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Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1714.
Published online 2008 August 6. doi:  10.1107/S160053680802477X
PMCID: PMC2960642

N-Methyl­isosalsoline from Hammada scoparia

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 [triangle]); Benkrief et al. (1990 [triangle]); Carling & Sandberg (1970 [triangle]); El-Shazly & Wink (2003 [triangle]); El-Shazly et al. (2005 [triangle]); Iwasa et al. (2001 [triangle]); Jarraya & Damak (2001 [triangle]); Vetulani et al. (2001 [triangle], 2003 [triangle]).

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Object name is e-64-o1714-scheme1.jpg

Experimental

Crystal data

  • C12H17NO2
  • M r = 207.27
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1714-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.44 e Å−3
  • Δρmin = −0.24 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

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

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 λmax (EtOH) nm = 207, 225, 285. λmax (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) νmax (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, C4a; 112.96, C5; 145.31, C6; 144.00, C7; 110.57, C8; 131.95, C8a; 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.

Refinement

All H atoms attached to C atoms and O atom were fixed geometrically and treated as riding with C—H = 0.98 Å (Cmethine), 0.97 Å (Cmethylene), 0.96Å (Cmethyl), 0.93Å (Caromatic) and O—H = 0.84 Å with Uiso(H) = 1.2Ueq(Cmethylene, Cmethine, Caromatic) or Uiso(H) = 1.5Ueq (Cmethyl, O).

In the absence of significant anomalous scattering, the absolute configuration could not be reliably determined and then the Friedel pairs were merged and any references to the Flack parameter were removed.

Figures

Fig. 1.
Molecular view of the title compound with the atom-labelling scheme. Ellispsoids are drawn at the 50% probability level. H atoms are represented as spheres of arbitrary radii.
Fig. 2.
Partial packing view showing the formation of pseudo dimer through O—H···N hydrogen bonds. Hydrogen bonds are shown as dashed lines.

Crystal data

C12H17NO2Dx = 1.264 Mg m3
Mr = 207.27Melting point: 473 K
Orthorhombic, P212121Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2100 reflections
a = 7.5942 (6) Åθ = 2.7–21.3º
b = 10.8082 (8) ŵ = 0.09 mm1
c = 13.2716 (10) ÅT = 200 (2) K
V = 1089.33 (14) Å3Prism, colourless
Z = 40.48 × 0.37 × 0.22 mm
F000 = 448

Data collection

Bruker SMART CCD area-detector diffractometer3132 independent reflections
Radiation source: sealed tube2870 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.030
T = 200(2) Kθmax = 37.1º
[var phi] and ω scansθmin = 2.4º
Absorption correction: multi-scan(Becker & Coppens, 1974)h = −12→10
Tmin = 0.961, Tmax = 0.988k = −18→18
23859 measured reflectionsl = −22→22

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.033H-atom parameters constrained
wR(F2) = 0.089  w = 1/[σ2(Fo2) + (0.0579P)2 + 0.028P] where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max = 0.001
3132 reflectionsΔρmax = 0.44 e Å3
136 parametersΔρmin = −0.24 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

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
C10.05540 (10)0.85207 (7)0.13064 (6)0.01206 (13)
H10.04220.90130.06730.014*
C30.25806 (11)0.83001 (8)0.27194 (6)0.01586 (14)
H3A0.15570.80260.31240.019*
H3B0.33860.87660.31670.019*
C40.35296 (11)0.71807 (8)0.22912 (6)0.01475 (14)
H4A0.46940.74370.20290.018*
H4B0.37250.65670.28340.018*
C4A0.24733 (10)0.65931 (7)0.14534 (6)0.01156 (13)
C50.29165 (11)0.54034 (7)0.11057 (6)0.01275 (13)
H50.38670.49730.14120.015*
C60.19977 (11)0.48449 (7)0.03258 (6)0.01301 (13)
C70.05722 (11)0.54781 (7)−0.01256 (6)0.01242 (13)
C80.01464 (10)0.66497 (7)0.02168 (6)0.01194 (13)
H8−0.08120.7078−0.00840.014*
C8A0.10928 (10)0.72232 (7)0.09969 (6)0.01059 (12)
C100.14695 (12)1.03330 (8)0.22797 (7)0.01802 (15)
H10A0.10791.08540.17180.027*
H10B0.24831.07200.26110.027*
H10C0.05071.02420.27660.027*
C11−0.12539 (11)0.85179 (8)0.18297 (7)0.01757 (15)
H11A−0.15690.93650.20220.026*
H11B−0.12000.79980.24340.026*
H11C−0.21440.81890.13670.026*
C120.37900 (13)0.30406 (9)0.03586 (8)0.02182 (18)
H12A0.39100.22390.00200.033*
H12B0.35790.29080.10790.033*
H12C0.48740.35200.02690.033*
N10.19793 (9)0.91062 (6)0.18960 (5)0.01301 (12)
O10.23450 (9)0.37016 (6)−0.00665 (5)0.01876 (13)
O2−0.02759 (9)0.49009 (5)−0.08915 (5)0.01773 (13)
H2−0.10540.5372−0.11260.027*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0121 (3)0.0114 (3)0.0127 (3)0.0012 (2)−0.0006 (2)−0.0010 (2)
C30.0162 (3)0.0185 (3)0.0128 (3)−0.0004 (3)−0.0017 (3)−0.0026 (3)
C40.0142 (3)0.0154 (3)0.0148 (3)0.0000 (3)−0.0041 (3)−0.0009 (3)
C4A0.0107 (3)0.0121 (3)0.0119 (3)−0.0005 (2)−0.0007 (2)0.0007 (2)
C50.0119 (3)0.0119 (3)0.0144 (3)0.0011 (2)−0.0023 (2)0.0009 (2)
C60.0132 (3)0.0100 (3)0.0159 (3)0.0018 (2)−0.0021 (3)−0.0005 (2)
C70.0126 (3)0.0102 (3)0.0145 (3)0.0007 (2)−0.0027 (3)−0.0004 (2)
C80.0116 (3)0.0107 (3)0.0135 (3)0.0009 (2)−0.0023 (2)0.0000 (2)
C8A0.0103 (3)0.0100 (3)0.0115 (3)0.0001 (2)−0.0002 (2)0.0007 (2)
C100.0179 (4)0.0149 (3)0.0212 (3)0.0006 (3)0.0022 (3)−0.0053 (3)
C110.0121 (3)0.0191 (3)0.0215 (3)0.0012 (3)0.0012 (3)−0.0040 (3)
C120.0231 (4)0.0173 (3)0.0250 (4)0.0099 (3)−0.0070 (4)−0.0022 (3)
N10.0132 (3)0.0113 (3)0.0145 (3)−0.0006 (2)0.0010 (2)−0.0031 (2)
O10.0199 (3)0.0113 (2)0.0251 (3)0.0056 (2)−0.0085 (3)−0.0043 (2)
O20.0189 (3)0.0132 (2)0.0211 (3)0.0035 (2)−0.0097 (2)−0.0050 (2)

Geometric parameters (Å, °)

C1—N11.4780 (10)C7—O21.3555 (10)
C1—C8A1.5174 (10)C7—C81.3837 (10)
C1—C111.5386 (12)C8—C8A1.4045 (10)
C1—H11.0000C8—H80.9500
C3—N11.4703 (11)C10—N11.4722 (10)
C3—C41.5185 (12)C10—H10A0.9800
C3—H3A0.9900C10—H10B0.9800
C3—H3B0.9900C10—H10C0.9800
C4—C4A1.5110 (11)C11—H11A0.9800
C4—H4A0.9900C11—H11B0.9800
C4—H4B0.9900C11—H11C0.9800
C4A—C8A1.3892 (10)C12—O11.4257 (11)
C4A—C51.4070 (11)C12—H12A0.9800
C5—C61.3866 (11)C12—H12B0.9800
C5—H50.9500C12—H12C0.9800
C6—O11.3665 (10)O2—H20.8400
C6—C71.4139 (11)
N1—C1—C8A109.97 (6)C7—C8—C8A121.76 (7)
N1—C1—C11114.55 (6)C7—C8—H8119.1
C8A—C1—C11111.16 (7)C8A—C8—H8119.1
N1—C1—H1106.9C4A—C8A—C8119.42 (7)
C8A—C1—H1106.9C4A—C8A—C1122.58 (7)
C11—C1—H1106.9C8—C8A—C1117.99 (7)
N1—C3—C4109.96 (7)N1—C10—H10A109.5
N1—C3—H3A109.7N1—C10—H10B109.5
C4—C3—H3A109.7H10A—C10—H10B109.5
N1—C3—H3B109.7N1—C10—H10C109.5
C4—C3—H3B109.7H10A—C10—H10C109.5
H3A—C3—H3B108.2H10B—C10—H10C109.5
C4A—C4—C3110.99 (7)C1—C11—H11A109.5
C4A—C4—H4A109.4C1—C11—H11B109.5
C3—C4—H4A109.4H11A—C11—H11B109.5
C4A—C4—H4B109.4C1—C11—H11C109.5
C3—C4—H4B109.4H11A—C11—H11C109.5
H4A—C4—H4B108.0H11B—C11—H11C109.5
C8A—C4A—C5119.05 (7)O1—C12—H12A109.5
C8A—C4A—C4121.03 (7)O1—C12—H12B109.5
C5—C4A—C4119.90 (7)H12A—C12—H12B109.5
C6—C5—C4A121.49 (7)O1—C12—H12C109.5
C6—C5—H5119.3H12A—C12—H12C109.5
C4A—C5—H5119.3H12B—C12—H12C109.5
O1—C6—C5125.51 (7)C3—N1—C10111.00 (7)
O1—C6—C7115.09 (7)C3—N1—C1111.54 (6)
C5—C6—C7119.39 (7)C10—N1—C1112.10 (7)
O2—C7—C8123.81 (7)C6—O1—C12116.80 (7)
O2—C7—C6117.30 (7)C7—O2—H2109.5
C8—C7—C6118.87 (7)
N1—C3—C4—C4A−48.19 (9)C4—C4A—C8A—C1−0.30 (11)
C3—C4—C4A—C8A15.68 (11)C7—C8—C8A—C4A−1.26 (12)
C3—C4—C4A—C5−166.13 (7)C7—C8—C8A—C1178.70 (7)
C8A—C4A—C5—C6−0.56 (12)N1—C1—C8A—C4A16.96 (10)
C4—C4A—C5—C6−178.78 (7)C11—C1—C8A—C4A−110.97 (8)
C4A—C5—C6—O1179.31 (8)N1—C1—C8A—C8−163.01 (7)
C4A—C5—C6—C7−0.60 (12)C11—C1—C8A—C869.06 (9)
O1—C6—C7—O2−0.54 (11)C4—C3—N1—C10−165.48 (7)
C5—C6—C7—O2179.38 (7)C4—C3—N1—C168.74 (8)
O1—C6—C7—C8−179.10 (7)C8A—C1—N1—C3−50.54 (8)
C5—C6—C7—C80.82 (12)C11—C1—N1—C375.49 (8)
O2—C7—C8—C8A−178.36 (8)C8A—C1—N1—C10−175.71 (6)
C6—C7—C8—C8A0.10 (12)C11—C1—N1—C10−49.68 (9)
C5—C4A—C8A—C81.47 (11)C5—C6—O1—C12−0.82 (13)
C4—C4A—C8A—C8179.67 (7)C7—C6—O1—C12179.10 (8)
C5—C4A—C8A—C1−178.50 (7)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2···N1i0.841.902.6970 (10)159

Symmetry codes: (i) x−1/2, −y+3/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: ZL2131).

References

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