5-{[(3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-Trimethyl-perhydro-3,12-ep-oxy-1,2-dioxepino[4,3-i]isochromen-10-yl]oxymeth-yl}benzene-1,3-diol.

The title compound, C(22)H(30)O(7), is a fused five-ring system that is of inter-est for its anti-cancer and anti-malarial activity. The six-membered C(6) and C(5)O rings display chair conformations. The six-membered C(3)O(3) ring containing the ether and per-oxy functionalities has a distorted boat conformation, with a C-O-O-C torsion angle of 42.6 (1)° for the per-oxy group. The seven-membered C(6)O ring has a distorted boat-type conformation, while the seven-membered C(5)O(2) ring has a very distorted chair-type conformation. The structure contains inter-molecular O-H⋯O and O-H⋯(O,O) bonds that link the mol-ecules 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 = 406.46

Monoclinic,

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[F 2 > 2σ(F 2)] = 0.026

wR(F 2) = 0.069

S = 1.08

3623 reflections

267 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.25 e Å−3

Δρmin = −0.22 e Å−3

Absolute structure: Flack (1983 ▶), 1623 Friedel pairs

Flack parameter: 0.04 (10)

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 ▶).

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

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

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

C22H30O7	F(000) = 436
Mr = 406.46	Dx = 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

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

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(Fo2) + (0.0416P)2 + 0.199P] where P = (Fo2 + 2Fc2)/3
S = 1.08	(Δ/σ)max < 0.001
3623 reflections	Δρmax = 0.25 e Å−3
267 parameters	Δρmin = −0.22 e Å−3
1 restraint	Absolute structure: Flack (1983), 1623 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.04 (10)

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.

	x	y	z	Uiso*/Ueq
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*

	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)

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)

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

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) ; (ii) .