(−)-Istanbulin A

Matías López-Rodríguez; Matías Reina; D M Domínguez-Díaz; V Fajardo; L Villarroel

doi:10.1107/S1600536809033418

. 2009 Sep 5;65(Pt 10):o2330. doi: 10.1107/S1600536809033418

(−)-Istanbulin A

Matías López-Rodríguez ^a, Matías Reina ^b, D M Domínguez-Díaz ^b, V Fajardo ^c, L Villarroel ^d,^*

PMCID: PMC2970221 PMID: 21577801

Abstract

The title compound (systematic name: 9a-hydroxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexahydro-4H,5H-naphtho[2,3-b]furan-2,8-dione), C₁₅H₂₀O₄, is a sesquiterpene lactone showing the typical eremophilanolide skeleton, which has been isolated from the plant Senecio candidans collected in the Chilean Magallanes region. The present study confirms the atomic connectivity assigned on the basis of ¹H and ¹³C NMR spectroscopy, as well as the relative stereochemistry of the 4α-methyl,5α-methyl,8β-hydroxy,10β-H unit. The crystal structure is stabilized by intermolecular O—H⋯O hydrogen bonds involving the hydroxy group as donor and the oxo group as acceptor, giving chains along the a axis. The absolute structure was not determined because of the lack of suitable anomalous scatters.

Related literature

For the biological activity of metabolites isolated from plants of the Senecio species, see: Ulubelen et al. (1971 ▶); Burgueño-Tapia et al. (2007 ▶); Domínguez et al. (2008 ▶); Reina,González-Coloma, Domínguez-Díaz et al. (2006 ▶); Reina, González-Coloma, Gutiérrez et al. (2006 ▶).

Experimental

Crystal data

C₁₅H₂₀O₄
M _r = 264.31
Monoclinic,
a = 7.432 (4) Å
b = 13.010 (6) Å
c = 8.161 (6) Å
β = 115.47 (4)°
V = 712.4 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.45 × 0.35 × 0.25 mm

Data collection

Enraf–Nonius KappaCCD diffractometer
Absorption correction: none
4410 measured reflections
1678 independent reflections
1485 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.095
S = 1.04
1678 reflections
186 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: SCALEPACK and DENZO (Otwinowski & Minor, 1997 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶ ); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: Win GX (Farrugia,1999 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809033418/hg2542sup1.cif

e-65-o2330-sup1.cif^{(19.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809033418/hg2542Isup2.hkl

e-65-o2330-Isup2.hkl^{(81KB, 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⋯O4ⁱ	0.90 (4)	1.87 (4)	2.750 (3)	164 (4)

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The Senecio (Asteraceae) genus are widely distributed by the worldwide and the most studied constituents are sesquiterpenes with eremophilanolides and furanoeremophilanes skeleton, together with pyrrolizidine alkaloids. The chemical study of plants of the Senecio species has increased in the last few years because of the biological activity that shown the metabolites isolated from this natural sources: Reina, González-Coloma, Domínguez-Díaz et al. (2006); Reina, González-Coloma, Gutiérrez et al. (2006); Burgueño-Tapia et al. (2007); Domínguez et al. (2008).

As part of our ongoing study of Senecio genus from the chilean shouthern and Magallanes Region, in this work we report the isolation and the molecular and crystal structure determination of the title compound, which it is described for the first time as a metabolite for the Senecio genus. An Istanbulin A with optical rotation [α]_D²⁵ = + 81.5° was reported some years ago and its structure and stereochemistry determined by spectroscopic methods, but no X-ray analysys was performed (Ulubelen et al.,1971). The lack of suitable anomalous scatters did not allow us to reliably determine the absolute structure and that shown: 1-oxo-8β-hydroxy-10βH-eremophil-7(11)-en-12,8β-olide was chosen to be, on the basis of the negative optical rotation value: [α]_D²⁵ = - 68.7°, the opposite to that the previously reported compound.

The crystal structure is stabilized by intermolecular O—H···O hydrogen bonds in which are involved the hydroxyl group at C8 acting as donor and the oxo group at C1 as acceptor, giving chains along the a axis, through a C(7) graph-set motif.

Experimental

Senecio candidans DC. (Asteraceae) was collected from the south of Chile, at the Santa Maria River, Punta Arenas(XII Region), in april 2002 and authenticated by Professor E. Pisano. A voucher specimen (n° 3483) was deposited in the herbarium of Instituto de la Patagonia, Universidad de Magallanes, Punta Arenas (Chile).

Dried aerial parts of S.candidans (3.5 kg) was extracted in methanol at room temperature during a week to give a crude methanolic extract (224 g), 6.4% yield of dry plant weight. A portion of these crude methanolic extract (124 g) was chromatographed on a silica gel vacuum-liquid chromatography column (VLC), using a hexane-ethyl acetate-methanol gradient. The portion of the extract collected at the (hexane-ethyl acetate, 75:25) solvent polarity (2.7 g) was further purified by passage over Sephadex LH-20 (hexane-methylene chloride-methanol, 3:1:1), followed by different chromatographic techniques to give (-)-Istanbuline A: 1-oxo-8β-hydroxy-10βH-eremophil-7(11)-en-12,8β-olide (6.4 mg). The molecular formula C₁₅H₂₀O₄ was deduced from its high resolution MS spectrum which shows a molecular ion at m/z=264.1357. Complete and unambiguous assignment of de all protons and carbon were established by analysis of the mono and bidimensional NMR experiments and comparison with the previously spectroscopic data reported for Istanbulin A (Ulubelen et al.,1971).

The absolute structure was not determined because of the lack of suitable anomalous scatters. However, the value of the measured optical rotation: [α]_D²⁵ = -68.7° allowed to us to choose that shown, as the opposite to that a previously described (+)-istanbulin: [α]_D²⁵ = +81.5°.