1,2-Bis[(3,6,9-trimethyl-3,12-ep-oxy-3,4,5,5a,6,7,8,8a,9,10,12,12a-dodeca-hydro-pyrano[4,3-j][1,2]benzodioxepin-4-yl)-oxy]ethane.

The title compound, C(32)H(50)O(10), prepared from a mixture of α- and β-dihydro-artemisinin, has two β-arteether moieties linked via an -OCH(2)CH(2)O- bridge, so that the mol-ecule is symmetric about the bridge. Each asymmetric unit contains a β-arteether moiety and an -OCH(2) group, which is only one-half of the mol-ecule. The endo-peroxide bridges of the parent compounds have been retained in each half of the diol-bridged dimer. The rings exhibit chair and twist-boat conformations.

Related literature

For related literature and structures, see: Brossi et al. (1988 ▶); Dominguez Gerpe et al. (1988 ▶); Flack & Bernardinelli (2000 ▶); Flippen-Anderson et al. (1989 ▶); Haynes et al. (2002 ▶); Luo et al. (1984 ▶); Paik et al. (2006 ▶); Qinghaosu Research Group (1980 ▶); Venugopalan et al. (1995 ▶); Woerdenbag et al. (1993 ▶); Yue et al. (2006 ▶). For the synthesis, see: Posner et al. (1997 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C32H50O10

M = 594.72

Monoclinic,

a = 18.033 (4) Å

b = 9.3127 (19) Å

c = 11.061 (2) Å

β = 123.58 (3)°

V = 1547.5 (8) Å3

Z = 2

Mo Kα radiation

μ = 0.09 mm−1

T = 295 K

0.42 × 0.38 × 0.31 mm

Data collection

Rigaku R-AXIS RAPID diffractometer

Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T min = 0.962, T max = 0.972

6717 measured reflections

1614 independent reflections

1195 reflections with I > 2σ(I)

R int = 0.043

Refinement

R[F 2 > 2σ(F 2)] = 0.042

wR(F 2) = 0.129

S = 1.10

1614 reflections

194 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.20 e Å−3

Δρmin = −0.20 e Å−3

Data collection: RAPID-AUTO (Rigaku, 1998 ▶); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812005089/jj2118sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812005089/jj2118Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812005089/jj2118Isup3.cml

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

C32H50O10	F(000) = 644
Mr = 594.72	Dx = 1.276 Mg m−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 5507 reflections
a = 18.033 (4) Å	θ = 3.7–26.0°
b = 9.3127 (19) Å	µ = 0.09 mm−1
c = 11.061 (2) Å	T = 295 K
β = 123.58 (3)°	Prism, colorless
V = 1547.5 (8) Å3	0.42 × 0.38 × 0.31 mm
Z = 2

Rigaku R-AXIS RAPID diffractometer	1614 independent reflections
Radiation source: fine-focus sealed tube	1195 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.043
Detector resolution: 10.000 pixels mm-1	θmax = 26.0°, θmin = 3.7°
ω scans	h = −22→22
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −11→9
Tmin = 0.962, Tmax = 0.972	l = −13→13
6717 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.129	H-atom parameters constrained
S = 1.10	w = 1/[σ2(Fo2) + (0.0715P)2 + 0.1671P] where P = (Fo2 + 2Fc2)/3
1614 reflections	(Δ/σ)max < 0.001
194 parameters	Δρmax = 0.20 e Å−3
1 restraint	Δρmin = −0.20 e Å−3

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
O1	0.85534 (15)	0.7920 (3)	0.4203 (3)	0.0696 (7)
O2	0.81128 (13)	0.6711 (3)	0.4401 (2)	0.0638 (7)
O3	0.76331 (14)	0.7918 (3)	0.1695 (2)	0.0578 (6)
O4	0.68018 (14)	0.8818 (2)	0.2453 (3)	0.0600 (6)
O5	0.52997 (15)	0.8430 (3)	0.1553 (3)	0.0655 (7)
C1	0.8536 (2)	0.7701 (5)	0.2924 (4)	0.0638 (9)
C2	0.8844 (2)	0.6212 (5)	0.2839 (5)	0.0741 (11)
H2A	0.9172	0.6284	0.2382	0.089*
H2B	0.9251	0.5858	0.3818	0.089*
C3	0.8104 (2)	0.5128 (4)	0.2012 (5)	0.0694 (10)
H3A	0.8369	0.4211	0.2041	0.083*
H3B	0.7740	0.5427	0.1005	0.083*
C4	0.7496 (2)	0.4904 (4)	0.2559 (4)	0.0590 (8)
H4A	0.7836	0.4307	0.3431	0.071*
C5	0.6668 (2)	0.4016 (4)	0.1475 (4)	0.0652 (9)
H5	0.6336	0.4546	0.0557	0.078*
C6	0.6066 (2)	0.3825 (4)	0.2020 (4)	0.0700 (10)
H6A	0.5535	0.3308	0.1298	0.084*
H6B	0.6371	0.3255	0.2901	0.084*
C7	0.5804 (2)	0.5246 (4)	0.2323 (4)	0.0642 (9)
H7A	0.5408	0.5085	0.2645	0.077*
H7B	0.5485	0.5805	0.1435	0.077*
C8	0.6620 (2)	0.6093 (4)	0.3487 (4)	0.0576 (8)
H8	0.6917	0.5495	0.4362	0.069*
C9	0.6407 (2)	0.7511 (4)	0.3906 (4)	0.0634 (9)
H9	0.6964	0.7825	0.4786	0.076*
C10	0.6163 (2)	0.8677 (4)	0.2800 (4)	0.0643 (9)
H10	0.6147	0.9586	0.3231	0.077*
C11	0.6992 (2)	0.7533 (3)	0.1973 (4)	0.0505 (7)
H11	0.6452	0.7232	0.1059	0.061*
C12	0.72923 (18)	0.6310 (4)	0.3060 (3)	0.0497 (7)
C13	0.9078 (3)	0.8911 (6)	0.2898 (5)	0.0916 (15)
H13A	0.8908	0.9796	0.3125	0.137*
H13B	0.8974	0.8977	0.1950	0.137*
H13C	0.9698	0.8732	0.3603	0.137*
C14	0.6926 (4)	0.2560 (5)	0.1183 (6)	0.0950 (14)
H14A	0.7275	0.2040	0.2078	0.143*
H14B	0.7269	0.2700	0.0768	0.143*
H14C	0.6398	0.2025	0.0520	0.143*
C15	0.5731 (3)	0.7405 (6)	0.4325 (5)	0.0923 (15)
H15A	0.5162	0.7137	0.3490	0.138*
H15B	0.5684	0.8318	0.4680	0.138*
H15C	0.5924	0.6693	0.5070	0.138*
C16	0.4917 (3)	0.9620 (4)	0.0595 (5)	0.0737 (10)
H16A	0.5156	1.0498	0.1152	0.088*
H16B	0.4280	0.9619	0.0162	0.088*

	U11	U22	U33	U12	U13	U23
O1	0.0611 (13)	0.0951 (18)	0.0531 (14)	−0.0343 (13)	0.0319 (11)	−0.0154 (14)
O2	0.0523 (11)	0.0890 (17)	0.0424 (12)	−0.0224 (12)	0.0214 (9)	−0.0031 (12)
O3	0.0544 (11)	0.0700 (15)	0.0532 (13)	−0.0115 (10)	0.0324 (10)	0.0023 (11)
O4	0.0605 (13)	0.0547 (13)	0.0710 (16)	−0.0134 (11)	0.0401 (12)	−0.0100 (12)
O5	0.0583 (12)	0.0607 (14)	0.0762 (17)	−0.0088 (11)	0.0364 (12)	−0.0090 (13)
C1	0.0488 (17)	0.091 (2)	0.0528 (19)	−0.0159 (17)	0.0287 (15)	−0.0025 (19)
C2	0.0547 (19)	0.098 (3)	0.073 (3)	0.002 (2)	0.0372 (18)	0.007 (2)
C3	0.067 (2)	0.078 (3)	0.067 (2)	0.0031 (18)	0.0399 (19)	0.002 (2)
C4	0.0566 (17)	0.061 (2)	0.050 (2)	−0.0021 (15)	0.0237 (15)	0.0081 (16)
C5	0.073 (2)	0.056 (2)	0.055 (2)	−0.0097 (17)	0.0284 (18)	0.0009 (17)
C6	0.073 (2)	0.060 (2)	0.062 (2)	−0.0256 (18)	0.0282 (18)	−0.0002 (19)
C7	0.0589 (18)	0.068 (2)	0.065 (2)	−0.0213 (16)	0.0337 (17)	−0.0048 (18)
C8	0.0548 (17)	0.071 (2)	0.0455 (18)	−0.0178 (15)	0.0267 (15)	−0.0040 (17)
C9	0.0580 (18)	0.086 (2)	0.054 (2)	−0.0178 (17)	0.0354 (16)	−0.0146 (19)
C10	0.0571 (17)	0.068 (2)	0.074 (2)	−0.0143 (17)	0.0399 (17)	−0.020 (2)
C11	0.0509 (17)	0.0509 (17)	0.0500 (18)	−0.0146 (13)	0.0281 (15)	−0.0052 (14)
C12	0.0446 (14)	0.0619 (19)	0.0361 (15)	−0.0144 (13)	0.0183 (12)	−0.0016 (14)
C13	0.073 (2)	0.129 (4)	0.079 (3)	−0.044 (3)	0.046 (2)	−0.013 (3)
C14	0.116 (3)	0.066 (3)	0.100 (4)	−0.009 (2)	0.057 (3)	−0.013 (3)
C15	0.087 (3)	0.129 (4)	0.086 (3)	−0.030 (3)	0.063 (3)	−0.024 (3)
C16	0.071 (2)	0.0533 (19)	0.093 (3)	0.0042 (17)	0.043 (2)	−0.005 (2)

O1—C1	1.412 (4)	C6—H6B	0.9700
O1—O2	1.463 (3)	C7—C8	1.532 (4)
O2—C12	1.450 (3)	C7—H7A	0.9700
O3—C11	1.397 (3)	C7—H7B	0.9700
O3—C1	1.446 (4)	C8—C9	1.518 (5)
O4—C10	1.407 (4)	C8—C12	1.538 (4)
O4—C11	1.426 (4)	C8—H8	0.9800
O5—C10	1.416 (4)	C9—C10	1.508 (5)
O5—C16	1.421 (5)	C9—C15	1.528 (5)
C1—C13	1.502 (5)	C9—H9	0.9800
C1—C2	1.516 (6)	C10—H10	0.9800
C2—C3	1.512 (6)	C11—C12	1.522 (4)
C2—H2A	0.9700	C11—H11	0.9800
C2—H2B	0.9700	C13—H13A	0.9600
C3—C4	1.532 (5)	C13—H13B	0.9600
C3—H3A	0.9700	C13—H13C	0.9600
C3—H3B	0.9700	C14—H14A	0.9600
C4—C5	1.539 (5)	C14—H14B	0.9600
C4—C12	1.544 (5)	C14—H14C	0.9600
C4—H4A	0.9800	C15—H15A	0.9600
C5—C6	1.515 (5)	C15—H15B	0.9600
C5—C14	1.525 (6)	C15—H15C	0.9600
C5—H5	0.9800	C16—C16i	1.504 (9)
C6—C7	1.504 (5)	C16—H16A	0.9700
C6—H6A	0.9700	C16—H16B	0.9700
C1—O1—O2	109.0 (2)	C7—C8—H8	106.5
C12—O2—O1	112.1 (2)	C12—C8—H8	106.5
C11—O3—C1	113.3 (2)	C10—C9—C8	112.8 (3)
C10—O4—C11	115.2 (2)	C10—C9—C15	111.6 (3)
C10—O5—C16	114.8 (3)	C8—C9—C15	114.6 (3)
O1—C1—O3	108.1 (3)	C10—C9—H9	105.6
O1—C1—C13	104.9 (3)	C8—C9—H9	105.6
O3—C1—C13	106.5 (3)	C15—C9—H9	105.6
O1—C1—C2	112.8 (3)	O4—C10—O5	112.0 (3)
O3—C1—C2	109.3 (3)	O4—C10—C9	111.9 (3)
C13—C1—C2	114.8 (3)	O5—C10—C9	110.1 (3)
C3—C2—C1	114.7 (3)	O4—C10—H10	107.6
C3—C2—H2A	108.6	O5—C10—H10	107.6
C1—C2—H2A	108.6	C9—C10—H10	107.6
C3—C2—H2B	108.6	O3—C11—O4	105.4 (2)
C1—C2—H2B	108.6	O3—C11—C12	113.0 (2)
H2A—C2—H2B	107.6	O4—C11—C12	112.8 (2)
C2—C3—C4	115.9 (3)	O3—C11—H11	108.5
C2—C3—H3A	108.3	O4—C11—H11	108.5
C4—C3—H3A	108.3	C12—C11—H11	108.5
C2—C3—H3B	108.3	O2—C12—C11	109.4 (2)
C4—C3—H3B	108.3	O2—C12—C8	104.6 (2)
H3A—C3—H3B	107.4	C11—C12—C8	110.1 (2)
C3—C4—C5	111.3 (3)	O2—C12—C4	106.0 (2)
C3—C4—C12	113.0 (3)	C11—C12—C4	113.7 (2)
C5—C4—C12	114.5 (3)	C8—C12—C4	112.5 (2)
C3—C4—H4A	105.7	C1—C13—H13A	109.5
C5—C4—H4A	105.7	C1—C13—H13B	109.5
C12—C4—H4A	105.7	H13A—C13—H13B	109.5
C6—C5—C14	110.4 (3)	C1—C13—H13C	109.5
C6—C5—C4	110.7 (3)	H13A—C13—H13C	109.5
C14—C5—C4	111.3 (3)	H13B—C13—H13C	109.5
C6—C5—H5	108.1	C5—C14—H14A	109.5
C14—C5—H5	108.1	C5—C14—H14B	109.5
C4—C5—H5	108.1	H14A—C14—H14B	109.5
C7—C6—C5	111.5 (3)	C5—C14—H14C	109.5
C7—C6—H6A	109.3	H14A—C14—H14C	109.5
C5—C6—H6A	109.3	H14B—C14—H14C	109.5
C7—C6—H6B	109.3	C9—C15—H15A	109.5
C5—C6—H6B	109.3	C9—C15—H15B	109.5
H6A—C6—H6B	108.0	H15A—C15—H15B	109.5
C6—C7—C8	111.5 (3)	C9—C15—H15C	109.5
C6—C7—H7A	109.3	H15A—C15—H15C	109.5
C8—C7—H7A	109.3	H15B—C15—H15C	109.5
C6—C7—H7B	109.3	O5—C16—C16i	113.8 (3)
C8—C7—H7B	109.3	O5—C16—H16A	108.8
H7A—C7—H7B	108.0	C16i—C16—H16A	108.8
C9—C8—C7	114.6 (3)	O5—C16—H16B	108.8
C9—C8—C12	110.8 (3)	C16i—C16—H16B	108.8
C7—C8—C12	111.3 (3)	H16A—C16—H16B	107.7
C9—C8—H8	106.5
C1—O1—O2—C12	−44.0 (3)	C8—C9—C10—O4	−51.6 (4)
O2—O1—C1—O3	72.2 (3)	C15—C9—C10—O4	177.6 (3)
O2—O1—C1—C13	−174.5 (3)	C8—C9—C10—O5	73.6 (3)
O2—O1—C1—C2	−48.8 (3)	C15—C9—C10—O5	−57.2 (4)
C11—O3—C1—O1	−31.6 (4)	C1—O3—C11—O4	92.6 (3)
C11—O3—C1—C13	−143.8 (3)	C1—O3—C11—C12	−31.0 (4)
C11—O3—C1—C2	91.6 (3)	C10—O4—C11—O3	−180.0 (3)
O1—C1—C2—C3	94.4 (4)	C10—O4—C11—C12	−56.3 (3)
O3—C1—C2—C3	−25.9 (4)	O1—O2—C12—C11	−17.4 (3)
C13—C1—C2—C3	−145.5 (4)	O1—O2—C12—C8	−135.4 (2)
C1—C2—C3—C4	−56.7 (5)	O1—O2—C12—C4	105.6 (3)
C2—C3—C4—C5	168.8 (3)	O3—C11—C12—O2	57.2 (3)
C2—C3—C4—C12	38.4 (4)	O4—C11—C12—O2	−62.2 (3)
C3—C4—C5—C6	−179.1 (3)	O3—C11—C12—C8	171.6 (3)
C12—C4—C5—C6	−49.4 (4)	O4—C11—C12—C8	52.2 (3)
C3—C4—C5—C14	57.7 (4)	O3—C11—C12—C4	−61.0 (3)
C12—C4—C5—C14	−172.7 (3)	O4—C11—C12—C4	179.6 (2)
C14—C5—C6—C7	179.8 (3)	C9—C8—C12—O2	68.0 (3)
C4—C5—C6—C7	56.0 (4)	C7—C8—C12—O2	−163.2 (3)
C5—C6—C7—C8	−60.4 (4)	C9—C8—C12—C11	−49.4 (3)
C6—C7—C8—C9	−177.2 (3)	C7—C8—C12—C11	79.4 (3)
C6—C7—C8—C12	56.1 (4)	C9—C8—C12—C4	−177.4 (3)
C7—C8—C9—C10	−77.1 (3)	C7—C8—C12—C4	−48.6 (4)
C12—C8—C9—C10	49.9 (4)	C3—C4—C12—O2	−71.1 (3)
C7—C8—C9—C15	52.1 (4)	C5—C4—C12—O2	160.1 (3)
C12—C8—C9—C15	179.1 (3)	C3—C4—C12—C11	49.1 (4)
C11—O4—C10—O5	−69.3 (4)	C5—C4—C12—C11	−79.8 (3)
C11—O4—C10—C9	54.9 (4)	C3—C4—C12—C8	175.2 (3)
C16—O5—C10—O4	−69.2 (4)	C5—C4—C12—C8	46.4 (4)
C16—O5—C10—C9	165.7 (3)	C10—O5—C16—C16i	92.8 (4)