Eplerenone ethanol solvate

Qian Yang; Wei-Dong Ye; Jian-Yong Yuan; Jing-Jing Nie; Duan-Jun Xu

doi:10.1107/S1600536808009240

. 2008 Apr 10;64(Pt 5):o829. doi: 10.1107/S1600536808009240

Eplerenone ethanol solvate

Qian Yang ^a, Wei-Dong Ye ^b, Jian-Yong Yuan ^b, Jing-Jing Nie ^a, Duan-Jun Xu ^a,^*

PMCID: PMC2961083 PMID: 21202318

Abstract

Eplerenone [systematic name: 7α-(methoxycarbonyl)-3-oxo-9α,11-epoxy-17α-pregn-4-ene-21,17-carbolactone], an aldosterone receptor antagonist, crystallizes from ethanol as a monosolvate, C₂₄H₃₀O₆·C₂H₆O. The eplerenone molecule has two five-membered rings, three six-membered rings and one three-membered ring. Both five-membered rings display envelope conformations, while the three six-membered rings assume envelope (cyclohexene), half-chair (cyclohexane sharing one edge with epoxy) and chair (other cyclohexane) conformations. The solvent molecule is disordered equally over two sites. It is linked to the eplerenone molecule by hydrogen bonds.

Related literature

For background literature, see: Grob et al. (1985 ▶). For related structures, see: Grob et al. (1997 ▶); Yang et al. (2007 ▶); Xu et al. (2007 ▶). For ring analysis, see: Spek (2003 ▶).

Experimental

Crystal data

C₂₄H₃₀O₆·C₂H₆O
M _r = 460.55
Orthorhombic,
a = 8.3236 (5) Å
b = 12.8306 (9) Å
c = 23.3173 (13) Å
V = 2490.2 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 295 (2) K
0.20 × 0.16 × 0.14 mm

Data collection

Rigaku R-AXIS RAPID IP diffractometer
Absorption correction: none
19548 measured reflections
2559 independent reflections
1955 reflections with I > 2σ(I)
R _int = 0.053

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.151
S = 1.05
2559 reflections
293 parameters
6 restraints
H-atom parameters constrained
Δρ_max = 0.30 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: PROCESS-AUTO (Rigaku, 1998 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002 ▶); program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808009240/ng2439sup1.cif

e-64-0o829-sup1.cif^{(27.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808009240/ng2439Isup2.hkl

e-64-0o829-Isup2.hkl^{(123.1KB, hkl)}

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
O8—H8A⋯O1ⁱ	0.96	2.19	3.15 (4)	178
O9—H9A⋯O1ⁱ	0.98	2.34	3.32 (4)	177

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Symmetry code: (i) Inline graphic .

Acknowledgments

The work was supported by the ZIJIN project of Zhejiang University, China.

supplementary crystallographic information

Comment

The eplerenone is known as an aldosterone receptor antagonist and can be administered in a therapeutically effective amount where use of an aldosterone receptor antagonist (Grob et al., 1985). The crystal structure of the eplerenone ethanol solvate is reported here.

The crystal of the title compound consists of eplerenone molecules and lattice ethanol molecules (Fig. 1). The molecule of eplerenone contains three six-membered rings, two five-membered rings and one three-membered ring. A ring analysis (Spek, 2003) indicates that three six-membered rings assume different conformations: chair, half-chair and envelope; both five-membered rings display the similar envelope configuration. This agrees with those found in the structure of eplerenone THF solvate (Yang et al. 2007) and in the structure of eplerenone dioxane solvate (Xu et al., 2007). The C2—C3 bond distance of 1.343 (6) Å indicates the typical C?C double bond. The C23-ester group forms an intra-molecular C—H···O hydrogen bond with the adjacent C14-methine group (Table 1). This structural feature is also found in the crystal structure of eplerenone dichloromethane solvate (Grob et al., 1997).

In the crystal structure, lattice solvent molecules are disorderly located in the cavities formed by eplerenone molecules and link with eplerenone molecules via O—H···O and C—H···O hydrogen bonding (Table 1).

Experimental

A microcrystalline powder sample of eplerenone was prepared in the manner reported by Grob et al. (1997). Single crystals of the title compound were obtained from an ethanol solution of eplerenone.