N-Methyl­isosalsoline from Hammada scoparia

Raoudha Mezghani Jarraya; Amira Bouaziz; Besma Hamdi; Abdelhamid Ben Salah; Mohamed Damak

doi:10.1107/S160053680802477X

. 2008 Aug 6;64(Pt 9):o1714. doi: 10.1107/S160053680802477X

N-Methylisosalsoline from Hammada scoparia

Raoudha Mezghani Jarraya ^a, Amira Bouaziz ^a, Besma Hamdi ^b, Abdelhamid Ben Salah ^b, Mohamed Damak ^a,^*

PMCID: PMC2960642 PMID: 21201700

Abstract

The title compound (systematic name: 1,2-dimethyl-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol), C₁₂H₁₇NO₂, is a major alkaloid isolated from Hammada scoparia leaves. It belongs to the isoquinoline family and it was characterized by NMR spectroscopy and X-ray crystallographic techniques. The absolute configuration could not be reliably determined. An intermolecular O—H⋯N hydrogen bond is present in the crystal structure.

Related literature

For related literature on Hammada scoparia and isoquinoline alkaloids, see: Baker (1996 ▶); Benkrief et al. (1990 ▶); Carling & Sandberg (1970 ▶); El-Shazly & Wink (2003 ▶); El-Shazly et al. (2005 ▶); Iwasa et al. (2001 ▶); Jarraya & Damak (2001 ▶); Vetulani et al. (2001 ▶, 2003 ▶).

Experimental

Crystal data

C₁₂H₁₇NO₂
M _r = 207.27
Orthorhombic,
a = 7.5942 (6) Å
b = 10.8082 (8) Å
c = 13.2716 (10) Å
V = 1089.33 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 200 (2) K
0.48 × 0.37 × 0.22 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (Becker & Coppens, 1974 ▶) T _min = 0.961, T _max = 0.988
23859 measured reflections
3132 independent reflections
2870 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.089
S = 1.06
3132 reflections
136 parameters
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1998 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680802477X/zl2131sup1.cif

e-64-o1714-sup1.cif^{(17.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680802477X/zl2131Isup2.hkl

e-64-o1714-Isup2.hkl^{(150.6KB, 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
O2—H2⋯N1ⁱ	0.84	1.90	2.6970 (10)	159

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors gratefully acknowledge Professor Jean-Claude Daran (Directeur de Recherche, Laboratoire de Chimie de Coordination, CNRS–Toulouse) for helpful comments regarding this paper.

supplementary crystallographic information

Comment

Hammada scoparia has been reported to contain the alkaloids carnegine and N-methylisosalsoline as major tetrahydroisoquinoline alkaloids in addition to other minor alkaloids (Benkrief et al., 1990, Jarraya & Damak 2001; El-Shazly & Wink, 2003).

The tetrahydroisoquinoline alkaloids affect the vegetative nervous system (Vetulani et al., 2001 and 2003). Some of these alkaloids are known to be strong agonists at nicotinic acetylcholine receptors and it is thus likely that they serve as chemical defense compounds against insects and mammalian herbivores (El-Shazly et al., 2005). Other simple isoquinoline alkaloids display potent, and often selective cytotoxicity or exhibit potential antimicrobial, antimalarial, antiviral and anti-HIV activities (Baker, 1996; Iwasa et al., 2001).

The current study describes the isolation and the structure elucidation of N-methylisosalsoline. The structure of the title compound was established principally by two-dimensional NMR spectroscopy and through X-ray diffraction analysis although the absolute configuration could not be reliably determined.

The conformation of this compound is stabilized by an intermolecular hydrogen bond between the hydroxyl O₂—H₂ group and atom N₁ (Table 1). The molecules are assembled by intermolecular O—H···N hydrogen bonds (Table 1, Fig. 2)

Experimental

The title compound was extracted from Hammada scoparia leaves:

Plant material Hammada scoparia (Pomel) Iljin= (Haloxylon scoparium (Pomel) Bge. = Haloxylon articulatum ssp scorparium (Pomel) Batt. = Arthrophytum scoparium (Pomel) Iljin), belongs to Chenopodiaceae family and is locally known as "rimth" in Sfax, Tunisia.

Leaves were carefully detached from the fresh plant, collected in June 2007 in Sfax, Tunisia, and air-dried. Voucher specimens (LCSN101) have been deposited at the " Laboratoire de Chimie des Substances Naturelles", Faculty of Science, University of Sfax, Tunisia.

Extraction and isolation of the N-Methylisosalsoline from Hammada scoparia leaves:

Air-dried leaves of Hammada scoparia were extracted at room temperature during 48 h with a mixture (EtOH-H₂O, 1–9, v-v). After filtration through folder filter paper Whatman N° 1, the ethanol was removed under reduced pressure and the remaining aqueous phase was acidified with HCl (pH = 3) and then defatted by extraction with CH₂Cl₂. The defatted mother liquor was made alkaline with an NH₄OH solution (pH = 10) and immediately extracted with CH₂Cl₂ to exhaustion. The latter CH₂Cl₂ extract was concentrated to yield a reddish-brown residue (total alkaloids).

The total Alkaloids (5 g) were separated, on column chromatography over silica gel 60 (0.063–0.200 mm; 160 g), using a gradient of dichloromethane-methanol as eluents. Eleven fractions were isolated according to their similarity by thin layer chromatography analyses. Further purifications gave two major pure alkaloids; the first is oily: Carnegine (1050 mg; fraction 3 eluted with dichloromethane) and the second (white rosette crystals) is N-methylisosalsoline (545 mg; fraction 7 eluted with dichloromethane-methanol, 94–6, v-v). These alkaloids were previously isolated from Hammada scoparia (Carling & Sandberg, 1970; Benkrief et al., 1990; Jarraya & Damak, 2001; El-Shazly & Wink, 2003). Their structures were determined on the basis of their spectral data such as UV, MS, ¹H NMR and H—H COSY, ¹³C NMR (BB, DEPT and C—H COSY, HMQC, HMBC, NOESY) and confirmed by comparison with published spectra.

N-Methylisosalsoline (1-Methylcorypalline), white rosette crystals (MeOH), mp 443 K, UV λ_max (EtOH) nm = 207, 225, 285. λ_max (EtOH + OH^-) nm = 213, 245, 300. EIMS, m/z (rel. int.): [M⁺] 207 (15), 193 (30), 192 (100), 177 (45), 164 (10), 149 (15), 121 (5), 96 (6), 91 (5), 77 (5), 57 (5), 42 (4). IR: (CHCl₃) ν_max (cm^-1): 3540, 2950, 2850, 2800, 1600, 1520.

Spectroscopic analysis, ¹H NMR (300 MHz, CDCl₃, p.p.m.): 1.34 (3H, d, J = 6.6 Hz, CH₃–C₁); 2.45 (3H, s, CH₃–N); 2.63 (1H, ddd, J = 11.4, 6.9, 5.1 Hz, H–C₃); 2.77 (2H, m, 2 H–C₄); 3.02 (1H, ddd, J = 11.4, 6.9, 5.1 Hz,H–C₃); 3.49 (1H, q, J = 6.6 Hz, H–C₁); 3.83 (3H, s, CH₃–O); 6.53 (1H,s, aromatic H, H–C₅); 6.63 (1H, s, aromatic H, H–C₈).

¹³C NMR (75.5 MHz, CDCl₃, p.p.m.): 58.51, C₁; 48.94, C₃; 27.36, C₄; 124.84, C_4a; 112.96, C₅; 145.31, C₆; 144.00, C₇; 110.57, C₈; 131.95, C_8a; 19.45, CH₃–C₁; 42.70, CH₃–N; 55.77, CH₃–O. The HMQC spectra showed correlations between 112.96 (C₅) and 6.53 (1H, s,aromatic H, H–C₅); 110.57 (C₈) and 6.63 (1H, s, aromatic H, H–C₈).

Suitable white X-ray quality crystals of this compound were obtained by recrystallization from methanol.