Koetjapic acid chloroform hemisolvate

The asymmetric unit of the title compound, C30H46O4·0.5CHCl3, consists of one koetjapic acid [systematic name: (3R,4aR,4bS,7S,8S,10bS,12aS)-7-(2-carboxyethyl)-3,4b,7,10b,12a-pentamethyl-8-(prop-1-en-2-yl)-1,2,3,4,4a,4b,5,6,7,8,9,10,10b,11,12,12a-hexadecahydrochrysene-3-carboxylic acid] molecule and one half-molecule of chloroform solvent, which is disordered about a twofold rotation axis. The symmetry-independent component is further disordered over two sites, with occupancies of 0.30 and 0.20. The koetjapic acid contains a fused four-ring system, A/B/C/D. The A/B, B/C and C/D junctions adopt E/trans/cis configurations, respectively. The conformation of ring A is intermediate between envelope and half-chair and ring B adopts an envelope conformation whereas rings C and D adopt chair conformations. A weak intramolecular C—H⋯O hydrogen bond is observed. The koetjapic acid molecules are linked into dimers by two pairs of intermolecular O—H⋯O hydrogen bonds. The dimers are stacked along the c axis.

The asymmetric unit of the title compound, C 30 H 46 O 4 Á-0.5CHCl 3 , consists of one koetjapic acid [systematic name: (3R,4aR,4bS,7S,8S,10bS,12aS)-7-(2-carboxyethyl)-3,4b,7,10b,-12a-pentamethyl-8-(prop-1-en-2-yl)-1,2, 3,4,4a,4b,5,6,7,8,9,10,-10b,11,12,12a-hexadecahydrochrysene-3-carboxylic acid] molecule and one half-molecule of chloroform solvent, which is disordered about a twofold rotation axis. The symmetryindependent component is further disordered over two sites, with occupancies of 0.30 and 0.20. The koetjapic acid contains a fused four-ring system, A/B/C/D. The A/B, B/C and C/D junctions adopt E/trans/cis configurations, respectively. The conformation of ring A is intermediate between envelope and half-chair and ring B adopts an envelope conformation whereas rings C and D adopt chair conformations. A weak intramolecular C-HÁ Á ÁO hydrogen bond is observed. The koetjapic acid molecules are linked into dimers by two pairs of intermolecular O-HÁ Á ÁO hydrogen bonds. The dimers are stacked along the c axis.  (1975). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 Comment n-Hexane extract of Sandoricum koetjape was reported previously to have cytotoxic and apoptotic properties on HCT-116 colon cancer cell line (Aisha et al., 2009). The koetjapic acid can be isolated from the stem bark of S. koetjape using column chromatography and was studied for cytotoxic activity (Kaneda et al., 1992). This compound was found to possess DNA polymerase β inhibition (Sun et al., 1999), ichthyotoxic (Ismail et al., 2003, and anti-inflammatory properties (Rasadah et al., 2004). The structure of koetjapic acid was established previously by several research groups from spectral evidence (Kaneda et al., 1992;Rasadah et al., 2004;Sun et al., 1999). Herein we describe a new simple method to purify koetjapic acid from Sandoricum koetjape. This method utilizes two steps of crystallization process but without the use of column chromatography.

Related literature
The asymmetric unit of title compound, consists of one koetjapic acid molecule and half a molecule of disordered chloroform solvent (Fig. 1). The koetjapic acid contains fused four-ring system, A/B/C/D (Scheme 1). The A/B, B/C and C/D junctions adopt E/trans/cis configuration, respectively. The conformation of the ring A is intermediate between envelope The koetjapic acid molecules are linked into dimers by two pairs of intermolecular O1-H1···O4 and O3-H3···O2 hydrogen bonds (Table 1). The dimers are stacked along the c axis (Fig. 2).
The chloroform molecule is disordered over four sites in a void with twofold symmetry. In one set of symmetry-related sites, atom Cl2 lies on the twofold rotation axis and the three Cl sites [Cl1, Cl2, Cl1A; occupancy 0.60] are shared by two disorder components. In the other set of symmetry-related site, atoms Cl3 and Cl3A [occupancy 0.40] are shared by two disorder components with atoms Cl4 or Cl4A [occupancy 0.20] in each component. The chloroform solvent molecule lies in the cavity produced by the dimer.

Experimental
The title compound was isolated from the stem bark of Sandoricum koetjape, which was collected from the main campus of Universiti Sains Malaysia on middle of October 2009. 200 g of the dried powder was extracted with 1000 ml of n-hexane at 313 K for 24 hours with intermittent shaking. The extract was filtered and concentrated to dryness under reduced pressure at 313 K to give 10 g of solid material. 10 g of the extract was dissolved in 50 ml, 1:1, methanol-acetone and was kept at 253 K. After 24 hours, a white precipitate was formed. The solid was filtered and washed thrice with ice-chilled chloroform.
The compound was crystallized from chloroform to give colourless prism-shaped crystals (400 mg). Single crystals suitable for X-ray analysis were obtained by slow evaporation of a chloroform solution at room temperature.

Special details
Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ.