Identification and biomimetic synthesis of iphionanes and cyperanes from Artemisia hedinii and their anti-hepatic fibrosis activity

Two new skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11) were isolated from the whole plant of Artemisia hedinii. The two new skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were established based on extensive analysis of spectroscopic data, including HR-ESIMS, 1D and 2D NMR spectra. The absolute configurations were determined by ECD spectra and single-crystal X-ray crystallographic analyses, time dependent density functional theory (TDDFT) electron circular dichroism (ECD) calculation, DFT NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two new skeletons (1 and 6) were inspired by potentially biogenetic pathways, using a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. In addition, all compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8 and 10 showed significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.