Ergotaminine

The title compound {systematic name: (6aR,9S)-N-[(2R,5S,10aS,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-8H-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl]-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide}, C33H35N5O5, was formed by an epimerization reaction of ergotamine. The non-aromatic ring (ring C of the ergoline skeleton) directly fused to the aromatic rings is nearly planar [maximum deviation = 0.317 (4) Å] and shows an envelope conformation, whereas ring D, involved in an intramolecular N—H⋯N hydrogen bond exhibits a slightly distorted chair conformation. The structure displays chains running approximately parallel to the diagonal of bc plane that are formed through N—H⋯O hydrogen bonds.

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. It was however established based on liquid chromatography data that confirmed the epimeric purity of the obtained ergotaminine crystals. Besides the intramolecular hydrogen bonds between N2-H2 and N3 (see Table 1; not shown in Fig. 2), each molecule is connected to two adjacent molecules via intermolecular hydrogen bonds (see Table 1; see dashed green bonds in Fig. 2). As a result adjacent chains run along the [011] and [011] direction in an oppositely slanted fashion and with an inlined angle of 69.4°.

Experimental
Ergotamine tartrate was obtained from Sigma-Aldrich (Taufkirchen, Germany). The stereoselective conversion of ergotamine to ergotaminine was carried out as follows: 12.4 mg ergotamine tartrate were dissolved in a solution of 5 ml methanol and 0.5 ml water. For epimerization reaction the resulting mixture was stored in a sealed vial in darkness at ambient temperature for two weeks. As a result of the slow crystallization colorless crystals of the title compound were formed, because of a substantial solubility difference between ergotamine and ergotaminine (as reported by Stoll (1945)).

Refinement
In the absence of significant anomalous dispersion effects, Friedel pairs were merged.
The N-H and O-H H atoms were located in difference maps and fixed in their found positions (AFIX 3) with U iso (H) = 1.2 of the parent atom U eq or 1.5 U eq (C methyl , O).

a]pyrrolo[2,1-c]pyrazin-2-yl]-7-methyl-
Absolute structure: syn Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. 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.