Redetermined structure, intermolecular interactions and absolute configuration of royleanone

The structure of the title diterpenoid, C20H28O3, {systematic name: (4bS,8aS)-3-hydroxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-1,4-dione} is confirmed [Eugster et al. (1993 ▶). Private communication (refcode HACGUN). CCDC, Union Road, Cambridge] and its packing is now described. Its absolute structure was established by refinement against data collected with Cu radiation: the two stereogenic centres both have S configurations. One cyclohexane ring adopts a chair conformation whereas the other cyclohexane ring is in a half-chair conformation and the benzoquinone ring is slightly twisted. An intramolecular O—H⋯O hydrogen bond generates an S(5) ring motif. In the crystal, molecules are linked into chains along [010] by O—H⋯O hydrogen bonds and weak C—H⋯O interactions. The packing also features C⋯O [3.131 (3) Å] short contacts.


Comment
The extracts of Verbenaceae plants have been found to possess anti-HIV-1 integrase activity (Bunluepuech & Tewtrakul, 2009) and cytotoxicity (Suresh et al., 2011). During the course of our study of chemical constituents and bioactive compounds from Premna obtusifolia (Verbenaceae), the title diterpenoid (I), which is known as royleanone (Edwards et al., 1962;Tezuka et al., 1998) was isolated from the roots of this plant. Compound (I) was reported to show significant biological properties such as antioxidant (Kabouche et al., 2007) and cytotoxic activities (Slame˘nová et al., 2004). The absolute configuration of (I) was determined by making use of the anomalous scattering of Cu Kα X-radiation with the Flack parameter being refined to 0.11 (19). We herein report the crystal structure of (I).

Experimental
The air-dried roots of premna obtusifolia (4.5 kg) were extracted with hexane (2 × 20 l) at room temperature. The combined extracts were concentrated under reduced pressure to give a dark yellow extract (40.0 g) which was subjected to quick column chromatography (QCC) over silica gel using solvents of increasing polarity from n-hexane to EtOAc to afford 7 fractions (F1-F7). Fraction F2 was further purified by quick column chromatography using hexane, yielding the title compound (6.1 mg). Yellow blocks were recrystallized from CH 2 Cl 2 by the slow evaporation of the solvent at room temperature after several days, M.p 451-453 K.

Refinement
The hydroxy H atom was located from the difference map and refined isotropically. The remaining H atoms were placed in calculated positions with (C-H) = 0.98 for CH, 0.97 for CH 2 and 0.96 Å for CH 3 atoms. The U iso values were constrained to be 1.5U eq of the carrier atom for methyl H atoms and 1.2U eq for the remaining H atoms. A rotating group model was used for the methyl groups. The highest residual electron density peak is located at 0.74 Å from C10 and the deepest hole is located at 0.72 Å from C2. 699 Friedel pairs were used to determine the absolute configuration. Fig. 1. The structure of (I), showing 40% probability displacement ellipsoids. The hydrogen bond is shown as a dashed line. (4bS,8aS)-3-hydroxy-2-isopropyl-4b, 8,8-trimethyl-4b,5,6,7,8,8a,9,10-

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.