Crystal and molecular structure of jatrophane diterpenoid (2R,3R,4S,5R,7S,8S,9S,13S,14S,15R)-2,3,8,9-tetraacetoxy-5,14-bis(benzoyloxy)-15-hydroxy-7-(isobutanoyloxy)jatropha-6(17),11(E)-diene

A jatrophane diterpenoid was isolated from the fructus of Euphorbia sororia and its structure and absolute configuration have been established by X-ray crystallographic analysis.


Chemical context
Macrocyclic diterpenes demonstrate a range of biological effects, including modulability of multidrug resistance, cytotoxicity, antiproliferative, anti-inflammatory, and antimicrobial activities (Hohmann et al., 2002;Shi et al., 2008;Vasas & Hohmann, 2014). Jatrophane diterpenes, which possess fused five-and twelve-membered carbon rings are usually substituted by a variety of aryl and benzyl groups. The title compound ES2, a new type of jatrophane diterpenoid ester isolated from the fruits of Euphorbia sororia is widely used as a traditional Uyghur medicine in China (Lu et al., 2014) and shows promising chemo-reversal abilities compared to verapamil . ES2 has demonstrated cytotoxicity and anti-multidrug resistance activity in multidrugresistant MCF-7/ADR breast cancer cells (Fang et al., 2018). The structure of this compound has been determined by X-ray structure analysis and reported in the present article.

Supramolecular features
In the crystal, two C-HÁ Á ÁO hydrogen bonds form between the methyl group (C37) of the 8-acetoxy group as donor and the carbonyl O atoms of the acetoxy substituents in positions 2 (O15B) and 9 (O9) as acceptors (Table 1). These interactions link molecules related by symmetry operation 2 1 and translation parallel to the a axis, respectively. Together they form extended supramolecular columns parallel to the a axis (Fig. 2). Only van der Waals interactions occur between the columns. The OH group is not involved in intermolecular hydrogen-bonding interactions, only intramolecular.

Figure 1
The molecular structure of the title compound ES2 with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Similar compounds studied are EZIHUS, EZIJAA and EZIJEE (Esposito et al., 2016), PEMQON (Kar et al., 1998), SUXHUO (Liu & Tan, 2001), and altotibetin A and altotibetin B (OKICIU and OKICOA; Li et al., 2003). In ZUKLIA and ZUKLOG (terracinolide A and terracinolide B; Marco et al., 1996) and ZELWEV01 , a lactone ring substituent is present, so the configuration at the C5-C6 ring junction is cis. The structure of EZIJAA, (2R,3R,4S,5R,7R,8R,9R,13S,-15R)-2,9-diacetoxy-3,8,15-trihydroxy-5,7-dibenzoyloxy-14oxojatropha-6(17),11(E)-diene diethyl ether solvate (Esposito et al., 2016) is the most similar to that of the title compound. Both structures have trans-conjugated five-and twelve-membered rings, but the envelope conformation of the former in EZIJAA is different. Atom C4 (not C15 as in title structure) is out of the mean plane. In both structures, the substituent at C5 is a Bz-group, but in EZIJAA the benzyl ring is less inclined to the mean plane of atoms C5/O5/C25/O4/C26 [5.67 (4) compared to 15.50 (2) in the title compound]. In both structures, a strong intramolecular hydrogen bond is observed between Bz-group at C5 and the hydroxyl group at C15. However, the presence of three hydroxyl substitutes at C3, C8 and C15 leads to the appearance of four intramolecular hydrogen bonds in the structure of EZIJAA, which is more loosely packed than that of the title compound and which contains voids.

Synthesis and crystallization
The process of extraction and isolation of ES2 is described in detail by Lu et al. (2014). Colourless prismatic single crystals were prepared by slow evaporation of the solvent from an ethanol solution at room temperature. The absolute configuration was been determined as 2R,3R,4S,5R,7S,8S,-9S,13S,14S,15R, the same as reported by Lu et al. (2014).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms were placed in idealized positions (O-H = 0.82, C-H = 0.93-0.98 Å ) and refined as riding atoms. For the hydroxyl group, possible hydrogen-bonding positions were taken into account in generating the idealized position (AFIX 83). U iso (H) values were set to a multiple of U eq (C,O) with multipliers of 1.5 for CH 3 and OH, and 1.2 for CH and CH 2 units, respectively.
A large difference peak and Hirshfeld test deviations indicated disorder of the C2-acetoxy group. The disordered atoms were modelled over two positions using the PART instruction with occupancies for the dominant and minor positions of 83% and 17%, respectively. A bond distance restraint to a target value of 1.4 (1) Å was used in the disordered acetyl group (C21B-C22B).    PRO (Agilent, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: XP (Siemens, 1994).   (11) 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. 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ.