Absolute configuration of isoeichlerialactone

The title seco-dammarane triterpenoid, C27H42O4 (systematic name: 3-{(3S,3aR,5aR,6S,7S,9aR,9bR)-6,9a,9b-trimethyl-3-[(R)-2-methyl-5-oxotetrahydrofuran-2-yl]-7-(prop-1-en-2-yl)dodecahydro-1H-cyclopenta[a]naphthalen-6-yl}propanoic acid), has been isolated for the first time from the seeds of Aglaia forbesii. The molecule has three fused rings and all rings are in trans-fused. The two cyclohexane rings are in standard chair conformations and the cyclopentane ring adopts an envelope conformation. Its absolute configuration was determined by the refinement of the Flack parameter to 0.26 (17). In the crystal, molecules are linked into chains along [010] by O—H⋯O hydrogen bonds.


Comment
The genus Aglaia is a rich source of a number of interesting constituents, such as flavaglines, bisamides, triterpenoids, and limonoids which have insecticidal, antifungal, anti-inflammatory and cytotoxic activities (Engelmeier et al., 2000;Greger et al., 2001;Kim et al., 2006;Proksch et al., 2005). Aglaia forbesii is a large tree mainly distributed in southern Thailand.
Previous phytochemical studies on the leaves of Aglaia forbesii showed that some of the isolated compounds from this plant showed antituberculosis and antiviral activities (Joycharat et al., 2008). The title seco-dammarane triterpenoid was isolated for the first time from the seeds of Aglaia forbessi which was collected from Nakhon Si Thammarat province in the southern part of Thailand. Its absolute configuration was determined by making use of the anomalous scattering of Cu Kα X-radiation with the the Flack parameter refined to 0.26 (17). We report herein the crystal structure of the title compound. In the crystal packing ( Fig. 2), the molecules are arranged into one dimensional chains along the b axis by intermolecular O-H···O hydrogen bonds involving O atoms of propanoic acid groups (Table 1).

Experimental
The seeds of Aglaia forbesii (48 g) were air-dried and ground, and exhaustively extracted with EtOH (3 × 500 mL) at room temperature. The combined extracts were concentrated under reduced pressure to afford a brown extract (5.7 g) which was resuspended in a mixture of MeOH and water and then extracted with n-hexane, CH 2 Cl 2 , and BuOH, successively. The CH 2 Cl 2 fraction (1.87 g) was applied to column chromatography over silica gel (Merck, 0.063-0.200 mm) using gradient elution from 2% to 100% acetone in CH 2 Cl 2 , and finally washed down with MeOH. The fraction eluted with 12% acetone in CH 2 Cl 2 was further purified on columns of silica gel (CH 2 Cl 2 -acetone, 92:8 v/v) and Sephadex LH20 (CH 2 Cl 2 -MeOH, 1:1 supplementary materials sup-2 v/v) to yield the title compound (10.7 mg). Colourless needle-shaped single crystals of the title compound suitable for X-ray structure determination were recrystallized from EtOH after several days. 1 H NMR and 13 C NMR spectral data (Joycharat et al., 2010) were consistent with the X-ray structure.

Refinement
After confirming their positions from the difference map, all H atoms were placed in calculated positions with d(O-H) = 0.82 Å and d(C-H) = 0.93 Å for aromatic, 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 hydroxy and 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 0.67 Å from H26B and the deepest hole is located at 1.15 Å from C12. 1258 Friedel pairs were used to determine the absolute configuration.

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 > 2sigma(F 2 ) is used only for calculating R-factors(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.