Crystal structure and Hirshfeld surface analysis of 2-oxo-13-epi-manoyl oxide isolated from Sideritis perfoliata

In the crystal of the title compound, molecules are linked by C—H⋯O hydrogen bonds, forming C(11) helical supramolecular chains along the 21 axis running parallel to [100].


Chemical context
The genus Sideritis belonging to the Lamiaceae family is represented by more than 150 species, distributed in tropical regions. Most of the species are found in the Mediterranean region. This genus is represented by 54 species in Turkey flora, 40 of which are endemic (Davis, 1982). Sideritis species have traditionally been used as herbal teas, flavouring agents and therapeutics (Danesi et al., 2013). Sideritis species include flavonoids, terpenes, iridoids, coumarins, lignanes and sterols that are responsible constituents for their pharmacological properties (Gonzá lez-Burgos et al., 2011). Sideritis species have been reported to exhibit considerable biological activities such as antioxidant (Demirtas et al., 2011), antiproliferative (Demirtas et al., 2009), and antimicrobial (Yig it Hanog lu et al., 2017) effects. The crystal structure of 2--hydroxymanoyl oxide isolated from Sideritis perfoliata has been reported on by our group (Ç elik et al., 2016). Herein, we report on the crystal structure of 2-oxo-13-epi-manoyl oxide, also isolated from S. perfoliata. ISSN 2056-9890

Supramolecular features
In the crystal, molecules pack in helical supramolecular C(11) chains along the 2 1 screw axis running parallel to the a axis, bound by C-HÁ Á ÁO hydrogen bonds ( Fig. 2 and Table 1). The chains are efficiently interlocked in the other two unit-cell directions via van der Waals interactions. Between the chains there are narrow channels which also run along the [100] direction.
In the title compound (P2 1 2 1 2 1 , Z = 4), the molecules pack in helical supramolecular chains along the 2 1 screw axis running parallel to the a axis, bound by one C-HÁ Á ÁO hydrogen bond. These chains are efficiently interlocked in the other two unit-cell directions via van der Waals interactions. In the similar compound UVEVOI (P2 1 2 1 2 1 , Z = 8), the asymmetric unit contains two independent molecules. Intermolecular O-HÁ Á ÁO hydrogen bonds connect adjacent molecules, forming C(6) helical chains located around a 2 1 screw axis running along the a-axis direction. The crystal packing of these chains is governed only by van der Waals interactions. The two asymmetric molecules lead to pseudo-4 1 symmetry in space group P2 1 2 1 2 1 . The crystal structure of the other similar compound UDATUV (P2 1 , Z = 4) is stabilized by intermolecular O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, which link the molecules into networks approximately parallel to the (110) plane. In the crystal structure of the compound RASXUE (P2 1 , Z = 4), no intermolecular hydrogen-bonding interactions were detected, but the O-HÁ Á ÁO or C-HÁ Á ÁO interactions are possible hydrogen bonds. In GAPZUT (P2 1 , Z = 6), there are three independent molecules in the asymmetric unit. In the crystal, there is no classical hydrogen bondingÁThe molecular packing is stabilized by van der Waals interactions and noor C-HÁ Á Á interactions are observed. In GAQBAC (P2 1 , Z = 2), molecules are connected by O-HÁ Á ÁO hydrogen bonds into chains propagating along the c-axis direction. Here too, noor C-HÁ Á Á interactions are observed. In LUDTOU (P2 1 , Z = 4), the structure contains a water molecule. In the crystal, molecules are A view along the a axis of the crystal packing of the title compound. H atoms not involved in these interactions have been omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of the title compound, showing the atom labelling and displacement ellipsoids drawn at the 30% probability level.
molecules, forming a three-dimensional framework. Again no or C-HÁ Á Á interactions are observed.

Hirshfeld surface analysis
A large range of properties of intermolecular close contacts of a structure can be visualized on the Hirshfeld surface with the program CrystalExplorer (Wolff et al., 2012), including d e and d i , which represent the distances from a point on the Hirshfeld surface to the nearest atoms outside (external) and inside (internal) the surface, respectively. Intermolecular distance information on the surface can be condensed into a two-dimensional histogram of d e and d i , which is a unique identifier for molecules in a crystal structure, and is known as a fingerprint plot (Rohl et al., 2008). Instead of plotting d e and d i on the Hirshfeld surface, contact distances are normalized in CrystalExplorer using the van der Waals radius of the appropriate internal (r i vdw ) and external (r e vdw ) atom of the surface: For the title compound, the three-dimensional Hirshfeld surface mapped over d norm is given in Fig. 3. Contacts with distances equal to the sum of the van der Waals radii are shown in white, and contacts with distances shorter than or longer than the related sum values are shown in red (highlighted contacts) or blue, respectively. Two-dimensional finger print plots showing the occurrence of the various intermolecular contacts are presented in Fig. 4a-d. The HÁ Á ÁH interactions appear in the middle of the scattered points in the two-dimensional fingerprint plots with an overall contribution to the Hirshfeld surface of 86.0% (Fig. 4b). The contribution from the HÁ Á ÁO/OÁ Á ÁH contacts, corresponding to C-HÁ Á ÁO interactions, is represented by a pair of sharp spikes characteristic of a strong hydrogen-bond interaction (12.6%) (Fig. 4c). The contribution of the other intermolecular contacts to the Hirshfeld surfaces is HÁ Á ÁC/CÁ Á ÁH (1.4%) (Fig. 4d)     actions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015). A view of the Hirshfeld surface of the title complex plotted over the shape-index is given in Fig. 5.

Synthesis and crystallization
The floral parts of Sideritis perfoliata (100 g) were extracted with EtOAc (3 Â 1.0 L). After removal of the solvent in vacuo, the extract (4.0 g) was subjected to Sephadex LH-20 column chromatography using methanol as the mobile phase at 0.5 ml/ min flow rate. According to TLC basis the 6-8th fractions were combined (1.2 g) and separated over silica gel column chromatography using a hexane/EtOAc (6/4) mixture. Fractions 2-4 were combined to give 2-oxo-13-epi-manoyl oxide (60 mg). After removal of the solvent, a white amorphous powder was obtained. The solid was dissolved in acetone and left to stand at room temperature for 12 h. On slow evaporation of the solvent, colourless block-like crystals were obtained.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms: C-H = 0.93-0.97 Å with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms. As the title compound is a weak anomalous scatterer, the value of the Flack parameter of À1.1 (10) is meaningless. Hirshfeld surface of the title complex plotted over the shape-index. Computer programs: APEX2 and SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012) and PLATON (Spek, 2009 Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.21 e Å −3 Δρ min = −0.25 e Å −3 Special details Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on F 2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses 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 observed criterion of F 2 > 2sigma(F 2 ) is used only for calculating -R-factor-obs 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.