(3S)-14,16-Dihydroxy-3-methyl-3,4,5,6,9,10,11,12-octahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione (zearalanone) monohydrate

The absolute configuration of the title compound, C18H24O5·H2O, was not been determined by anomalous-dispersion effects, but has been assigned by reference to an unchanging chiral centre in the synthetic procedure. Intramolecular O—H⋯O hydrogen bonds stabilize the molecular conformation. In the crystal, O—H⋯O hydrogen bonds link the main molecules and the water molecules, forming an infinite three-dimensional network.

The absolute configuration of the title compound, C 18 H 24 O 5 ÁH 2 O, was not been determined by anomalousdispersion effects, but has been assigned by reference to an unchanging chiral centre in the synthetic procedure. Intramolecular O-HÁ Á ÁO hydrogen bonds stabilize the molecular conformation. In the crystal, O-HÁ Á ÁO hydrogen bonds link the main molecules and the water molecules, forming an infinite three-dimensional network.

Related literature
For the preparation of zearalanone from natural zearalenone, see: Urry et al. (1966). For the crystal structures of zearalenone and its derivatives, see: Panneerselvam et al. (1996); Gelo-Pujić et al. (1994); Zhao et al. (2008). For the estrogenic and anabolic effects of zearalenone and its derivatives, see: Mirocha et al. (1968). For the exploitation of zearalanone as an internal standard, see: Berthiller et al.   Table 1 Hydrogen-bond geometry (Å , ).  ZEN is a well known crop contaminant produced by a variety of Fusarium fungi. Its crystal structure was elucidated by Panneerselvam and colleagues (1996). Since the first isolation of ZEN from Fungi, a range of structurally closely related analoga have been isolated or prepared from ZEN (Gelo-Pujić et al., 1994, Zhao et al., 2008.

Experimental
These RALs exhibit interesting estrogenic and anabolic effects due to their coupling with the estrogenic receptors alpha and beta (Mirocha et al., 1968). Hence, ZAN was patented as a growth promoter in cattle as early as 1966 (U. S. P., 3239354). Furthermore, ZAN is not occurring in food, wherefore it was exploited as an internal standard for ZEN and its metabolites (Berthiller et al., 2005, Maragou et al., 2008, Ren et al., 2007, Shin et al., 2009).
The compound crystallizes in the orthorhombic space group P2 1 2 1 2 1 . The compound has a macrocyclic structure. The molecular structure of the compound and the atom-labeling scheme are shown in Fig 1. The absolute configuration could not be defined confidently based on the single-crystal diffraction data. The isomeric purity of the title compound was confirmed by 1 H-NMR, HPLC-DAD and -MS/MS data. Besides the intramolecular hydrogen bonds between O5-H5A and O2, each molecule is connected to three adjacent water molecules via intermolecular hydrogen bonds (see dashed red bonds in Fig. 2). As a result a three dimensional network is formed.

Experimental
Zearalanone was obtained from Toronto Research Chemicals (Canada, purity 98.0%). 5 mg (15.6 µmol) were weighed in a 1.5 ml HPLC glass vial and solved in 0.5 ml DCM. Subsequently, 0.3 ml of n-Hexane were added. Colorless crystals of the title compound were formed after 7 days of slow solvent evaporation at room temperature.

Refinement
All H-atoms were positioned geometrically and refined using a riding model with d(C-H) = 0.93 Å, U iso =1.2U eq (C) for aromatic 0.98 Å, U iso = 1.2U eq (C) for CH, 0.97 Å, U iso = 1.2U eq (C) for CH 2 , 0.96 Å, U iso = 1.5U eq (C) for CH 3 atoms, and 0.82 Å, U iso = 1.5U eq (C) for hydroxyl groups. The water hydrogen atoms were treated independently. In the absence of significant anomalous dispersion effects, Friedel pairs were merged.

Figure 1
ORTEP representation of the title compound with atomic labeling shown with 30% probability displacement ellipsoids. 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.