Crystal Structure and Absolute Configuration of Pendulone

Abstract

There are more than 20 species of Oxytropis distributed in different regions of China. Most of the Oxytropis species are highly poisonous to livestock. For sheep and cattle, lengthy exposure will result in chronic intoxication with such symptoms as emaciation, acyesis, abortus, still birth or abnormalities, and may even cause death. To establish biomedical applications of the poisonous species, a careful phytochemistry investigation of the roots of Oxytropis falcata Bunge collected in China in 2006, was carried out by our group.The air-dried roots of O. falcata (0.5 kg) were extracted three times (each for 7 days) successively with EtOH at room temperature. The resultant extract was concentrated under reduced pressure to yield a residue (90 g), which was suspended in water and fractionated by successive partitioning with petroleum ether (60 -90˚C), EtOAc and 1-BuOH. The EtOAc fraction (10 g) was subjected to repeated column chromatography. The title compound (20 mg), as one of the components, was isolated. The NMR and MS spectroscopy analysis of this compound disclosed its isoflavanquinonic skeleton and pattern of substitution, which was determined to be 7-hydroxy-3¢,4¢-dimethoxyisoflavanquinone, the first report of isoflavanquinone from this genus, previously identified as pendulone. 1 However, the absolute configuration remained unknown. The CD spectrum of pendulone, correlated with that of (3R)-Astragaluquinone, 2 exhibited a positive cotton effect in the 270 -300 nm region. Thus, pendulone was defined unambiguously by its 3R absolute stereochemistry.Leishmaniasis is endemic in tropical regions, currently prevalent throughout the world, and in at least 88 countries. 3 In a previous investigation, pendulone exhibited remarkable in vitro antileishmanical activity with an IC50 value of 0.07 mg/ml. 4The interesting biological activity of the title compound has stimulated efforts toward a detailed X-ray analysis to disclose its inherent three-dimensional structure, and has provided scientists with tools to understand the biological mechanisms of action and to develop animal models for human diseases.Red crystals suitable for an X-ray structural analysis were obtained by slowly evaporating from a petroleum ether-acetone solution at room temperature. The crystal and experiment data are given in Table 1. The structure was solved by direct methods and refined with anisotropic temperature factors for non-H atoms. All H atoms, except for that of the hydroxyl group, which was found from difference Fourier maps, were calculated geometrically. The atomic parameters of the non-hydrogen The complete structure of the title compound, C17H16O6, isolated from the roots of Oxytropis falcata Bunge, was confirmed unambiguously by a single-crystal X-ray analysis. The absolute configuration was established by circular dichroism (CD). The bond distances and angles are within the expected ranges. The quinone ring is linked to the chroman ring by C(3) at an equatorial position. The crystal structure is also stabilized by intermolecular ...

Oxytrofalcatins A–F, N-benzoylindole analogues from the roots of Oxytropis falcata (Leguminosae)

“…As part of an ongoing investigation on the secondary metabolites produced by toxic plants (Chen et al, 2008(Chen et al, , 2009, six new indole alkaloids, named oxytrofalcatins A-F (1-6), together with five known metabolites (7)(8)(9)(10)(11), were isolated from the roots of O. falcata. This paper deals with the isolation, structure elucidation, and biological evaluation of 1-6, together with a summary of the postulated biogenesis of the new analogues, as well as related natural products.…”

Antiparasitic and Antimicrobial Isoflavanquinones from Abrus schimperi

“…The specific rotation values of 1 and 2 ([] D 25 -22, c 0.5 and [] D 25 -5, c 0.5), taken in MeOH, were found to be significantly lower as compared to those reported for amorphaquinone ([] D -92.9, solvent: not reported) [15] and pendulone ([] D -42, c 2.0, MeOH) [16]), respectively. On the other hand, the Circular Dichroism (CD) spectra of pendulone with C-(3R) absolute configuration was not in agreement with those recorded for 2 [11,17]. Therefore, this discrepancy and availability of compounds 1 and 2 offered the opportunity to assess and report the complete CD data to define their absolute stereochemistry (Figure 2).…”

“…On the other hand, the Circular Dichroism (CD) spectra of pendulone with C-(3 R ) absolute configuration was not in agreement with those recorded for 2 [11, 17]. Therefore, this discrepancy and availability of compounds 1 and 2 offered the opportunity to assess and report the complete CD data to define their absolute stereochemistry (Figure 2).…”

“…Both the compounds exhibited two high amplitude positive Cotton Effects (CEs) in the 300-360 nm and 400-450 nm regions, and a high amplitude negative CE in 450-550 nm regions. However, (3 R ) absolute configuration of pendulone [17] was based on a correlation of a single positive CE in 270-300 nm region with those for (3 R )-astragaluquinon [18]. At the same time, C-(3 R ) absolute configuration of astragaluquinon [18] was assigned based on correlation between its CD spectrum and ORD spectra of (3 S )- and (3 R )-mucroquinone [13, 19].…”

“…It means that, assignments of absolute stereoconfiguration based simply on similarity of CD and ORD spectra are not valid. Only complex analysis of the ORD curve shape can provide the information sufficient for correlation with CD curve, which was not followed in the published reports [11, 17, 18]. …”