3-Hydr­oxy-1,2,3,9-tetra­hydro­pyrrolo[2,1-b]quinazolin-4-ium chloride dihydrate: (+)-vasicinol hydro­chloride dihydrate from Peganum harmala L

Amir Muhammad Khan; Ghulam Abbas; Rizwana Aleem Qureshi; Uzma Khan; Muhammad Asad Ghufran; Helen Stoeckli-Evans

doi:10.1107/S1600536809003766

. 2009 Feb 6;65(Pt 3):o474–o475. doi: 10.1107/S1600536809003766

3-Hydroxy-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-4-ium chloride dihydrate: (+)-vasicinol hydrochloride dihydrate from Peganum harmala L

Amir Muhammad Khan ^a, Ghulam Abbas ^b, Rizwana Aleem Qureshi ^a,^*, Uzma Khan ^a, Muhammad Asad Ghufran ^a, Helen Stoeckli-Evans ^c

PMCID: PMC2968537 PMID: 21582144

Abstract

The title compound, C₁₁H₁₃N₂O⁺·Cl⁻·2H₂O, the dihydrate of (+)-vasicinol hydrochloride, is a pyrrolidinoquinazoline alkaloid. It was isolated from the ethyl acetate fraction of the leaves of Peganum harmala L. The pyrrolidine ring has an envelope conformation with the C atom at position 2 acting as the flap and the C atom at position 3, carrying the hydroxyl substituent, has an S configuration. The absolute configuration was determined as a result of the anomalous scattering of the Cl atom. In the crystal structure, molecules stack along the a axis, connected to one another via intermolecular O—H⋯Cl and N—H⋯Cl hydrogen bonds, forming approximately triangular-shaped R ₂ ¹(7) rings, and O—H⋯Cl and O—H⋯O hydrogen bonds, forming pentagonal-shaped R ₅ ⁴(10) rings. The overall effect is a ribbon-like arrangement running parallel to the a axis.

Related literature

For the isolation (+)-vasicinol and the crystal structure analysis of (+)-vasicinol hydrobromide, see: Joshi et al. (1996 ▶). For general background on pyrrolidino-quinazoline alkaloids and their structures, see: Szulzewsky et al. (1976 ▶): Openshaw (1953 ▶); Bailey (1986 ▶); Rizk (1986 ▶); Tashkhodzhaev et al. (1995 ▶); Turgunov et al. (1995 ▶). For a study on the anti-Leishmaniasis activity of (+)-vasicinol hydrochloride dihydrate, see: Misra et al. (2008 ▶). For further related literature on natural products, see: Hilal & Youngken (1983 ▶); Mirzakhmedov et al. (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₁H₁₃N₂O⁺·Cl⁻·2H₂O
M _r = 260.72
Orthorhombic,
a = 7.0386 (6) Å
b = 9.5752 (10) Å
c = 18.4041 (18) Å
V = 1240.4 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.31 mm⁻¹
T = 173 (2) K
0.42 × 0.19 × 0.11 mm

Data collection

Stoe IPDS diffractometer
Absorption correction: none
8680 measured reflections
2422 independent reflections
1834 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.061
S = 0.90
2422 reflections
216 parameters
2 restraints
All H-atom parameters refined
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ▶), 984 Friedel pairs
Flack parameter: 0.004 (64)

Data collection: EXPOSE in IPDS-I (Stoe & Cie, 2000 ▶); cell refinement: CELL in IPDS-I; data reduction: INTEGRATE in IPDS-I; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809003766/lh2765sup1.cif

e-65-0o474-sup1.cif^{(18.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809003766/lh2765Isup2.hkl

e-65-0o474-Isup2.hkl^{(119KB, hkl)}

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
O1—H1O⋯Cl1ⁱ	0.90 (2)	2.20 (2)	3.086 (2)	171 (2)
N9—H9N⋯Cl1ⁱ	0.83 (2)	2.35 (2)	3.155 (2)	167 (2)
O1W—H1WA⋯Cl1ⁱⁱ	0.83 (4)	2.39 (4)	3.204 (2)	167 (3)
O1W—H1WB⋯O2Wⁱⁱ	0.79 (4)	1.96 (4)	2.720 (3)	162 (4)
O2W—H2WA⋯Cl1ⁱⁱⁱ	0.83 (4)	2.35 (4)	3.173 (2)	175 (3)
O2W—H2WB⋯O1W^iv	0.89 (3)	1.83 (3)	2.718 (3)	179 (5)

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

supplementary crystallographic information

Comment

Peganum harmala L is a member of the family Zygophyllaceae (Hilal and Youngken, 1983). This plant is commonly distributed in the Attock District, Islamabad, including the Margalla Hills. Several alkaloids have been isolated from the seeds and roots of this plant and have been identified as chemicals with a β-carboline structure, such as harmine, harmaline, harmalol, and harman (Bailey, 1986; Rizk, 1986), or with a quinazoline structure, such as vasicine and vasicinon (Openshaw, 1953; Bailey, 1986; Joshi et al., 1996). Here we report on the crystal structure of the title compound, the dihydrate of (+)Vasicinol hydrochloride. It is a pyrrolidino-quinazoline alkaloid and was isolated from the ethylacetate fraction of the leaves of Peganum harmala L, collected from the Margalla Hills, Islamabad.

The molecular structure of the title compound is shown in Fig. 1. Dimensions are similar to those observed in other pyrrolidino-quinazoline alkaloids (Joshi et al., 1996; Tashkhodzhaev et al., 1995; Turgunov et al., 1995; Szulzewsky et al., 1976). The title compound crystallizes in the non-centrosymmetric orthorhombic space group P2₁2₁2₁. The crystal structure of (+)-Vasicinol hydrobromide has been reported previously (Joshi et al., 1996), and crystallizes in the non-centrosymmetric monoclinic space group P2₁, with two independent molecules per asymmetric unit.

The pyrrolidine ring has an envelope conformation on atom C2; the puckering parameters (Cremer & Pople, 1975) are Q(2) = 0.243 (2) Å, and φ(2) = 253.8 (5)°. The carbon atom carrying the hydroxyl substituent, atom C3, has a S-configuration. The absolute configuration of the title compound was determined as a result of the anomalous scattering of the Cl-atom.

In the crystal the molecules stacks up the a axis and are connected to one another via a series of O—H···Cl, N—H···Cl hydrogen bonds, with approximately triangular-shaped R¹₂(7) rings (Bernstein et al., 1995) and O—H···Cl and O—H···O hydrogen bonds, forming pentagonal-shaped R₅⁴(10) rings [see Fig. 2 and Table 1]. In this way a ribon-like arrangement is formed running parallel to the a axis. The same triangular arrangement, involving O—H···halide^- and N—H···halide^- hydrogen bonds, is also observed in the crystal packing of (+)-Vasicine hydrobromide (Fig. 3; Joshi et al., 1996).

Experimental

Peganum harmala L is a member of the family Zygophyllaceae (Hilal & Youngken, 1983). This plant is commonly distributed in the Attock District, Islamabad, including the Margalla Hills, Gilgit: Chilas, Yasin, Gupis, Phunder, Hunza, Skardu. The leaves of the plant were collected from the Margalla Hills, Islamabad and the sample was deposited in the herbarium of Quaid-i-Azam University (ISL) under the accession No. 123774 and 123775. The air dried leaves were powdered and extracted three times with methanol. The extracts were and concentrated to a semi-solid mass. Water was added to this semi-solid mass to form a paste. The extract was then fractioned using different solvents according to their increasing polarity. The title compound was isolated from the ethylacetate fraction of the leaves of Peganum harmala L as colourless rod-like crystals.