Crystal structure of anagyrine perchlorate

Kambarali K Turgunov; Shukhrat B Rakhimov; Valentina I Vinogradova; Bakhodir Tashkhodjaev

doi:10.1107/S2056989015007781

. 2015 Apr 25;71(Pt 5):o343–o344. doi: 10.1107/S2056989015007781

Crystal structure of anagyrine perchlorate

Kambarali K Turgunov ^a,^*, Shukhrat B Rakhimov ^a, Valentina I Vinogradova ^a, Bakhodir Tashkhodjaev ^a

PMCID: PMC4420039 PMID: 25995939

Abstract

The title molecular salt, C₁₅H₂₁N₂O⁺·ClO₄ ⁻, crystallizes with four cations (A, B, C and D) and four anions in the chiral unit cell (space group P2₁). The alkaloid was isolated from the aerial parts of Genista Hispanica collected in the Samarkand region of Uzbekistan. Each cation is protonated at the N atom that bridges the alkaloid rings C and D. In each cation, ring A is almost planar and ring B adops a sofa conformation with the methylene group bridging to the C ring as the flap. Rings C and D adopt chair conformations with a cis ring junction in all four cations. In the crystal, A+B and C+D dimeric pairs linked by pairs of N—H⋯O hydrogen bonds are observed, which generate R ₂ ²(16) loops in each case. The dimers are consolidated by weak aromatic π–π stacking interactions between the A rings [centroid–centroid distances = 3.913 (3) and 3.915 (3) Å].

Keywords: crystal structure, alkaloid, Genista Hispanica, anagyrine, perchlorate, N—H⋯O hydrogen bonds, π–π stacking interactions

Related literature

For the isolation of the title alkaloid, see: Orechoff et al. (1934 ▸); Sagen et al. (2002 ▸). For NMR spectra of the title alkaloid, see: Sagen et al. (2002 ▸). For theoretical studies of anagyrine and the crystal structure of anagyrine hydrochloride monohydrate, see: Galasso et al. (2006 ▸). For a related crystal structure, see: Atta-ur-Rahman et al. (1991 ▸). graphic file with name e-71-0o343-scheme1.jpg

Experimental

Crystal data

C₁₅H₂₁N₂O⁺·ClO₄ ⁻
M _r = 344.79
Monoclinic,
a = 7.3550 (3) Å
b = 32.982 (1) Å
c = 12.8849 (4) Å
β = 90.709 (3)°
V = 3125.41 (19) Å³
Z = 8
Cu Kα radiation
μ = 2.42 mm⁻¹
T = 290 K
0.65 × 0.15 × 0.04 mm

Data collection

Oxford Diffraction Xcalibur Ruby diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 ▸) T _min = 0.651, T _max = 1.000
53652 measured reflections
12780 independent reflections
9677 reflections with I > 2σ(I)
R _int = 0.105

Refinement

R[F ² > 2σ(F ²)] = 0.064
wR(F ²) = 0.189
S = 1.02
12780 reflections
846 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.60 e Å⁻³
Δρ_min = −0.37 e Å⁻³
Absolute structure: Flack x determined using 3107 quotients [(I ⁺)−(I ⁻)]/[(I ⁺)+(I ⁻)] (Parsons et al., 2013 ▸)
Absolute structure parameter: −0.024 (12)

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 ▸); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▸); software used to prepare material for publication: publCIF (Westrip, 2010 ▸).

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S2056989015007781/hb7409sup1.cif

e-71-0o343-sup1.cif^{(61.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015007781/hb7409Isup2.hkl

e-71-0o343-Isup2.hkl^{(624.7KB, hkl)}

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S2056989015007781/hb7409fig1.tif

The molecular structure of cation A of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Click here for additional data file.^{(1.1MB, tif)}

. DOI: 10.1107/S2056989015007781/hb7409fig2.tif

Hydrogen bonding between molecules.

CCDC reference: 1060546

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N2AH2ANO1B	1.03(5)	1.91(6)	2.741(6)	136(5)
N2BH2CNO1A	0.77(7)	2.00(6)	2.742(5)	163(6)
N2CH2ENO1D ⁱ	0.90(9)	2.00(9)	2.735(6)	138(8)
N2DH2GNO1C ⁱⁱ	1.05(5)	1.74(5)	2.754(5)	159(5)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We thank the Academy of Sciences of the Republic of Uzbekistan for supporting this study (grant FA-F7-T185)

supplementary crystallographic information

S1. Comment

Quinolizidine alkaloids attracted the attention of researchers due to the structural characteristics and pharmacological activity. We have studied the aerial parts of Genista Hispanica collected in Samarkand region and isolated anagyrine with R_f 0.5 (chloroform-methanol 6:1) along with other alkaloids. Anagyrine a toxic alkaloid found in several species of Lupinus in the western United States. Acute poisoning produces nervousness, depression, loss of muscular control, convulsions, and coma.

Anagyrine perchlorate crystallizes in the monoclinic space group P2₁ with a long unique b-axis of 32.982 (1) Å .The asymmetric unit consist of four protonated anagyrine molecules and four perchlorate anions. The molecular structure of the alkaloid is shown in Fig. 1. The alkaloid molecule consists of four fused rings - planar ring A fused with the sofa ring B, and a twin-chair C/D fragment where C/D junction is cis. Conformation of all undependent molecules matches. Anagyrine molecule has three asymmetric centers at C6, C8, C10 and in addition by protonation of N2 it becomes as asymmetric senter. Configuration of chiral atoms are C-6R,C-8R,C-10R and N-2S. Crystal structure of thermopsine - a C-10-epimer of anagyrine was investigated by Atta-ur-Rahman et al. (1991).

In the crystal, pairs of hydrogen bonds between protonated N atom of the base and the carbonyl O atom link molecules to form two molecular associates (Fig.2, Table 1.). In addition the associates are linked by weak π–π stacking interactions observed between aromatic rings of molecule [centroid—centroid distance = 3.913 (3) Å and 3.915 (3) Å for undependent molecular pairs ]

S2. Experimental

S2.1. Synthesis and crystallization

The powdered air-dried plant material were extracted with 80% ethanol. After distilling off the alcohol, the residue was acidified with H₂SO₄ and washed with chloroform, then the extract was basified with 25% aqueous ammonia, the sum of alkaloids (8.81 g) were extracted with chloroform. The resulting sum were dissolved in ethanol and acidified with HNO₃ to a weakly acidic medium, precipitated cytisine nitrate crystals (0.98g) were separated, and the mother liquor was evaporated. The resulting aqueous residue was basified with 25% aqueous ammonia and alkaloids was extracted with chloroform. The resulting sum of alkaloids was subjected to column chromatography on silica gel eluting with chloroform-methanol (100: 1) and isolated anagyrine (0.16g). Obtained anagyrine was dissolved in acetone and perchloric acid was added until acidic medium of pH 5-6. Precipitated anagyrine perchlorate crystals were crystallized from methanol with m.p. 315 °C. Colourless prisms were obtained by re-crystallization from water at 50 °C .

S2.2. Refinement

Carbon-bound H atoms were placed geometrically and treated as riding on their parent atoms, with C—H distances of 0.93 Å (aromatic), 0.97 Å (methylen), 0.98 Å (tertiary carbon) and were refined with Uiso(H)=1.2Ueq(C) for all hydrogen atoms. N-bound H atoms involved in the intermolecular hydrogen bonding were found by difference Fourier synthesis and refined isotropically [N2A—H = 1.03 (5)Å, N2B—H 0.77 (7) Å, N2C—H 0.90 (9) Å, N2D—H 1.05 (5) Å].