8β-Acet­oxy-14α-benzo­yloxy-N-ethyl-3α,10β,13β,15α-tetra­hydr­oxy-1α,6α,16β-trimeth­oxy-4β-(methoxy­methyl­ene)aconitane: aconifine from Aconitum karakolicum Rapaics

Bakhodir Tashkhodjaev; Mukhlis N Sultankhodjaev

doi:10.1107/S1600536809021436

. 2009 Jun 10;65(Pt 7):o1543–o1544. doi: 10.1107/S1600536809021436

8β-Acetoxy-14α-benzoyloxy-N-ethyl-3α,10β,13β,15α-tetrahydroxy-1α,6α,16β-trimethoxy-4β-(methoxymethylene)aconitane: aconifine from Aconitum karakolicum Rapaics

Bakhodir Tashkhodjaev ^a,^*, Mukhlis N Sultankhodjaev ^a

PMCID: PMC2969206 PMID: 21582830

Abstract

The title compound, C₃₄H₄₇NO₁₂, is the norditerpenoid alkaloid aconifine isolated from the leaves and tubers of Aconitum karakolicum Rapaics. It has a lycoctonine carbon skeleton and contains four six-membered rings and two five-membered rings; its geometry is similar to that observed in other lycoctonine-type diterpenoid alkaloids. There are two intramolecular O—H⋯O hydrogen bonds which close five- and seven-membered pseudo-rings, respectively. In the crystal, two intermolecular O—H⋯O hydrogen bonds cross-link the molecules into double chains along the a axis.

Related literature

For the isolation of aconifine, see: Sultankhodzhaev et al. (1973 ▶). For spectroscopic data and the chemical structure of aconifine, see: Sultankhodzhaev et al. (1980 ▶). For the neurocardiotoxic activity of aconifine, see: Dzhakhangirov et al. (1997 ▶). For the neurocardiotoxic activity of lycoctonine alkaloids, see: Dzhakhangirov et al. (1976 ▶). For general background to lycoctonine alkaloids and their structures, see: Joshi & Pelletier (1987 ▶).

Experimental

Crystal data

C₃₄H₄₇NO₁₂
M _r = 661.73
Orthorhombic,
a = 12.0213 (3) Å
b = 15.4938 (6) Å
c = 17.1038 (4) Å
V = 3185.68 (16) Å³
Z = 4
Cu Kα radiation
μ = 0.87 mm⁻¹
T = 100 K
0.40 × 0.30 × 0.25 mm

Data collection

Oxford Diffraction Xcalibur Ruby diffractometer
Absorption correction: multi-scan (CrysAlisPro; Oxford Diffraction, 2009 ▶) T _min = 0.767, T _max = 0.811
11111 measured reflections
6334 independent reflections
6050 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.098
S = 1.06
6334 reflections
451 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ▶), 2633 Friedel pairs
Flack parameter: 0.04 (10)

Data collection: CrysAlisPro (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlisPro; data reduction: CrysAlisPro; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809021436/zl2215sup1.cif

e-65-o1543-sup1.cif^{(27.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809021436/zl2215Isup2.hkl

e-65-o1543-Isup2.hkl^{(310KB, 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
O11—H11⋯O5	0.83 (3)	2.07 (3)	2.791 (2)	146 (3)
O8—H8⋯O12	0.83 (3)	2.11 (3)	2.598 (2)	117 (3)
O2—H2⋯O7ⁱ	0.87 (3)	2.21 (3)	3.066 (2)	168 (3)
O8—H8⋯O2ⁱⁱ	0.83 (3)	2.39 (3)	2.928 (2)	123 (3)

Open in a new tab

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

Acknowledgments

We thank the Academy of Sciences of Uzbekistan for supporting this study.

supplementary crystallographic information

Comment

The norditerpenoid alkaloid aconifine was isolated from leaves and tubers of Aconitum karakolicum Rapaics (Sultankhodzhaev et al.,1980). It exhibits neurocardiotoxic properties (Dzhakhangirov et al., 1997) similar to those of aconitine (Dzhakhangirov et al., 1976). The molecular structure of the title compound is shown in Fig. 1. Aconifine has a lycoctonine carbon skeleton; its geometry is similar to that observed in other lycoctonine type diterpenoid alkaloids (Joshi et al.,1987).

The lycoctonine carbon skeleton, contains four six-membered rings, (A, C, E and F), and two five-membered rings (B and D) (Fig. 2). Rings A and C have more or less regular chair conformations, whereas ring F shows significant distortions and ring E adopts a sofa conformation. The five-membered rings B and D have envelope conformations.

The position and orientation of the 10 oxo substituents on the carbon lycoctonine skeleton are 1α, 3α, 4β, 6α, 8β, 10β, 13β, 14α, 15α, 16β, which confirms the earlier structure assignment based on spectral data (Sultankhodzhaev et al., 1980).

In the crystal structure of the title compound there are four acidic H atoms that can participate in H-bonds. The H8 and H11 hydroxyl hydrogen atoms take part in intramolecular H-bonds which close 5 and 7-membered pseudo-cycles, respectively. Hydroxyl hydrogen atom H7 does not take a part in any H-bonding interactions. Atoms H2 and H8 participate in intermolecular O—H···O bonds which link the molecules into infinite double chains along the a-axis (Table 1; Fig.3). The hydrogen atom H8 forms a bifurcated H-bond to both O2 and O7.

Experimental

The title compound was isolated from the chloroform fraction of the tubers of Aconitum karakolicum Rapaics by a known method (Sultankhodzhaev et al., 1973). Crystals suitable for X-ray analysis were obtained by slow evaporation of a methanol solution at room temperature (m.p. 471–473 K).