmaceutics, School of Pharmacy, University of Mississippi, University, MS 38677, USA, and ^dDepartment of Chemistry and Biochemistry, University of Mississippi, University, MS 38677, USA
^*Correspondence e-mail: elsohly@elsohly.com

(Received 15 December 2008; accepted 15 January 2009; online 23 January 2009)

The title compound, C₂₂H₃₀O₇, is a fused five-ring system that is of interest for its anticancer and antimalarial activity. The six-membered C₆ and C₅O rings display chair conformations. The six-membered C₃O₃ ring containing the ether and peroxy functionalities has a distorted boat conformation, with a C—O—O—C torsion angle of 42.6 (1)° for the peroxy group. The seven-membered C₆O ring has a distorted boat-type conformation, while the seven-membered C₅O₂ ring has a very distorted chair-type conformation. The structure contains intermolecular O—H⋯O and O—H⋯(O,O) bonds that link the molecules into sheets parallel to the (100) planes.

Related literature

For the crystallographic analysis of artemisinin, see: Lisgarten et al. (1998 ). For antimalarial and antitumor activity of artemisinin, see Beekman et al. (1997 , 1998 ); Pu et al. (1995 ); Zheng (1994 ).

Experimental

Crystal data

C₂₂H₃₀O₇
M_r = 406.46
Monoclinic, P 2₁
a = 10.3088 (2) Å
b = 10.2844 (2) Å
c = 10.3218 (3) Å
β = 113.14 (1)°
V = 1006.29 (9) Å³
Z = 2
Cu Kα radiation
μ = 0.82 mm⁻¹
T = 100 (2) K
0.23 × 0.15 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: none
15943 measured reflections
3623 independent reflections
3604 reflections with I > 2σ(I)
R_int = 0.019

Refinement

R[F² > 2σ(F²)] = 0.026
wR(F²) = 0.069
S = 1.08
3623 reflections
267 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ), 1623 Friedel pairs
Flack parameter: 0.04 (10)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O6—H6⋯O7ⁱ	0.82	1.99	2.7279 (14)	150
O7—H7⋯O2ⁱⁱ	0.82	2.18	2.8409 (13)	138
O7—H7⋯O4ⁱⁱ	0.82	2.22	2.9269 (13)	144
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+2]$ ; (ii) $[-x+1, y+{\script{1\over 2}}, -z+1]$ .

Data collection: APEX2 (Bruker, 2005 ); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT; 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: ORTEP-3 for Windows (Farrugia, 1997 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809002050/bi2336sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809002050/bi2336Isup2.hkl

checkCIF report

Comment top

The title compound, a new dihydroartemisinin acetal monomeric derivative, has been prepared by reacting dihydroartemisinin with 1,3-dihydroxy-5-hydroxymethyl benzene using BF₃.Et₂O as the coupling catalyst. The compound exhibits anti-malarial, anti-cancer, and antiinfective activity.

Related literature top

For the crystallographic analysis of artemisinin, see: Lisgarten et al. (1998). For the compound's antimalarial and antitumoral activity, see Beekman et al. (1997, 1998); Pu et al. (1995); Zheng (1994).

Experimental top

To a stirred solution of dihydroartemisinin (120 mg, 0.42 mmol) in dry ether (40 ml) was added dry 3,5-dihydroxybenzyl alcohol (28 mg), followed by BF₃.OEt₂ (32 ml). Stirring was continued for two and half hours, after which time the reaction was quenched by addition of 10 ml of 2% aqueous solution of NaHCO₃. The reaction mixture was then diluted with ether (50 ml), and transferred to a separatory funnel and extracted with ether (3 × 30 ml). The ether fractions were pooled, washed with water, and dried over Na₂SO₄. Removal of ether under reduced pressure left an oily crude product, which was purified over Si gel column using a gradient of EtOAc in hexanes (15% to 26%) to yield a colorless solid (35 mg, 28%).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 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: ORTEP-3 for Windows (Farrugia, 1997).

Figures top

Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level for non-H atoms.

5-{[(3R,5aS,6R,8aS,9R,10S,12R, 12aR)-3,6,9-Trimethylperhydro-3,12-epoxy-1,2-dioxepino[4,3- i]isochromen-10-yl]oxymethyl}benzene-1,3-diol top

Crystal data top

C₂₂H₃₀O₇	F(000) = 436
M_r = 406.46	D_x = 1.341 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2yb	Cell parameters from 9920 reflections
a = 10.3088 (2) Å	θ = 4.3–68.9°
b = 10.2844 (2) Å	µ = 0.82 mm⁻¹
c = 10.3218 (3) Å	T = 100 K
β = 113.14 (1)°	Plate, colourless
V = 1006.29 (9) Å³	0.23 × 0.15 × 0.08 mm
Z = 2

Data collection top

Bruker APEXII CCD diffractometer	3604 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube, Siemens KFF Cu 2 K90	R_int = 0.019
Graphite monochromator	θ_max = 69.3°, θ_min = 4.7°
ϕ and ω scans	h = −12→12
15943 measured reflections	k = −11→12
3623 independent reflections	l = −12→12

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)] = 0.026	H-atom parameters constrained
wR(F²) = 0.069	w = 1/[σ²(F_o²) + (0.0416P)² + 0.199P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
3623 reflections	Δρ_max = 0.25 e Å⁻³
267 parameters	Δρ_min = −0.22 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 1623 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.04 (10)

Crystal data top

C₂₂H₃₀O₇	V = 1006.29 (9) Å³
M_r = 406.46	Z = 2
Monoclinic, P2₁	Cu Kα radiation
a = 10.3088 (2) Å	µ = 0.82 mm⁻¹
b = 10.2844 (2) Å	T = 100 K
c = 10.3218 (3) Å	0.23 × 0.15 × 0.08 mm
β = 113.14 (1)°

Data collection top

Bruker APEXII CCD diffractometer	3604 reflections with I > 2σ(I)
15943 measured reflections	R_int = 0.019
3623 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.026	H-atom parameters constrained
wR(F²) = 0.069	Δρ_max = 0.25 e Å⁻³
S = 1.08	Δρ_min = −0.22 e Å⁻³
3623 reflections	Absolute structure: Flack (1983), 1623 Friedel pairs
267 parameters	Absolute structure parameter: 0.04 (10)
1 restraint

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
O4	0.24620 (9)	0.53498 (9)	0.32197 (9)	0.01671 (19)
O1	−0.02356 (10)	0.56559 (9)	0.09293 (9)	0.0177 (2)
O6	0.41598 (11)	0.67491 (10)	1.04175 (10)	0.0238 (2)
H6	0.3735	0.6057	1.0194	0.036*
O5	0.34731 (9)	0.70855 (9)	0.47383 (9)	0.01720 (19)
O3	0.07779 (9)	0.40591 (9)	0.33999 (9)	0.0184 (2)
O7	0.71639 (10)	0.95263 (9)	0.93260 (10)	0.0213 (2)
H7	0.7608	0.9578	0.8820	0.032*
O2	0.02421 (10)	0.42912 (9)	0.10142 (9)	0.0191 (2)
C18	0.58553 (13)	0.79300 (13)	0.75672 (13)	0.0177 (3)
H18	0.6249	0.8215	0.6946	0.021*
C1	−0.01197 (14)	0.36064 (14)	0.20186 (14)	0.0204 (3)
C20	0.56095 (14)	0.81251 (13)	0.97930 (13)	0.0178 (3)
H20	0.5828	0.8554	1.0646	0.021*
C10	0.31061 (13)	0.66001 (13)	0.33627 (13)	0.0172 (3)
H10	0.3973	0.6505	0.3195	0.021*
C8	0.06357 (14)	0.75832 (13)	0.22778 (13)	0.0166 (3)
H8	0.0018	0.7965	0.1376	0.020*
C4	−0.13890 (13)	0.62313 (15)	0.24865 (13)	0.0193 (3)
H4	−0.2079	0.6579	0.1599	0.023*
C11	0.11686 (13)	0.53590 (13)	0.34304 (13)	0.0158 (3)
H11	0.1353	0.5713	0.4368	0.019*
C12	0.00544 (13)	0.62013 (13)	0.23280 (13)	0.0161 (3)
C22	0.43232 (13)	0.64640 (13)	0.81424 (14)	0.0184 (3)
H22	0.3703	0.5763	0.7905	0.022*
C7	0.05456 (14)	0.84730 (14)	0.34327 (14)	0.0198 (3)
H7A	0.1191	0.8161	0.4346	0.024*
H7B	0.0834	0.9345	0.3305	0.024*
C5	−0.13896 (13)	0.71641 (15)	0.36552 (13)	0.0221 (3)
H5	−0.0685	0.6848	0.4551	0.026*
C15	0.28159 (15)	0.88607 (14)	0.23539 (15)	0.0233 (3)
H15A	0.3043	0.9221	0.3276	0.035*
H15B	0.2171	0.9428	0.1660	0.035*
H15C	0.3662	0.8771	0.2183	0.035*
C14	−0.28261 (14)	0.71858 (18)	0.37886 (15)	0.0297 (3)
H14A	−0.2827	0.7861	0.4430	0.044*
H14B	−0.2986	0.6362	0.4137	0.044*
H14C	−0.3561	0.7348	0.2881	0.044*
C17	0.48996 (13)	0.69005 (13)	0.72052 (13)	0.0174 (3)
C6	−0.09417 (15)	0.85158 (15)	0.34012 (14)	0.0231 (3)
H6A	−0.0971	0.9106	0.4123	0.028*
H6B	−0.1590	0.8836	0.2493	0.028*
C16	0.44908 (14)	0.62693 (14)	0.57838 (14)	0.0200 (3)
H16A	0.5318	0.6160	0.5566	0.024*
H16B	0.4087	0.5418	0.5788	0.024*
C9	0.21337 (13)	0.75281 (13)	0.22646 (13)	0.0178 (3)
H9	0.2017	0.7167	0.1347	0.021*
C21	0.46825 (13)	0.70848 (14)	0.94374 (13)	0.0186 (3)
C19	0.62111 (13)	0.85242 (13)	0.88701 (14)	0.0173 (3)
C3	−0.19196 (14)	0.48755 (15)	0.26635 (14)	0.0237 (3)
H3A	−0.1469	0.4632	0.3649	0.028*
H3B	−0.2925	0.4932	0.2432	0.028*
C2	−0.16688 (14)	0.37942 (15)	0.17856 (14)	0.0234 (3)
H2A	−0.2207	0.3982	0.0797	0.028*
H2B	−0.2024	0.2986	0.2004	0.028*
C13	0.02745 (16)	0.22097 (15)	0.19089 (15)	0.0262 (3)
H13A	−0.0393	0.1835	0.1055	0.039*
H13B	0.0267	0.1729	0.2703	0.039*
H13C	0.1201	0.2176	0.1899	0.039*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0160 (4)	0.0163 (5)	0.0179 (4)	−0.0009 (3)	0.0068 (4)	−0.0024 (3)
O1	0.0225 (5)	0.0173 (5)	0.0130 (4)	−0.0007 (4)	0.0067 (4)	−0.0007 (4)
O6	0.0285 (5)	0.0254 (5)	0.0221 (5)	−0.0052 (4)	0.0149 (4)	0.0005 (4)
O5	0.0169 (4)	0.0187 (5)	0.0140 (4)	0.0006 (4)	0.0039 (3)	−0.0015 (3)
O3	0.0215 (5)	0.0181 (5)	0.0140 (4)	−0.0030 (4)	0.0051 (4)	−0.0005 (3)
O7	0.0232 (5)	0.0217 (5)	0.0232 (5)	−0.0058 (4)	0.0138 (4)	−0.0047 (4)
O2	0.0234 (5)	0.0183 (5)	0.0170 (4)	−0.0016 (4)	0.0094 (4)	−0.0024 (4)
C18	0.0191 (6)	0.0192 (7)	0.0165 (6)	0.0030 (5)	0.0088 (5)	0.0022 (5)
C1	0.0246 (7)	0.0215 (7)	0.0146 (6)	−0.0075 (5)	0.0072 (5)	−0.0028 (5)
C20	0.0185 (6)	0.0203 (7)	0.0145 (6)	0.0029 (5)	0.0063 (5)	−0.0002 (5)
C10	0.0165 (6)	0.0197 (7)	0.0162 (6)	−0.0034 (5)	0.0074 (5)	−0.0032 (5)
C8	0.0192 (6)	0.0167 (7)	0.0134 (6)	0.0021 (5)	0.0060 (5)	0.0014 (5)
C4	0.0149 (6)	0.0279 (7)	0.0146 (6)	0.0008 (5)	0.0052 (5)	0.0002 (5)
C11	0.0177 (6)	0.0158 (7)	0.0149 (6)	−0.0018 (5)	0.0075 (5)	−0.0022 (5)
C12	0.0176 (6)	0.0202 (7)	0.0109 (6)	−0.0015 (5)	0.0060 (5)	−0.0016 (5)
C22	0.0147 (6)	0.0170 (7)	0.0220 (6)	−0.0001 (5)	0.0055 (5)	0.0005 (5)
C7	0.0229 (7)	0.0170 (7)	0.0185 (6)	0.0017 (5)	0.0072 (5)	−0.0011 (5)
C5	0.0178 (6)	0.0329 (8)	0.0153 (6)	0.0039 (6)	0.0063 (5)	0.0005 (6)
C15	0.0253 (7)	0.0239 (8)	0.0213 (7)	−0.0053 (6)	0.0097 (6)	−0.0003 (6)
C14	0.0222 (7)	0.0464 (10)	0.0225 (7)	0.0053 (7)	0.0112 (6)	−0.0023 (7)
C17	0.0150 (5)	0.0182 (7)	0.0174 (6)	0.0050 (5)	0.0045 (5)	0.0015 (5)
C6	0.0249 (7)	0.0269 (8)	0.0177 (6)	0.0080 (6)	0.0086 (5)	−0.0015 (6)
C16	0.0190 (6)	0.0200 (7)	0.0190 (6)	0.0032 (5)	0.0053 (5)	0.0005 (5)
C9	0.0195 (6)	0.0209 (7)	0.0139 (6)	−0.0036 (5)	0.0075 (5)	−0.0016 (5)
C21	0.0159 (6)	0.0215 (7)	0.0189 (6)	0.0038 (5)	0.0075 (5)	0.0044 (5)
C19	0.0147 (6)	0.0164 (7)	0.0199 (6)	0.0019 (5)	0.0058 (5)	0.0023 (5)
C3	0.0178 (6)	0.0346 (8)	0.0196 (6)	−0.0045 (6)	0.0082 (5)	0.0006 (6)
C2	0.0227 (7)	0.0279 (8)	0.0190 (6)	−0.0101 (6)	0.0075 (5)	−0.0011 (5)
C13	0.0335 (7)	0.0225 (8)	0.0213 (7)	−0.0056 (6)	0.0094 (6)	−0.0031 (6)

Geometric parameters (Å, º) top

O4—C10	1.4280 (16)	C11—H11	0.980
O4—C11	1.4328 (15)	C22—C17	1.3936 (19)
O1—C12	1.4660 (15)	C22—C21	1.3937 (19)
O1—O2	1.4785 (13)	C22—H22	0.930
O6—C21	1.3644 (16)	C7—C6	1.5214 (19)
O6—H6	0.820	C7—H7A	0.970
O5—C10	1.4092 (15)	C7—H7B	0.970
O5—C16	1.4423 (16)	C5—C6	1.520 (2)
O3—C11	1.3930 (17)	C5—C14	1.5403 (17)
O3—C1	1.4384 (15)	C5—H5	0.980
O7—C19	1.3730 (16)	C15—C9	1.5266 (19)
O7—H7	0.820	C15—H15A	0.960
O2—C1	1.4191 (16)	C15—H15B	0.960
C18—C19	1.3888 (18)	C15—H15C	0.960
C18—C17	1.3936 (19)	C14—H14A	0.960
C18—H18	0.930	C14—H14B	0.960
C1—C13	1.509 (2)	C14—H14C	0.960
C1—C2	1.5308 (19)	C17—C16	1.5052 (18)
C20—C21	1.3845 (19)	C6—H6A	0.970
C20—C19	1.3874 (18)	C6—H6B	0.970
C20—H20	0.930	C16—H16A	0.970
C10—C9	1.5190 (18)	C16—H16B	0.970
C10—H10	0.980	C9—H9	0.980
C8—C7	1.5344 (18)	C3—C2	1.520 (2)
C8—C9	1.5506 (17)	C3—H3A	0.970
C8—C12	1.5512 (18)	C3—H3B	0.970
C8—H8	0.980	C2—H2A	0.970
C4—C3	1.535 (2)	C2—H2B	0.970
C4—C5	1.5415 (19)	C13—H13A	0.960
C4—C12	1.5598 (16)	C13—H13B	0.960
C4—H4	0.980	C13—H13C	0.960
C11—C12	1.5289 (17)

C10—O4—C11	113.64 (9)	C6—C5—H5	107.7
C12—O1—O2	111.75 (9)	C14—C5—H5	107.7
C21—O6—H6	109.5	C4—C5—H5	107.7
C10—O5—C16	112.09 (10)	C9—C15—H15A	109.5
C11—O3—C1	113.63 (10)	C9—C15—H15B	109.5
C19—O7—H7	109.5	H15A—C15—H15B	109.5
C1—O2—O1	109.72 (9)	C9—C15—H15C	109.5
C19—C18—C17	118.94 (12)	H15A—C15—H15C	109.5
C19—C18—H18	120.5	H15B—C15—H15C	109.5
C17—C18—H18	120.5	C5—C14—H14A	109.5
O2—C1—O3	108.18 (10)	C5—C14—H14B	109.5
O2—C1—C13	105.17 (11)	H14A—C14—H14B	109.5
O3—C1—C13	107.17 (11)	C5—C14—H14C	109.5
O2—C1—C2	112.33 (11)	H14A—C14—H14C	109.5
O3—C1—C2	109.88 (10)	H14B—C14—H14C	109.5
C13—C1—C2	113.79 (11)	C22—C17—C18	120.53 (12)
C21—C20—C19	119.65 (12)	C22—C17—C16	120.35 (12)
C21—C20—H20	120.2	C18—C17—C16	119.12 (12)
C19—C20—H20	120.2	C5—C6—C7	109.99 (11)
O5—C10—O4	110.67 (10)	C5—C6—H6A	109.7
O5—C10—C9	111.50 (10)	C7—C6—H6A	109.7
O4—C10—C9	110.18 (10)	C5—C6—H6B	109.7
O5—C10—H10	108.1	C7—C6—H6B	109.7
O4—C10—H10	108.1	H6A—C6—H6B	108.2
C9—C10—H10	108.1	O5—C16—C17	108.73 (10)
C7—C8—C9	113.15 (11)	O5—C16—H16A	109.9
C7—C8—C12	112.23 (10)	C17—C16—H16A	109.9
C9—C8—C12	111.46 (10)	O5—C16—H16B	109.9
C7—C8—H8	106.5	C17—C16—H16B	109.9
C9—C8—H8	106.5	H16A—C16—H16B	108.3
C12—C8—H8	106.5	C10—C9—C15	111.45 (11)
C3—C4—C5	111.25 (11)	C10—C9—C8	112.57 (10)
C3—C4—C12	113.19 (11)	C15—C9—C8	113.79 (11)
C5—C4—C12	112.84 (10)	C10—C9—H9	106.1
C3—C4—H4	106.3	C15—C9—H9	106.1
C5—C4—H4	106.3	C8—C9—H9	106.1
C12—C4—H4	106.3	O6—C21—C20	115.57 (12)
O3—C11—O4	105.56 (10)	O6—C21—C22	124.17 (12)
O3—C11—C12	113.63 (10)	C20—C21—C22	120.26 (12)
O4—C11—C12	111.25 (10)	O7—C19—C20	116.06 (11)
O3—C11—H11	108.8	O7—C19—C18	122.91 (11)
O4—C11—H11	108.8	C20—C19—C18	121.03 (12)
C12—C11—H11	108.8	C2—C3—C4	116.22 (11)
O1—C12—C11	108.60 (10)	C2—C3—H3A	108.2
O1—C12—C8	104.45 (9)	C4—C3—H3A	108.2
C11—C12—C8	110.91 (10)	C2—C3—H3B	108.2
O1—C12—C4	106.09 (10)	C4—C3—H3B	108.2
C11—C12—C4	113.69 (10)	H3A—C3—H3B	107.4
C8—C12—C4	112.48 (11)	C3—C2—C1	114.21 (11)
C17—C22—C21	119.54 (12)	C3—C2—H2A	108.7
C17—C22—H22	120.2	C1—C2—H2A	108.7
C21—C22—H22	120.2	C3—C2—H2B	108.7
C6—C7—C8	111.64 (11)	C1—C2—H2B	108.7
C6—C7—H7A	109.3	H2A—C2—H2B	107.6
C8—C7—H7A	109.3	C1—C13—H13A	109.5
C6—C7—H7B	109.3	C1—C13—H13B	109.5
C8—C7—H7B	109.3	H13A—C13—H13B	109.5
H7A—C7—H7B	108.0	C1—C13—H13C	109.5
C6—C5—C14	111.72 (12)	H13A—C13—H13C	109.5
C6—C5—C4	109.92 (11)	H13B—C13—H13C	109.5
C14—C5—C4	112.02 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···O7ⁱ	0.82	1.99	2.7279 (14)	150
O7—H7···O2ⁱⁱ	0.82	2.18	2.8409 (13)	138
O7—H7···O4ⁱⁱ	0.82	2.22	2.9269 (13)	144

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

Experimental details

Crystal data
Chemical formula	C₂₂H₃₀O₇
M_r	406.46
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	100
a, b, c (Å)	10.3088 (2), 10.2844 (2), 10.3218 (3)
β (°)	113.14 (1)
V (Å³)	1006.29 (9)
Z	2
Radiation type	Cu Kα
µ (mm⁻¹)	0.82
Crystal size (mm)	0.23 × 0.15 × 0.08

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	15943, 3623, 3604
R_int	0.019
(sin θ/λ)_max (Å⁻¹)	0.607

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.026, 0.069, 1.08
No. of reflections	3623
No. of parameters	267
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.22
Absolute structure	Flack (1983), 1623 Friedel pairs
Absolute structure parameter	0.04 (10)

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···O7ⁱ	0.82	1.99	2.7279 (14)	150.2
O7—H7···O2ⁱⁱ	0.82	2.18	2.8409 (13)	138.4
O7—H7···O4ⁱⁱ	0.82	2.22	2.9269 (13)	143.8

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

Acknowledgements

The authors thank the Center for Disease Control and Prevention, USA, for providing financial assistance (CDC cooperative agreements 1UO1 CI000211–03 and1UO1 CI000362–01). This Investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant No. C06 Rr-14503–01 from the National Center for Research Resources, National Institutes of Health.

References

Beekman, A. C., Barentsen, A. R. W., Woerdenbag, H. J., Uden, W. V., Pras, N., Konings, A. W. T., El-Feraly, F. S., Galal, A. M. & Wikström, H. V. (1997). J. Nat. Prod. 60, 325–330. CrossRef CAS PubMed Web of Science Google Scholar
Beekman, A. C., Wierenga, P. K., Woerdenbag, H. J., Uden, W. V., Pras, N., Konings, A. W. T., El-Feraly, F. S., Galal, A. M. & Wikström, H. V. (1998). Planta Med. 64, 615–619. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Lisgarten, J. N., Potter, B. S., Bantuzeko, C. & Palmer, R. A. (1998). J. Chem. Crystallogr. 28, 539–543. Web of Science CSD CrossRef CAS Google Scholar
Pu, Y. M., Torok, D. S., Ziffer, H., Pan, X.-Q. & Meshnick, S. R. (1995). J. Med. Chem. 38, 4120–4124. CrossRef CAS PubMed Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Zheng, G. Q. (1994). Planta Med. 60, 54–58. CrossRef CAS PubMed Web of Science Google Scholar

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Volume 65| Part 2| February 2009| Pages o358-o359

doi:10.1107/S1600536809002050

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

5-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-Tri­methyl­perhydro-3,12-ep­­oxy-1,2-dioxepino[4,3-i]isochromen-10-yl]oxymeth­yl}benzene-1,3-diol

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

5-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-Trimethylperhydro-3,12-epoxy-1,2-dioxepino[4,3-i]isochromen-10-yl]oxymethyl}benzene-1,3-diol