Crystal structure of ochraceolide A isolated from Elaeodendron trichotomum (Turcz.) Lundell

The crystal structure of the triterpene lactone ochraceolide A (3-oxolup-20 (29)-en-30,21α-olide) isolated from Elaeodendron trichotomum (Turcz.) Lundell is reported.


Chemical context
Ochraceolides A-E are a group of cytotoxic lupane -lactones isolated from the Celastraceae family. Ochraceolide A was firstly isolated from Kokoona ochracea (Elm.) Merril stem bark (Ngassapa et al., 1991) and afterwards from Lophopetalum wallichii (Sturm et al., 1996) and Cassine xylocarpa (Callies et al., 2015). The title compound has shown significant cytotoxic activity against murine lymphocytic leukemia cells (P-388) with an ED 50 of 0.6 mM; human oral epidermoid carcinoma (KB-3) with an ED 50 of 6.0 mM; and hormonedependent breast cancer with an ED 50 of 9.9 mM (Ngassapa et al., 1991;Sturm et al., 1996). In the same way, this compound has exhibited significant inhibitory activity in the FPTase assay with an IC 50 of 2.2 mM (Sturm et al., 1996) and inhibitory effects of human immunodeficiency virus type 1 replication with an IC 50 of 39.0 mM (Callies et al., 2015). Ochraceolide A is part of the structure of the Diels-Alder adduct (i.e. celastroidine A or volubilide) isolated from Hippocratea celastroides K. (Jimé nez-Estrada et al., 2000) and Hyppocratea volubilis L. (Alvarenga et al., 2000). In these publications, the crystal structure of the adduct was reported as a solvate of dichloromethane and toluene, respectively. The X-ray analysis showed that the Diels-Alder adduct was integrated by the triterpene ochraceolide A and a theoretical diterpene, in which the former seems to have acted as dienophile and the latter as diene in the biosynthesis. Herein the first isolation of ochraceolide A from Elaeodendron trichotomum (Turcz.) Lundell stem bark is reported and the crystal structure described.

Supramolecular features
In the crystal, molecules are linked by weak C-HÁ Á ÁO hydrogen bonds (Table 1, Fig. 2). The lactone and A rings of adjacent molecules interact through two hydrogen bonds (C2-H2AÁ Á ÁO2 and C24-H24AÁ Á ÁO3) in a head-to-tail arrangement, forming chains along [001]. These chains are further connected through a weak hydrogen bond between the oxygen of the ketone group (O1) and a methylene group on the C ring (C12), forming an overall three-dimensional network.

Isolation and crystallization
Elaeodendron trichotomum (Turcz.) Lundell was collected from Chunchucmil, Yucatá n, Mé xico (20 o 51.032 0 N, 90 o 11.488 0 W). A voucher specimen (JTun2328) was deposited at the Herbarium Alfredo Barrera Marín, Universidad Autó noma de Yucatá n, Mé xico. Dried and milled stem bark (2100 g) was exhaustively extracted by dichloromethane using a Soxhlet extraction apparatus to yield 184.2 g of crude extract. A portion of the extract (100 g) was chromatographed on silica gel (40-60 mm) using a gradient elution with nhexane-ethyl acetate (10-100% ethyl acetate), to obtain 44 fractions. Single crystals suitable for X-ray structure analysis were obtained by slow evaporation of the mixture of solvents present in fractions 7-10 at room temperature.

Figure 1
The molecular structure of the title compound with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radius.

Special details
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.