Ergotaminine

Stefan Merkel; Robert Köppen; Matthias Koch; Franziska Emmerling; Irene Nehls

doi:10.1107/S1600536812003674

. 2012 Feb 4;68(Pt 3):o610–o611. doi: 10.1107/S1600536812003674

Ergotaminine

Stefan Merkel ^a, Robert Köppen ^a, Matthias Koch ^a, Franziska Emmerling ^a,^*, Irene Nehls ^a

PMCID: PMC3295412 PMID: 22412523

Abstract

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.

Related literature

Ergotaminine is an ergot alkaloid formed by, among others, the fungus Claviceps purpurea on cereal grains and grasses during the growth process; see: Crews et al. (2009 ▶); Müller et al. (2009 ▶). For investigations of the biologically inactive C8-(S)-isomer ergotaminine, see: Pierri et al. (1982 ▶); Komarova & Tolkachev (2001 ▶). For the crystal structure of ergotamine tartrate ethanol solvate, see: Pakhomova et al. (1995 ▶). For the crystal structure of ergometrinine, another C8-(S)-configured ergotalkaloid, see: Merkel et al. (2010 ▶). For the solubility of ergotaminine, see: Stoll (1945 ▶).

Experimental

Crystal data

C₃₃H₃₅N₅O₅
M _r = 581.66
Monoclinic,
a = 10.974 (3) Å
b = 9.662 (2) Å
c = 14.450 (4) Å
β = 105.059 (15)°
V = 1479.5 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.2 × 0.1 × 0.06 mm

Data collection

Bruker APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T _min = 0.879, T _max = 0.986
20196 measured reflections
2781 independent reflections
2240 reflections with I > 2σ(I)
R _int = 0.087

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.093
S = 1.12
2781 reflections
390 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.15 e Å⁻³
Δρ_min = −0.19 e Å⁻³
Absolute structure: determined from the synthesis

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and ORTEPIII (Burnett & Johnson, 1996 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812003674/ds2173sup1.cif

e-68-0o610-sup1.cif^{(39.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812003674/ds2173Isup2.hkl

e-68-0o610-Isup2.hkl^{(136.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812003674/ds2173Isup3.mol

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
N2—H2⋯N3	0.86	2.53	2.955 (4)	112
N4—H3⋯O5ⁱ	0.86	2.17	2.981 (5)	157

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The fungus Claviceps purpurea is distributed worldwide through various climatic zones and produces a broad range of ergot alkaloids on grasses and cereal grains during the growth process whereas six epimeric pairs are predominantly formed. One of these main ergot alkaloids is ergotaminine. Contamination of flour and cereal based foods with ergot alkaloids including ergotaminine has previously been reported (Crews et al., 2009; Müller et al., 2009). The biologically inactive C8-(S)-isomer ergotaminine (Pierri et al., 1982) can be converted to the biologically active C8-(R)-isomer ergotamine and vice versa (Komarova & Tolkachev, 2001). The molecule crystallizes in the monoclinic space group P2₁. 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)). The isomeric purity (98%) of ergotaminine was proved by HPLC-FLD.