(1α,8β)-6β-Benzo­yloxy-6-dehydroxy­heteratisine from Aconitum zeravschanicum

Bakhodir Tashkhodjaev; Bakhodir T Salimov

doi:10.1107/S1600536809023873

. 2009 Jun 27;65(Pt 7):o1682–o1683. doi: 10.1107/S1600536809023873

(1α,8β)-6β-Benzoyloxy-6-dehydroxyheteratisine from Aconitum zeravschanicum

Bakhodir Tashkhodjaev ^a,^*, Bakhodir T Salimov ^a

PMCID: PMC2969503 PMID: 21582940

Abstract

The title compound, C₂₉H₃₇NO₆, was isolated from Aconitum zeravschanicum and exhibits antiarhythmic activity. It is a derivative of the diterpenoid alkaloid heteratisine and as such the core framework of the molecule contains four six-membered, three seven-membered and one five-membered ring. The chair conformation of one of the methoxy-substituted six-membered rings is different from that observed in heteratisine hydrobromide monohydrate. In the latter case, this ring adopts a boat conformation due to a stabilizing intramolecular N—H⋯O hydrogen bond. In the crystal structure of the title compound, there is only one acidic H atom. This hydroxyl group forms an intermolecular O—H⋯O hydrogen bond that links molecules into infinite chains along the b axis.

Related literature

For the isolation and idenfication of 6-benzoylheteratisine, see: Aneja et al. (1973 ▶), Jacobs et al. (1947 ▶), Nigmatullaev et al. (2000 ▶). For antiarhythmic activity, see: Salimov et al. (1996 ▶). For the structure of heteratisine hydrobromide monohydrate, see: Przybylska (1965 ▶).

Experimental

Crystal data

C₂₉H₃₇NO₆
M _r = 495.60
Orthorhombic,
a = 10.039 (5) Å
b = 14.107 (8) Å
c = 17.512 (6) Å
V = 2480 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 300 K
0.50 × 0.30 × 0.15 mm

Data collection

Stoe Stadi-4 four-circle diffractometer
Absorption correction: none
2481 measured reflections
2481 independent reflections
1667 reflections with I > 2σ(I)
3 standard reflections every 200 reflections intensity decay: 6.8%

Refinement

R[F ² > 2σ(F ²)] = 0.067
wR(F ²) = 0.142
S = 1.22
2481 reflections
330 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: STADI4 (Stoe & Cie, 1997 ▶); cell refinement: STADI4; data reduction: X-RED (Stoe & Cie, 1997 ▶); 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/S1600536809023873/zl2222sup1.cif

e-65-o1682-sup1.cif^{(23.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809023873/zl2222Isup2.hkl

e-65-o1682-Isup2.hkl^{(121.9KB, 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—H3⋯O1ⁱ	0.82	2.25	3.056 (8)	166

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

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

supplementary crystallographic information

Comment

The title compound of this study, 6-benzoylheteratisine, C₂₉H₃₇NO₆, was first obtained synthetically in 1973 (Aneja et al., 1973) and found to be a derivative of a naturally occuring compound (Jacobs et al. 1947). Later it was isolated from Aconitum zeravschanicum Steinb (Nigmatullaev et al. 2000). 6-Benzoylheteratisine exibits antiarhythmic activity that exceeds other antiarrhythmic drugs of the quinidine groups (Salimov et al. 1996). The crystal structure of the parent compound was previously established as a salt in the form of heteratisine hydrobromide monohydrate (Przbylslka, 1965).

The molecular structure of the title compound is shown in Fig. 1. The heteratisine skeleton contains four six-membered rings, (A, C, D and F), one five-membered ring (B), and three seven-membered rings (e.g. E, others not labeled for clarity) (Fig. 2). Ring B has an envelope and ring Ca more or less regular chair conformation. Ring F shows a significant distortion and rings D and E adopt a boat conformations. The chair conformation of ring A in the title molecule is different from that observed in heteratisine hydrobromide monohydrate (Przybylska, 1965). For the salt of the parent compound ring A adopts a boat conformation due to a stabilizing intramolecular N—H···O hydrogen bond between the protonated amine towards the oxygen atom, an interaction not present in the title compound.

The aromatic ring and the acyl-group are rotated against each other, the dihedral angle of their respective planes is 32.6 (9)°. There is only one acidic hydrogen atom in the crystal structure of the title compound. This hydroxyl group forms an intermolecular O—H···O hydrogen bond that links the molecules into infinite chains along the b-axis. (Table 1; Fig.3)

Experimental

The title compound was isolated from the chloroform fraction of the leaves of Aconitum zeravschanicum by a known method (Nigmatullaev et al., 2000). Crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution at room temperature (m.p. 485–487 K).