14-Benzoyl­mesaconine hydro­chloride methanol monosolvate

Yan Mu; Lin Li; Hai-Liu Wei; Tong-Chun Kuang; Song-Qing Hu

doi:10.1107/S1600536811010300

. 2011 Mar 26;67(Pt 4):o974–o975. doi: 10.1107/S1600536811010300

14-Benzoylmesaconine hydrochloride methanol monosolvate

Yan Mu ^a, Lin Li ^a, Hai-Liu Wei ^a, Tong-Chun Kuang ^b, Song-Qing Hu ^a,^*

PMCID: PMC3099831 PMID: 21754235

Abstract

The title compound, C₃₁H₄₄N₃O₁₀ ⁺·Cl⁻·CH₄O, is the methanol solvate of 8-benzoyloxy-,9,11,11a-tetrahydroxy-6,10,13-trimethoxy-3-methoxymethyl-1-methyltetradecahydro-1H-3,6a,12-(epiethane-1,1,2-triyl)-7,9-methanonaphtho[2,3-b]azocin-1-ium chloride, the amine-protonated hydrochloride of 14-benzoylmesaconine hydrochloride. The cation has an aconitine carbon skeleton with four six-membered rings of which three display chair conformations and one a boat conformation, and two five-membered rings with envelope conformations. In the crystal, the components are connected into an infinite chain by inter- and intramolecular O—H⋯O, N—H⋯O and O—H⋯Cl hydrogen bonds.

Related literature

For general background to diterpenoid alkaloids, see: Ameri (1998 ▶); Desai et al. (1998 ▶); Suzuki et al. (1994 ▶). For the chemical structure of the title compound established from MS data, see: Zhang et al. (2005 ▶); Wang et al. (2009 ▶); Yue et al. (2009 ▶). For background to the strong toxicity of Aconitum alkaloids, see: Zhang et al. (2002 ▶). For ring numbering and ring conformations of the title compound, see: He et al. (2008 ▶).

Experimental

Crystal data

C₃₁H₄₄NO₁₀ ⁺·Cl⁻·CH₄O
M _r = 658.16
Orthorhombic,
a = 12.919 (3) Å
b = 15.748 (3) Å
c = 16.045 (3) Å
V = 3264.2 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 123 K
0.30 × 0.20 × 0.20 mm

Data collection

Rigaku/MSC Mercury CCD diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998 ▶) T _min = 0.969, T _max = 0.977
29100 measured reflections
6908 independent reflections
4585 reflections with I > 2σ(I)
R _int = 0.050

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.151
S = 1.10
6908 reflections
422 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.50 e Å⁻³
Absolute structure: Flack (1983 ▶), 1726 Friedel pairs
Flack parameter: −0.01 (11)

Data collection: RAPID-AUTO (Rigaku, 1998 ▶); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811010300/zl2352sup1.cif

e-67-0o974-sup1.cif^{(27.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811010300/zl2352Isup2.hkl

e-67-0o974-Isup2.hkl^{(338.1KB, 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
O3—H3A⋯O5	0.82	2.11	2.612 (4)	119
O3—H3A⋯O11	0.82	2.22	2.923 (4)	144
O4—H4A⋯Cl1	0.82	2.30	3.083 (3)	161
O6—H6⋯Cl1	0.82	2.40	3.197 (3)	165
O9—H9⋯O11ⁱ	0.82	1.98	2.776 (4)	163
N1—H1⋯O8	0.90 (2)	2.11 (4)	2.808 (4)	134 (4)
N1—H1⋯O9	0.90 (2)	2.20 (4)	2.795 (5)	123 (4)
O11—H11⋯Cl1ⁱⁱ	0.82	2.30	3.084 (3)	158

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

Acknowledgments

This project was supported by the Fundamental Research Funds for the Central Universities, SCUT (grant No. 20092Z0011). We thank Dr Yan-Wei Ren and Professor Lei Zhang for technical support.

supplementary crystallographic information

Comment

Aconitum species such as e.g. Aconitum Caremichaeli Debx. have been widely used in Chinese Traditional Medicine, and its tubers and roots have found therapeutical use for the treatment of for example rheumatic pain, rheumatoid arthritis and some other inflammations. Aconitine-type alkaloid extracts from the roots of Aconitum Caremichaeli Debx. are reported to have, among others, analgetic, diuretics, anti-inflammatory and cardiotonic properties (Ameri, 1998; Desai et al., 1998; Suzuki et al., 1994). At the same time, owing to their strong toxicity, poisoning with these Aconitum alkaloids does frequently happen (Zhang et al., 2002). Therefore, in order to better understand the pharmacology of the Aconitum alkaloids it is desirable to establish their molecular structures. The diterpenoid alkaloid 14-benzoylmesaconine, the title compound, was previously isolated from Aconitum Caremichaeli Debx., and its structure was established from the MS data (Zhang et al., 2005; Wang et al., 2009; Yue et al., 2009). However, there are no reports on the crystal structure or the NMR data of 14-benzoylmesaconine. In this paper, we would like to present the crystal structure and NMR data of the title compound, the hydrochloride salt of 14-benzoylmesaconine as its mono methanol solvate.

The molecular structure of the title compound is shown in Fig. 1. There is one cation, protonated at the amine N atom, one chloride anion and one methanol solvate molecule in the asymmetric unit of the structure. The bond lengths and angles are in good agreement with expected values. For ring naming (Figure 2) and ring conformations please refer to He et al. (2008). The cation of the title compound has an aconitine carbon skeleton with four six-membered rings and two five-membered rings. Six-membered rings A (C16/C21/C23/C24/C25/C26) and B (C9/C10/C15/C16/C17/C18) adopt chair conformations, six-membered heterocyclic ring E (N1/C17/C21/C22/C23) adopts a chair conformation, and the six-membered ring D (C8/C9/C12/C13/C14/C15) adopts a boat conformation. The two five-membered rings C (C16/C17/C18/C19/C21) and F (C8/C9/C10/C11/C12) adopt envelope conformations (Fig. 2). Intermolecular O—H···O hydrogen bonds between the hydroxyls of the cations and the hydroxy O atoms of the methanol solvate molecules lead to infinite chains. The chains are further connected with each other via intermolecular O—H···Cl hydrogen bonding interactions involving the hydroxyls of methanol molecules and the cations as donors and the chloride anions as acceptors to form 1D double-chains along to the a axis (Table 1, Fig. 3). Within the hydrogen-bonded double-chain the chloride anions are bonded to three hydroxyl groups, two from one cation and another one from a methanol solvate molecule. Each cation donates four hydrogen bonds to two methanol solvate molecules and one chloride anion, whilst each methanol solvate molecule donates one hydrogen bond to chloride anion and acceptes two hydrogen bonds from two hydroxyl groups of two cations. In addition, intramolecular N—H···O and O—H···O hydrogen bonds are also observed within the double-chain. Finally, the chains are linked into a three-dimensional supramolecular network through intermolecular O—H···O and O—H···Cl hydrogen-bonding interactions.

Experimental

Air-dried and powdered roots of Aconitum Caremichaeli Debx. (20 kg) were extracted with 90% EtOH (40 L) under reflux with a Soxhlet extractor. After the removal of solvent, the extract residue (200 g) was successively eluted in a macroporous resin by elution with water (5 L), 30% EtOH (5 L), 60% EtOH (5 L) and 90% EtOH (5 L), and different extract fractions were obtained. From the 30% EtOH fraction, a black amorphous powder (50 g) was obtained after the removal of the solvent under reduced pressure, which then was chromatographed on a silica gel (200–300 mesh) column, eluted with a chloroform-MeOH (99:1 to 1:1) gradient system, to give 25 fractions (2 L per fraction). The title compound (2 g) can be isolated between the eighteenth and twentieth fractions (yield 0.01%). Single crystals suitable for X-ray diffraction were prepared by slow evaporation of a solution of the title compound in CHCl₃ at room temperature. [¹H NMR(CDCl₃, δ, p.p.m.) 8.08 (d, 2H), 7.58 (t, 1H), 7.45 (t, 2H), 5.01 (d, 1H), 4.58 (d, 1H), 4.17 (t, 2H), 3.70 (s, 3H), 3.57 (d, 2H), 3.39 (t, 2H), 3.30–3.34 (m, 15H), 3.21 (d, 1H), 2.94 (s, 3H), 2.56 (s, 2H), 2.40 (d, 2H), 2.23 (t, 2H), 1.81 (d, 1H), 1.56 (d, 1H); ¹³C NMR (CDCl₃, δ, p.p.m.) 167.88, 134.45, 131.68, 131.20, 129.66, 93.60, 83.20, 81.48, 83.20, 81.48, 80.90, 79.15, 78.38, 76.36, 70.79, 68.38, 62.44, 59.67, 58.76, 55.76, 53.13, 52.06, 50.07, 45.55, 44.86, 43.76, 42.20, 41.91, 37.41, 30.62].