Six Pairs of Enantiomeric Phthalide Dimers from the Rhizomes of Ligusticum Chuanxiong and Their Absolute Configurations and Anti-Inflammatory Activities

Abstract

Six pairs of enantiomeric phthalide dimers (1–6) were isolated from the rhizomes of Ligusticum chuanxiong. Their structures and absolute configurations were elucidated by NMR spectroscopy, X-ray diffraction analyses, and electronic circular dichroism calculations. Compounds (+)-1 and (−)-1 are new phthalide dimers, featuring two classes of monomeric units (a phthalide and an unusual 2,3-seco-phthalide) with an uncommon linkage (3,6ʹ/8,3ʹa). Compounds (+)-2 and (−)-3 are also novel phthalide dimers that had not been reported previously. Although (−)-2 and (+)-3 have been successfully isolated in previous studies, their absolute configurations were not unambiguously determined. As for compound 4, it was reported as a racemate in one study, and one of its enantiomers was identified in a subsequent study. Herein, all enantiomeric phthalide dimers were successfully separated, and their absolute configurations were determined. The inhibitory effects of all isolates against lipopolysaccharide-induced nitric oxide production were tested using RAW264.7 cells. The results show that compounds (+)-2, (−)-2, (+)-3, (−)-3, (+)-4, (−)-4, (+)-5, (+)-6, and (−)-6 have significant inhibitory activities, with compound (+)-5 being the most active (IC50 value of 4.32 ± 1.33 μM).

Keywords: Ligusticum chuanxiong, phthalide dimers, enantiomers, absolute configurations, anti-inflammatory activity