1-Bromo-2-(10β-dihydroartemisinoxy)ethane

The title compound, C17H27BrO5, DEB, is a derivative of artemisinin which is used in malara therapy. The OR-group at C12 is cis to the CH3-group at C11 and axially oriented on ring D which has a chair conformation. The crystal packing is stabilized by several weak intermolecular C—H⋯O interactions, which combine to form a C—H—O bonded network parallel to (001).

The title compound, C 17 H 27 BrO 5 , DEB, is a derivative of artemisinin which is used in malara therapy. The OR-group at C12 is cis to the CH 3 -group at C11 and axially oriented on ring D which has a chair conformation. The crystal packing is stabilized by several weak intermolecular C-HÁ Á ÁO interactions, which combine to form a C-H-O bonded network parallel to (001).
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: ORTEP-3 for Windows (Farrugia, 1997) and SCHAKAL99 (Keller, 1999); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2009  Malaria is one of the top three priority diseases of the WHO and is becoming a worldwide threat because of its wide spread resistance to current anti-malaria drugs (World Health Organization, 2008). Artemisinin and its derivatives currently represent the most effective group of compounds against multidrug-resistant malaria with a rapid onset of action and a short half life. However, when artemisinin analogs are used as monotherapy it results in significant recrudescence (Ploypradith, 2004). Therefore it is recommended by the WHO that all uncomplicated P. falciparum infections should be treated with an artemisinin-based combination therapy (ACT).
When DHA is prepared from artemisinin by reduction, it exists as a mixture of α-and β-isomers. Luo and co-workers (Luo et al. 1984) determined that these isomers can exist in two conformations of ring D, a half-chair form and a half-boat form. DEB was tested in vitro against Plasmodium falciparum sensitive (D10) and resistant (Dd2) strains, but did not show any improved activity with respect to the reference drug: dihydroartemisinin (DHA).
DEB was synthesized from the reaction of DHA with bromoethanol. DHA was supplied as a mixture of anomers. With the formation of DEB the OR-group at C12 is positioned cis to the CH 3 -group at C11 and axially oriented on ring D. Therefore, DEB can be assigned to the β-chair series. The rings in the title compound have also been previously labeled as rings A, B, C and D (scheme). Ring A has a twist boat conformation with puckering parameters (Cremer & Pople, 1975) Q, θ and φ of 0.739 (2), 94.21 (15)° and 274.46 (16)°, respectively ( Fig. 1). Ring B has a distorted boat conformation and ring C is in a slightly distorted chair conformation with puckering parameters Q, θ and φ of 0.539 (3), 8.6 (3)° and 195.6 (18)°. Ring D is in a chair conformation with puckering parameters Q, θ and φ of 0.532 (2), 178.2 (3)° and 73 (11)°. Crystal packing in DEB is stabilized by a several C-H···O weak intermolecular interactions (Table 1)  These combine to form a C-H-O bonded network parallel to (001).

Experimental
The title compound was prepared as described by Li and co-workers (Li et al., 2000). The product was recrystallized from methanol using a slow evaporation technique at room temperature with a 71% yield of white needle-like crystals. IC 50 (ng/ml) of the title compound (DEB): D10 = 41.39, Dd2 = 129.47 IC 50 (ng/ml) of Dihydroartemisinin: D10 = 1.45, Dd2 = 0.59.

Refinement
All H atoms were positioned geometrically, and allowed to ride on their parent atoms, with Atom-H bond lengths of 1.00 Å (CH), 0.99 Å (CH 2 ), or 0.98 Å (CH 3 ). Isotropic displacement parameters for these atoms were set to 1.2 times (CH and CH 2 ) or 1.5 times (CH 3 ) U eq of the parent atom.    Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.