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

Volume 65
Part 2
Pages o358-o359
February 2009

Received 15 December 2008
Accepted 15 January 2009
Online 23 January 2009

Key indicators
Single-crystal X-ray study
T = 100 K
Mean (C-C) = 0.002 Å
R = 0.026
wR = 0.069
Data-to-parameter ratio = 13.6
Details

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

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-HO 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
= 113.14 (1)°
V = 1006.29 (9) Å³
Z = 2
Cu K radiation
= 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 > 2(I)
R_int = 0.019

Refinement

R[F² > 2(F²)] = 0.026
wR(F²) = 0.069
S = 1.08
3623 reflections
267 parameters
1 restraint
H-atom parameters constrained
_max = 0.25 e Å^-3
_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-HA	D-H	HA	DA	D-HA
O6-H6O7ⁱ	0.82	1.99	2.7279 (14)	150
O7-H7O2ⁱⁱ	0.82	2.18	2.8409 (13)	138
O7-H7O4ⁱⁱ	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).

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BI2336 ).

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.
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.
Bruker (2005). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.
Flack, H. D. (1983). Acta Cryst. A39, 876-881.
Lisgarten, J. N., Potter, B. S., Bantuzeko, C. & Palmer, R. A. (1998). J. Chem. Crystallogr. 28, 539-543.
Pu, Y. M., Torok, D. S., Ziffer, H., Pan, X.-Q. & Meshnick, S. R. (1995). J. Med. Chem. 38, 4120-4124.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.
Zheng, G. Q. (1994). Planta Med. 60, 54-58.

organic compounds