Absolute configuration of isovouacapenol C

The title compound, C27H34O5 {systematic name: (4aR,5R,6R,6aS,7R,11aS,11bR)-4a,6-dihydroxy-4,4,7,11b-tetramethyl-1,2,3,4,4a,5,6,6a,7,11,11a,11b-dodecahydrophenanthro[3,2-b]furan-5-yl benzoate}, is a cassane furanoditerpene, which was isolated from the roots of Caesalpinia pulcherrima. The three cyclohexane rings are trans fused: two of these are in chair conformations with the third in a twisted half-chair conformation, whereas the furan ring is almost planar (r.m.s. deviation = 0.003 Å). An intramolecular C—H⋯O interaction generates an S(6) ring. The absolute configurations of the stereogenic centres at positions 4a, 5, 6, 6a, 7, 11a and 11b are R, R, R, S, R, S and R, respectively. In the crystal, molecules are linked into infinite chains along [010] by O—H⋯O hydrogen bonds. C⋯O [3.306 (2)–3.347 (2) Å] short contacts and C—H⋯π interactions also occur.


Comment
The plants in Caesalpiniaceae are rich sources of cassane furanoditerpenes. The extracts from plants in this family have been found to possess bioactivities such as antiviral (Jiang et al., 2001), antitumor (Che et al., 1986) and HIV-1 protease inhibitory (Tewtrakul et al., 2003) properties. Caesalpinia pulcherrima (L.) Swartz, locally known as "Hang Nok Yung Thai" (Smitinand & Larson, 2001) is a large perennial shrub or small tree that is widely distributed in tropical areas. The plant has been used for ornamental (Smitinand & Larson, 2001), abortifacient and emmenagogue purposes. Isolated compounds from C. pulcherrima exhibits potential fertility regulating, antitumor (Che et al., 1986), antibacterial, antifungal (Ragasa et al., 2002) and anti-tubercular activities (Promsawan et al., 2003). These compounds are also active against DNA repair-deficient yeast mutant (Patil et al., 1997). In the course of our research of chemical constituents and bioactive compounds from the roots of C. pulcherrima which were collected from Songkhla province in the southern part of Thailand, the title cassane furanoditerpene (I), also known as isovouacapenol C (Ragasa et al., 2002) or 6β-cinnamoyl-7β-hydroxyvouacapen-5α-ol (Promsawan et al., 2003), was isolated. The previous reports showed that (I) exhibits moderate antimicrobial (Ragasa et al., 2002) and cytotoxic activities (Promsawan et al., 2003). 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 0.07 (17). We report herein the crystal structure of (I). Fig. 1 shows that the molecule of (I) is constructed from the fusion of three cyclohexane rings and a furan ring. The three cyclohexane rings are trans-fused. Two cyclohexane rings A and B are in standard chair conformations whereas ring C adopts twisted half-chair conformation with the puckered C8 and C9 atoms having the maximum deviation of -0.306 (1) and 0.280 (2) Å, respectively from the best plane of the remaining four atoms (C11-C14) and with the puckering parameters Q = 0.4532 (17) Å and θ = 47.1 (2)° and φ = 23.0 (3)° (Cremer & Pople, 1975). The furan ring (C12/C13/C15/C16/O1) is planar (rms 0.001 (2) Å). Atoms of the benzoate moiety (C21-C27/O3/O4) lie on the same plane with the rms 0.009 (2) Å. The orientation of the benzoate group is described by the torsion angles C21-O3-C6-C5 = 136.98 (16)° and C21-O3-C6-C7 = -99.22 (17)°. The bond angles around C12 and C13 atoms are indicative of sp 2 hybridization for these atoms and the bond length of 1.344 (3) Å confirmed the C12 ═C13 bond. The bond distances in (I) are within normal ranges (Allen et al., 1987) and comparable with the related structures which are caesalmin C, D, E, F and G (Jiang et al., 2001). The absolute configuration at positions 4a, 5, 6, 6a, 7, 11a and 11b of the isovouacapenol C or atoms C5, C6, C7, C8, C14, C9 and C10 were R,R,R,S,R,S,R configurations.
The combined extracts were concentrated under reduced pressure to afford a dark brownish extract (75.3 g) which was further purified by quick column chromatography (QCC) over silica gel using hexane as eluent and increasing polarity with EtOAc and MeOH to afford 16 fractions (F1-F16). Fraction F4 was then concentrated under reduced pressure to yield the title compound as white solid (10.0 g). Colorless block-shaped single crystals of the compound (I) were recrystallized from CH 2 Cl 2 by the slow evaporation of the solvent at room temperature after several days, Mp. 389-391 K.

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 calculat-

sup-4
ing 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.