PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2275.
Published online 2010 August 11. doi:  10.1107/S1600536810030825
PMCID: PMC3008012

Ergometrinine

Abstract

The absolute configuration of ergometrinine, C19H23N3O2 {systematic name: (6aR,9S)-N-[(S)-1-hy­droxy­propan-2-yl]-7-methyl-4,6,6a,7,8,9-hexa­hydro­indolo[4,3-fg]quinoline-9-carb­ox­amide}, was established based on epimerization reaction of ergometrine, which was followed by preparative HPLC. The non-aromatic ring (ring C of the ergoline skeleton) directly fused to the aromatic rings is nearly planar [maximum deviation = 0.271 (3) Å] and shows an envelope conformation, whereas ring D, involved in an intra­molecular N—H(...)N hydrogen bond, exibits a slightly distorted chair conformation. The structure displays undulating layers in the ac plane formed by O—H(...)O and N—H(...)O hydrogen bonds.

Related literature

Ergometrinine is one of the main ergot alkaloids produced by the fungus Claviceps purpurea on cereal grains in the field, see: Crews et al. (2009 [triangle]); Müller et al. (2009 [triangle]). For investigations of the biologically inactive C8-(S)-isomer of ergometrinine, see: Pierri et al. (1982 [triangle]); Komarova & Tolkachev (2001 [triangle]). For the crystal structure of ergometrine maleate, see: Cejka et al. (1996 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2275-scheme1.jpg

Experimental

Crystal data

  • C19H23N3O2
  • M r = 325.40
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2275-efi1.jpg
  • a = 7.4097 (5) Å
  • b = 12.7313 (7) Å
  • c = 18.2648 (9) Å
  • V = 1723.01 (17) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 0.66 mm−1
  • T = 298 K
  • 0.20 × 0.05 × 0.02 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971 [triangle]) T min = 0.879, T max = 0.986
  • 4023 measured reflections
  • 1889 independent reflections
  • 1269 reflections with I > 2σ(I)
  • R int = 0.056
  • 3 standard reflections every 60 min intensity decay: 2%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.044
  • wR(F 2) = 0.112
  • S = 1.00
  • 1889 reflections
  • 219 parameters
  • H-atom parameters constrained
  • Δρmax = 0.14 e Å−3
  • Δρmin = −0.16 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 [triangle]); program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810030825/sj5027sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810030825/sj5027Isup2.hkl

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

supplementary crystallographic information

Comment

Ergometrinine is one of the main ergot alkaloids produced by the fungus Claviceps purpurea on cereal grains in the field. Contamination of flour and cereal based foods with ergot alkaloids including ergometrinine has previously been reported (Crews et al., 2009, Müller et al., 2009). The biologically inactive C8-(S)-isomer ergometrinine (Pierri et al., 1982) can be converted to the biologically active C8-(R)-isomer ergometrine and vice versa (Komarova & Tolkachev, 2001). The molecule crystallizes in the orthorhombic space group P212121. 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 epimerization reaction of ergometrine, whose absolute configuration was determined previously (Cejka et al., 1996). Besides the intramolecular hydrogen bonds between N1-H1N and N2 (not shown in Fig. 2), each molecule is connected to four adjacent molecules via intermolecular hydrogen bonds (see dashed green bonds in Fig. 2). As a result undulating layers are formed in the the ac plane.

Experimental

Ergometrine maleate salt was purchased from Sigma-Aldrich (Taufkirchen, Germany). The isomeric purity (> 99%) of ergometrine was proved by HPLC-FLD. The stereoselective conversion of ergometrine to ergometrinine was carried out as follows: 40 mg of ergometrine maleate were placed in a 250 ml round-bottom flask, dissolved in 100 ml methanol and 4 ml 28% ammonium hydroxide solution was added. The resulting mixture was stored at 40 °C in a drying cabinet in darkness for epimerization reaction. After 4 days liquid chromatography showed two different compounds, the reactant ergometrine and the product ergometrinine. Afterwards the solvent was removed in vacuo and the residue of compounds was redissolved in a mixture of water and acetonitrile (70:30, v:v) and subjected to preparative HPLC for separation and purification of the two epimers. Colourless crystals of ergometrinine were grown by slow solvent evaporation from acetonitrile:water (80:20, v:v) in the absence of light at ambient temperature.

Refinement

In the absence of significant anomalous dispersion effects, Friedel pairs were merged.

The N—H and O—H hydrogen atoms were located in difference maps and and fixed in their found positions (AFIX 3) with Uiso(H) = 1.2 of the parent atom Ueq or 1.5 Ueq(Cmethyl, O).

Figures

Fig. 1.
: ORTEP representation of the title compound with atomic labeling shown with 30% probability displacement ellipsoids.
Fig. 2.
: View of the unit cell of the title compound along [100], showing the hydrogen-bonded layers stacked along the [001] direction. Hydrogen bonds are drawn as dashed lines.

Crystal data

C19H23N3O2F(000) = 696
Mr = 325.40Dx = 1.254 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 7.4097 (5) Åθ = 15–23°
b = 12.7313 (7) ŵ = 0.66 mm1
c = 18.2648 (9) ÅT = 298 K
V = 1723.01 (17) Å3Needle, yellow
Z = 40.20 × 0.05 × 0.02 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1269 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.056
graphiteθmax = 70.0°, θmin = 4.2°
ω/2θ scansh = −8→9
Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971)k = −15→15
Tmin = 0.879, Tmax = 0.986l = −22→22
4023 measured reflections3 standard reflections every 60 min
1889 independent reflections intensity decay: 2%

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.112H-atom parameters constrained
S = 1.00w = 1/[σ2(Fo2) + (0.0561P)2 + 0.0234P] where P = (Fo2 + 2Fc2)/3
1889 reflections(Δ/σ)max < 0.001
219 parametersΔρmax = 0.14 e Å3
0 restraintsΔρmin = −0.16 e Å3

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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.2918 (3)−0.17372 (18)0.36716 (13)0.0586 (7)
O20.7137 (5)−0.32052 (18)0.48938 (13)0.0815 (10)
H2O0.7329−0.31910.54390.122*
N10.5819 (4)−0.1255 (2)0.35374 (16)0.0550 (8)
H1N0.6603−0.07930.32590.066*
N20.6383 (4)0.06231 (19)0.26795 (14)0.0519 (8)
N30.7306 (5)0.4652 (2)0.43312 (17)0.0666 (9)
H3N0.73020.53720.44760.080*
C10.4047 (6)−0.1103 (2)0.34594 (17)0.0464 (9)
C20.6592 (5)−0.2226 (3)0.38200 (17)0.0520 (9)
H20.5736−0.27930.37150.062*
C30.6825 (6)−0.2176 (2)0.46383 (19)0.0602 (11)
H2A0.7839−0.17270.47610.072*
H2B0.5749−0.18890.48640.072*
C40.8315 (6)−0.2470 (4)0.3419 (2)0.0890 (15)
H4A0.8070−0.25300.29040.133*
H4B0.8802−0.31210.35960.133*
H4C0.9170−0.19160.35000.133*
C50.3492 (5)−0.0110 (2)0.30590 (17)0.0493 (9)
H50.2276−0.02280.28650.059*
C60.4692 (6)0.0159 (3)0.24169 (19)0.0584 (11)
H6A0.4950−0.04710.21370.070*
H6B0.40770.06530.20980.070*
C70.6047 (5)0.1676 (2)0.29911 (16)0.0440 (8)
H70.56540.21290.25880.053*
C80.7810 (5)0.2148 (3)0.32985 (19)0.0527 (9)
H8A0.83890.16440.36200.063*
H8B0.86310.23030.28990.063*
C90.7408 (5)0.3130 (2)0.37121 (18)0.0491 (9)
C100.8341 (6)0.4010 (3)0.3898 (2)0.0622 (10)
H100.95160.41570.37520.075*
C110.5652 (6)0.4189 (3)0.44279 (19)0.0543 (10)
C120.5701 (5)0.3240 (2)0.40378 (16)0.0435 (8)
C130.4242 (5)0.2560 (2)0.40020 (16)0.0436 (8)
C140.4491 (5)0.1623 (2)0.35402 (16)0.0417 (8)
C150.3382 (5)0.0807 (2)0.35753 (18)0.0459 (8)
H150.24950.08020.39360.055*
C160.2697 (5)0.2850 (3)0.43839 (18)0.0545 (9)
H160.16810.24210.43730.065*
C170.2672 (7)0.3792 (3)0.4786 (2)0.0685 (12)
H170.16310.39620.50450.082*
C180.4104 (7)0.4473 (3)0.4817 (2)0.0656 (11)
H180.40470.50940.50830.079*
C190.7721 (7)0.0655 (3)0.2083 (2)0.0793 (14)
H19A0.7780−0.00200.18500.119*
H19B0.88840.08300.22790.119*
H19C0.73710.11750.17300.119*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0606 (17)0.0495 (13)0.0658 (15)−0.0125 (13)0.0060 (14)0.0047 (12)
O20.129 (3)0.0458 (13)0.0695 (17)0.0021 (17)−0.0340 (18)0.0006 (12)
N10.048 (2)0.0480 (16)0.0684 (19)−0.0048 (15)−0.0015 (17)0.0171 (14)
N20.067 (2)0.0411 (14)0.0477 (15)0.0007 (15)0.0157 (16)−0.0004 (12)
N30.090 (3)0.0410 (15)0.0693 (19)−0.0083 (18)−0.017 (2)−0.0049 (15)
C10.054 (3)0.0427 (17)0.0426 (17)−0.0070 (19)0.0016 (18)−0.0021 (14)
C20.054 (2)0.0444 (18)0.058 (2)−0.0008 (18)−0.0048 (19)0.0014 (16)
C30.071 (3)0.0408 (18)0.069 (2)−0.0040 (19)−0.017 (2)0.0001 (16)
C40.069 (3)0.094 (3)0.104 (4)0.013 (3)0.018 (3)0.011 (3)
C50.051 (2)0.0449 (17)0.0523 (19)−0.0076 (18)−0.0095 (18)0.0020 (15)
C60.084 (3)0.0473 (19)0.0442 (18)0.000 (2)−0.005 (2)−0.0034 (16)
C70.050 (2)0.0414 (15)0.0408 (16)0.0026 (17)0.0039 (17)0.0042 (14)
C80.046 (2)0.0538 (19)0.058 (2)−0.0014 (18)0.0112 (18)0.0019 (16)
C90.051 (2)0.0431 (18)0.0531 (19)−0.0019 (17)−0.0028 (19)0.0044 (15)
C100.059 (3)0.054 (2)0.074 (2)−0.007 (2)−0.008 (2)0.0077 (19)
C110.072 (3)0.0394 (17)0.0520 (19)0.0029 (19)−0.010 (2)0.0001 (16)
C120.052 (2)0.0381 (16)0.0408 (17)0.0039 (18)−0.0029 (17)0.0020 (14)
C130.049 (2)0.0412 (16)0.0409 (16)0.0084 (18)0.0016 (17)0.0048 (13)
C140.048 (2)0.0368 (15)0.0406 (16)0.0042 (16)−0.0001 (16)0.0035 (13)
C150.046 (2)0.0443 (16)0.0476 (17)0.0042 (17)0.0016 (17)0.0024 (14)
C160.058 (3)0.0512 (18)0.0541 (19)0.0053 (19)0.010 (2)0.0019 (17)
C170.087 (3)0.060 (2)0.059 (2)0.021 (3)0.018 (2)−0.0003 (19)
C180.098 (3)0.0418 (18)0.057 (2)0.018 (2)0.004 (2)−0.0066 (16)
C190.104 (4)0.061 (2)0.073 (2)0.004 (3)0.042 (3)−0.0040 (19)

Geometric parameters (Å, °)

O1—C11.226 (4)C6—H6B0.9700
O2—C31.410 (4)C7—C141.530 (4)
O2—H2O1.0068C7—C81.544 (5)
N1—C11.334 (5)C7—H70.9800
N1—C21.457 (4)C8—C91.490 (5)
N1—H1N0.9707C8—H8A0.9700
N2—C61.466 (5)C8—H8B0.9700
N2—C191.474 (5)C9—C101.360 (5)
N2—C71.477 (4)C9—C121.405 (5)
N3—C111.371 (5)C10—H100.9300
N3—C101.372 (5)C11—C181.397 (6)
N3—H3N0.9537C11—C121.403 (4)
C1—C51.517 (4)C12—C131.386 (5)
C2—C41.505 (5)C13—C161.391 (5)
C2—C31.506 (5)C13—C141.473 (4)
C2—H20.9800C14—C151.325 (4)
C3—H2A0.9700C15—H150.9300
C3—H2B0.9700C16—C171.407 (5)
C4—H4A0.9600C16—H160.9300
C4—H4B0.9600C17—C181.371 (6)
C4—H4C0.9600C17—H170.9300
C5—C151.503 (4)C18—H180.9300
C5—C61.511 (5)C19—H19A0.9600
C5—H50.9800C19—H19B0.9600
C6—H6A0.9700C19—H19C0.9600
C3—O2—H2O109.5N2—C7—H7107.2
C1—N1—C2123.2 (3)C14—C7—H7107.2
C1—N1—H1N116.4C8—C7—H7107.2
C2—N1—H1N117.7C9—C8—C7110.0 (3)
C6—N2—C19110.1 (3)C9—C8—H8A109.7
C6—N2—C7110.3 (3)C7—C8—H8A109.7
C19—N2—C7111.9 (3)C9—C8—H8B109.7
C11—N3—C10108.5 (3)C7—C8—H8B109.7
C11—N3—H3N112.1H8A—C8—H8B108.2
C10—N3—H3N137.2C10—C9—C12105.6 (3)
O1—C1—N1122.8 (3)C10—C9—C8135.7 (4)
O1—C1—C5121.1 (3)C12—C9—C8118.6 (3)
N1—C1—C5116.1 (3)C9—C10—N3110.5 (4)
N1—C2—C4109.6 (3)C9—C10—H10124.7
N1—C2—C3111.1 (3)N3—C10—H10124.7
C4—C2—C3113.3 (4)N3—C11—C18133.5 (3)
N1—C2—H2107.5N3—C11—C12106.4 (3)
C4—C2—H2107.5C18—C11—C12120.1 (4)
C3—C2—H2107.5C13—C12—C11122.8 (3)
O2—C3—C2107.9 (3)C13—C12—C9128.3 (3)
O2—C3—H2A110.1C11—C12—C9108.9 (3)
C2—C3—H2A110.1C12—C13—C16116.9 (3)
O2—C3—H2B110.1C12—C13—C14115.8 (3)
C2—C3—H2B110.1C16—C13—C14127.2 (3)
H2A—C3—H2B108.4C15—C14—C13122.0 (3)
C2—C4—H4A109.5C15—C14—C7122.3 (3)
C2—C4—H4B109.5C13—C14—C7115.7 (3)
H4A—C4—H4B109.5C14—C15—C5123.0 (3)
C2—C4—H4C109.5C14—C15—H15118.5
H4A—C4—H4C109.5C5—C15—H15118.5
H4B—C4—H4C109.5C13—C16—C17119.9 (4)
C15—C5—C6110.0 (3)C13—C16—H16120.0
C15—C5—C1111.1 (2)C17—C16—H16120.0
C6—C5—C1113.8 (3)C18—C17—C16123.4 (4)
C15—C5—H5107.2C18—C17—H17118.3
C6—C5—H5107.2C16—C17—H17118.3
C1—C5—H5107.2C17—C18—C11116.8 (3)
N2—C6—C5109.9 (3)C17—C18—H18121.6
N2—C6—H6A109.7C11—C18—H18121.6
C5—C6—H6A109.7N2—C19—H19A109.5
N2—C6—H6B109.7N2—C19—H19B109.5
C5—C6—H6B109.7H19A—C19—H19B109.5
H6A—C6—H6B108.2N2—C19—H19C109.5
N2—C7—C14109.8 (2)H19A—C19—H19C109.5
N2—C7—C8110.5 (3)H19B—C19—H19C109.5
C14—C7—C8114.6 (2)
C2—N1—C1—O15.7 (5)N3—C11—C12—C90.7 (4)
C2—N1—C1—C5−171.7 (3)C18—C11—C12—C9−178.6 (3)
C1—N1—C2—C4142.9 (4)C10—C9—C12—C13178.9 (3)
C1—N1—C2—C3−91.1 (4)C8—C9—C12—C13−3.3 (5)
N1—C2—C3—O2165.5 (3)C10—C9—C12—C11−1.0 (4)
C4—C2—C3—O2−70.6 (4)C8—C9—C12—C11176.9 (3)
O1—C1—C5—C1596.5 (4)C11—C12—C13—C16−0.9 (5)
N1—C1—C5—C15−86.0 (4)C9—C12—C13—C16179.3 (3)
O1—C1—C5—C6−138.6 (3)C11—C12—C13—C14177.2 (3)
N1—C1—C5—C638.8 (4)C9—C12—C13—C14−2.6 (5)
C19—N2—C6—C5166.6 (3)C12—C13—C14—C15165.5 (3)
C7—N2—C6—C5−69.4 (3)C16—C13—C14—C15−16.6 (5)
C15—C5—C6—N248.3 (4)C12—C13—C14—C7−17.5 (4)
C1—C5—C6—N2−77.1 (3)C16—C13—C14—C7160.3 (3)
C6—N2—C7—C1450.1 (3)N2—C7—C14—C15−14.9 (4)
C19—N2—C7—C14173.1 (3)C8—C7—C14—C15−140.1 (3)
C6—N2—C7—C8177.6 (3)N2—C7—C14—C13168.2 (3)
C19—N2—C7—C8−59.4 (4)C8—C7—C14—C1343.0 (4)
N2—C7—C8—C9−171.3 (2)C13—C14—C15—C5173.7 (3)
C14—C7—C8—C9−46.5 (4)C7—C14—C15—C5−3.1 (5)
C7—C8—C9—C10−155.5 (4)C6—C5—C15—C14−13.5 (5)
C7—C8—C9—C1227.4 (4)C1—C5—C15—C14113.5 (4)
C12—C9—C10—N30.9 (4)C12—C13—C16—C17−0.5 (5)
C8—C9—C10—N3−176.4 (4)C14—C13—C16—C17−178.3 (3)
C11—N3—C10—C9−0.5 (4)C13—C16—C17—C181.2 (5)
C10—N3—C11—C18179.1 (4)C16—C17—C18—C11−0.6 (6)
C10—N3—C11—C12−0.2 (4)N3—C11—C18—C17−179.9 (4)
N3—C11—C12—C13−179.1 (3)C12—C11—C18—C17−0.7 (5)
C18—C11—C12—C131.5 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1N···N20.972.102.890 (4)138.
O2—H2O···O1i1.011.682.684 (3)172.
N3—H3N···O2ii0.951.972.918 (4)173.

Symmetry codes: (i) x+1/2, −y−1/2, −z+1; (ii) x, y+1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ5027).

References

  • Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst.32, 115–119.
  • Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.
  • Cejka, J., Husak, M., Kratochvil, B., Jegorov, A. & Cvak, L. (1996). Collect. Czech. Chem. Commun.61, 1396–1404.
  • Crews, C., Anderson, W. A. C., Rees, G. & Krska, R. (2009). Food Addit. Contam. Part B Surveill.2, 79–85. [PubMed]
  • Dräger, M. & Gattow, G. (1971). Acta Chem. Scand.25, 761–762.
  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Komarova, E. L. & Tolkachev, O. N. (2001). Pharm. Chem. J.35, 37–45.
  • Müller, C., Kemmlein, S., Klaffke, H., Krauthause, W., Preiss-Weigert, A. & Wittkowski, R. (2009). Mol. Nutr. Food Res.53, 500–507. [PubMed]
  • Pierri, L., Pitman, I. H., Rae, I. D., Winkler, D. A. & Andrews, P. R. (1982). J. Med. Chem.25, 937–942. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography