(3β,18β,20β)-N-Ethoxycarbonylmethyl-3-nitrato-11-oxoolean-12-ene-29-carboxamide methanol monosolvate

The title compound, C34H52N2O7·CH4O, is the methanol solvate of a difunctionalized derivative of the therapeutic agent 18β-glycyrrhetinic acid, a pentacyclic triterpene. The five six-membered rings of the glycyrrhetinic acid moiety show normal geometries, with four rings in chair conformations and the unsaturated ring in a half-chair conformation. This moiety is substituted by a nitrate ester group and an O-ethylglycine group. In the crystal, the nonsolvent molecules are packed parallel to (010) in a herringbone fashion with the nitrato, ethylglycine and methanol-O atom being proximate. The methanol solvent molecule is anchored via a donated O—H⋯Oacyl and an accepted N—H⋯O hydrogen bond, giving rise to infinite zigzag chains of hydrogen bonds parallel to [100]. Two weak intermolecular C—H⋯O interactions to the methanol and to an acyl oxygen establish links along [100] and [010], respectively.

The title compound, C 34 H 52 N 2 O 7 ÁCH 4 O, is the methanol solvate of a difunctionalized derivative of the therapeutic agent 18-glycyrrhetinic acid, a pentacyclic triterpene. The five six-membered rings of the glycyrrhetinic acid moiety show normal geometries, with four rings in chair conformations and the unsaturated ring in a half-chair conformation. This moiety is substituted by a nitrate ester group and an O-ethylglycine group. In the crystal, the nonsolvent molecules are packed parallel to (010) in a herringbone fashion with the nitrato, ethylglycine and methanol-O atom being proximate. The methanol solvent molecule is anchored via a donated O-HÁ Á ÁO acyl and an accepted N-HÁ Á ÁO hydrogen bond, giving rise to infinite zigzag chains of hydrogen bonds parallel to [100]. Two weak intermolecular C-HÁ Á ÁO interactions to the methanol and to an acyl oxygen establish links along [100] and [010], respectively.

Related literature
For overviews on the therapeutic aspects of glycyrrhetinic acid, see: Baran et al. (1974); Asl & Hosseinzadeh (2008).   Table 1 Hydrogen-bond geometry (Å , ).  al., 2010;Czollner et al., 2011). In the title compound these modifications comprised the introduction of an O-ethylglycine group N-bonded to the COOH group of GA, and, as an uncommon feature, a nitrate ester group replacing the 3hydroxy group of GA. The compound was then crystallized from methanol to give the stoichiometric crystalline methanol solvate (I). A view of the asymmetric unit is shown in Fig. 1. The GA fragment (C1 through C30, O1, O4, O5) features usual bond lengths, bond angles, and conformation (Campsteyn et al., 1977;Alvarez-Larena et al., 2007;Beseda et al., 2010;Czollner et al., 2011). There are four six-membered saturated carbocycles (A, B, D, and E) in chair and the unsaturated ring C in half-chair conformation (Fig. 2). The carboxamide group O5═C29-N2 is endo-oriented with respect to the amide nitrogen N2 (C19-C20-C29-N2 = -28.1 (3)°), in contrast to a propargyl amide derivative of GA, where it is exo-oriented (Czollner et al., 2011; corresponding torsion angle 162.3°). In the crystal lattice of (I) the nonsolvent molecules are arranged in undulating layers parallel to (010) and adopt a typical herring-bone pattern within these layers (Fig. 3). These layers repeat by 2 1 axes parallel to [010]. The oxygen and nitrogen bearing ends of the GA molecules and the methanol solvent molecules are accumulated in reagions near z ≈ 0, 1/2, and 1, and are crosslinked by O-H···O, N-H···O and C-H···O interactions ( Table 1). The most prominent of them are the hydrogen bonds O8-H8···O5 and N2-H2n···O8 i , which are donated and accepted by the methanol molecule. The methanol molecule and the carboxamide moiety O5═C29-N2 thereby build up an infinite zigzag hydrogen bond chain parallel to [100], as shown in  (Table 1; cut-off values are H···O ≤ 2.60 Å, X-H···O ≥ 120°).

Experimental
To a stirred solution of acetic anhydride (5 ml) and concentrated nitric acid (2 ml) was added N-(ethoxycarbonylmethyl)-3-hydroxy-11-oxo-olean-12-ene-29-carboxamide (555 mg, 1.0 mmol; compound 26f of Beseda et al., 2010) at 273 K. After 30 min the reaction mixture was dropped to 200 ml of ice water. The solid product obtained was filtered, dried and recrystallized from 3 ml of dichloromethane and 5 ml of n-hexane to yield 400 mg (66.6%) of the desired product as colourless powder. An analytical sample of (I) was then obtained by recrystallization from methanol.

Refinement
All H atoms were placed in calculated positions and thereafter treated as riding. A torsional parameter was refined for each methyl group. U iso (H) = 1.2U eq (C non-methyl ) and U iso (H) = 1.5U eq (C methyl ) were used. Because of insignificant anomalous dispersion effects, the 4435 Friedel pairs were merged prior to the final refinement. The absolute structure of the parent compound 18β-glycyrrhetinic acid is known.

Figure 1
The asymmetric unit of (I), with displacement ellipsoids for the non-H atoms drawn at the 50% probability level. Red capitals are the ring designations.  The molecular structure of (I) in a side-view showing the conformation of the rings more clearly. H atoms have been omitted for clarity.   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.68 e Å −3 Δρ min = −0.38 e Å −3