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

Sarah Drzymala; Werner Kraus; Franziska Emmerling; Matthias Koch

doi:10.1107/S1600536812018168

. 2012 Apr 28;68(Pt 5):o1577. doi: 10.1107/S1600536812018168

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

Sarah Drzymala ^a,^*, Werner Kraus ^a, Franziska Emmerling ^a, Matthias Koch ^a

PMCID: PMC3344672 PMID: 22590434

Abstract

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.

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. (2005 ▶); Maragou et al. (2008 ▶); Ren et al. (2007 ▶); Shin et al. (2009 ▶).

Experimental

Crystal data

C₁₈H₂₄O₅·H₂O
M _r = 338.39
Orthorhombic,
a = 8.2727 (11) Å
b = 24.579 (3) Å
c = 9.3703 (14) Å
V = 1905.3 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.45 × 0.25 × 0.1 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T _min = 0.151, T _max = 0.477
20473 measured reflections
4626 independent reflections
2870 reflections with I > 2σ(I)
R _int = 0.109

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.134
S = 0.90
4626 reflections
225 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: APEX2 (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT (Bruker, 2001 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812018168/fj2544sup1.cif

e-68-o1577-sup1.cif^{(24.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812018168/fj2544Isup2.hkl

e-68-o1577-Isup2.hkl^{(226.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812018168/fj2544Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4A⋯O6	0.82	1.87	2.693 (2)	176
O5—H5A⋯O2	0.82	1.86	2.581 (2)	147
O6—H6C⋯O3ⁱ	0.96 (2)	1.85 (2)	2.810 (3)	178 (3)
O6—H6D⋯O5ⁱⁱ	0.96 (2)	1.95 (2)	2.887 (2)	164 (2)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank Dr Robert Köppen from the Federal Institute for Materials Research and Testing (BAM) for his assistance in obtaining zearalanone crystals.

supplementary crystallographic information

Comment

Zearalanone (ZAN) is a semisynthetic resorcylic acid lactone (RAL) belonging to the group of Zearalenone (ZEN) analoga. ZAN was first prepared by catalytic hydrogenation of the double bond between C11 and C12 of natural ZEN (Urry et al., 1966).

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).

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 P2₁2₁2₁. 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 ¹H-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.