Graveoumarins A–C: chiral resolution, absolute configuration, and anticoagulant/anti-inflammatory activities of 3′-methyl-3′-butenyl coumarins from ruta graveolens L

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Context Several coumarins have been isolated from Ruta graveolens L., but the chirality of many remains uncharacterized or their absolute configurations unresolved.Objective This study aimed to comprehensively separate and characterize the chirality of 3′-methyl-3′-butenylcoumarins from R. graveolens extracts, determine their absolute configurations, and evaluate their anticoagulant and anti-inflammatory activities.Materials and methods Comprehensive chromatographic separation and chiral HPLC analysis were employed on the R. graveolens extract. The structures of isolated compounds were elucidated using extensive spectroscopic data analysis (HR-ESI-MS, NMR) and by comparing experimental circular dichroism (CD) spectra with calculated electronic circular dichroism (ECD) spectra. The anticoagulant and anti-inflammatory (specifically inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages) activities of the isolated compounds were evaluated.Results The study led to the isolation of two pairs of enantiomeric 3′-methyl-3′-butenylcoumarins, present in both equivalent and inequivalent ratios. This included two previously undescribed chiral 3′-methyl-3′-butenylcoumarins with specific absolute configurations [(+)-2′R-2 and (–)-2′S-3] and one undescribed achiral 3′-methyl-3′-butenylcoumarin (1). Among the tested compounds, only the racemic mixture (±)-3 exhibited moderate inhibition of NO production in the anti-inflammatory assay. No significant anticoagulant activity was reported for the compounds.Conclusions This study successfully characterized the chirality and determined the absolute configurations of specific 3′-methyl-3′-butenylcoumarins from R. graveolens, including the discovery of three new compounds. While most isolated compounds lacked significant anticoagulant or anti-inflammatory activity in the tested models, racemic (±)-3 showed moderate anti-inflammatory potential by inhibiting NO production. These findings provide new insights for the future development and utilization of coumarins from R. graveolens.

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