17βH-Periplogenin, a cardiac aglycone from the root bark of Periploca sepium Bunge

The title compound {systematic name: 4-[(3S,5S,8R,9S,10R,13R,14S,17S)-3,5,14-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]furan-2(5H)-one}, C23H34O5, was isolated from the roots of Periploca sepium Bunge, a famous Chinese traditional herbal medicine. The three six-membered rings adopt chair conformations, the cyclopentane ring displays an approximate envelope conformation (with the C atom bearing the methyl substituent at the flap) and the five-membered lactone ring adopts an essentially planar [maximum deviation of 0.004 (8) Å] conformation. In the crystal, molecules are linked into helical chains along [010] by O—H⋯O hydrogen bonds and weak C—H⋯O interactions. Two intramolecular O—H⋯O hydrogen bonds are also present.


Related literature
For the botanical and medicinal background to Periploca sepium Bunge, see: Li & Liu (2004); Yang et al. (2006). For the previous preparation and chemical structure determination of the title compound, see: Furuya et al. (1988); Kawaguchi et al. (1998) Table 1 Hydrogen-bond geometry (Å , ).  Liu, 2004;Yang et al., 2006). Its root bark, which is officially listed in the Chinese Pharmacopoeia under the name Cortex Periploca (Xiangjiapi in Chinese), has been frequently used to treat rheumatism and strengthen tendons and bones.
The title compound, 17βH-periplogenin, which has been previously obtained as a biotransformation product of digitoxigenin (Furuya et al., 1988;Kawaguchi et al., 1998), was isolated from the root bark of Periploca sepium Bunge in our recent investigation. To the best of our knowledge, this is its first isolation from plant material. The isolated compound was identified by NMR spectra, which were compared with the previous report (Furuya et al., 1988).
The crystal structure of 17βH-periplogenin has not yet been reported. In view of this, the crystal structure determination of the title compound was carried out and the results are presented here.
As shown in Fig. 1, the molecule consists of three six-membered rings (A, B and C), one cyclopentane ring (D) and one five-membered lactone ring. Rings A:B, B:C and C:D are cis-, trans-and cis-fused, respectively. The three sixmembered rings adopt chair conformations, the cyclopentane ring displays an approximate envelope conformation with C13 as the flap atom, and the five-membered lactone ring adopts a planar conformation.

Experimental
The air-dried and powdered roots of Periploca sepium Bunge (2.0 kg) were extracted with 70% EtOH (3×10 l, 3×2.0 h, 85 °C) under reflux conditions to give a crude extract, which was suspended in H 2 O and successively partitioned with LH-20 (CHCl 3 /MeOH, 1:1) to give 6 subfractions: SFr. 1-6. SFr. 4 (0.9 g) was then subjected to reverse phase preparative HPLC [Waters preparative HPLC system; XTERRA PREP MS C18 column, 5 µm, 19 mm × 150 mm; sample loading 30 -60 mg/injection; the column was eluted with CH 3 OH/H 2 O system (52:48) at a flow rate of 16 ml/min] to provide the title compound (t R = 4.81 min, 26 mg). 1 H and 13 C NMR spectroscopic data of this compound were recorded on a Bruker-AV-400 spectrometer, using CD 3 OD as solvent and Me 4 Si as internal standard. The stereochemistry was established by the X-ray diffraction experiment.

Refinement
In the absence of significant anomalous scattering effects, Friedel pairs were merged. Initially all H-atoms were located in a difference Fourier map and at the last stage these H-atoms were geometrically treated.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 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.