Mesaconitine

Dao-Hang He; Yong-Chuang Zhu; Ai-Xi Hu

doi:10.1107/S1600536808013147

. 2008 May 10;64(Pt 6):o1033–o1034. doi: 10.1107/S1600536808013147

Mesaconitine

Dao-Hang He ^a,^*, Yong-Chuang Zhu ^a, Ai-Xi Hu ^b

PMCID: PMC2961389 PMID: 21202557

Abstract

The title compound, (1α,3α,6α,14α,15α,16β)-3,8,13,14,15-pentahydroxy-1,6,16-trimethoxy-4-methoxymethyl-20-methylaconitan-8,14-diyl 8-acetate 14-benzoate, C₃₃H₄₅NO₁₁, a C₁₉ diterpenoid alkaloid, obtained from the roots of Aconitum kusnezoffii, has been crystallographically characterized in this study. Rings A, B and E have chair conformations, rings C and F display envelope conformations, and ring D adopts a boat conformation. There are inter- and intramolecular O—H⋯O hydrogen bonds, the latter resulting in the formation of a non-planar seven-membered ring. The intermolecular interactions link the molecules into a two-dimensional network.

Related literature

For general background, see: Hikino et al. (1980 ▶); Li et al. (1997 ▶); Mitamura et al. (2002 ▶); Saito et al. (1982 ▶); For ring conformation details, see: Codding (1982 ▶); De Camp & Pelletier (1977 ▶); Parvez et al. (1999 ▶); Pelletier et al. (1982 ▶). For related literature, see: Pelletier & Djarmati (1976 ▶); Tsuda & Marion (1963 ▶); Zhapova et al. (1986 ▶).

Experimental

Crystal data

C₃₃H₄₅NO₁₁
M _r = 631.70
Orthorhombic,
a = 12.6820 (6) Å
b = 15.3848 (7) Å
c = 15.6110 (7) Å
V = 3045.9 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 173 (2) K
0.46 × 0.35 × 0.12 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.954, T _max = 0.988
18319 measured reflections
3713 independent reflections
3026 reflections with I > 2σ(I)
R _int = 0.042

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.081
S = 1.07
3713 reflections
418 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT-Plus (Bruker, 2003 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808013147/wn2256sup1.cif

e-64-o1033-sup1.cif^{(31.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808013147/wn2256Isup2.hkl

e-64-o1033-Isup2.hkl^{(182.1KB, 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
O10—H10A⋯O2	0.84	2.11	2.788 (3)	138
O7—H7⋯O8	0.84	2.04	2.560 (3)	120
O4—H4⋯O11ⁱ	0.84	2.20	3.018 (3)	163

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Guangdong Provincial Natural Science Foundation of China (No. 04300531) for financial assistance.

supplementary crystallographic information

Comment

As an important Chinese herbal medicine belonging to the genus Aconitum, A. kusnzoffii has been therapeutically used to treat rheumatic pain, paralysis due to stroke, rheumatoid arthritis and some other inflammations. Mesaconitine, a C₁₉ diterpenoid alkaloid, is pharmacologically one of the most active components obtained from the roots of A. kusnezoffii (Li et al., 1997). Mesaconitine has been reported to have an anti-inflammatory activity (Hikino et al.,1980; Saito et al., 1982), and the vasorelaxant effect of mesaconitine may contribute to the therapeutical effectiveness on persons with a weak constitution and poor metabolism, by improving peripheral blood circulation (Mitamura et al., 2002). The three-dimensional structure of most biologically active molecules plays a role in governing their interactions and activities. It is important to obtain information on the mode of action and selectivity of mesaconitine so that it can be used safely and efficiently. Many X-ray crystal structure determinations of C₁₉ diterpenoid alkaloids have been reported, such as pseudaconitine, delphinine (Parvez et al., 1999; Pelletier et al., 1982.). However, the crystal structure of mesaconitine has not been reported. In view of this, the crystal structure determination of the title compound was carried out and the results are presented here.

The structure of mesaconitine is similar to that of aconitine (Codding, 1982). The only difference between aconitine and mesaconitine is a methylene group at the tertiary nitrogen atom. The bond lengths and angles in the title compound are in good agreement with expected values. In the molecule of the title compound, (Fig. 1), rings A, B and E have a chair conformation, rings C and F display an envelope conformation, ring D adopts a boat conformation. The packing of the title compound is shown in Fig. 2. In the crystal structure, there are inter- and intramolecular O—H···O hydrogen bonds. The former link the molecules into a two-dimensional network, while the latter results in the formation of a non-planar seven-membered ring. These intramolecular hydrogen bonds may be effective in the stabilization of the structure.

Experimental

The title compound was isolated from the roots of A. kusnezoffii according to the literature procedure of Li et al. (1997) and crystals of X-ray quality were grown from methanol at room temperature by slow evaporation.