Artemisieverolides A—G, Sesquiterpenoid Trimers from Artemisia sieversiana and Their Antihepatic Fibrosis Activity

Comprehensive Summary Artemisieverolides A—G ( 1 — 7 ), seven unreported sesquiterpenoid trimers, were isolated from Artemisia sieversiana (Asteraceae), and elucidated by comprehensive spectral data and electronic circular dichroism (ECD) calculations. Compounds 1 , 2 , 4 and 6 were unambiguously determined by the single‐crystal X‐ray diffraction. Artemisieverolide A ( 1 ) was an unprecedented guaianolide sesquiterpenoid trimer featuring a rare 5/7/4/7/5 carbon skeleton biogenetically derived from [2+2] cycloaddition and a 2‐methylbicyclo[2.2.1]‐2‐heptene ring through a Diels‐Alder (D‐A) reaction. Artemisieverolides B—G ( 2 — 7 ) were guaianolide sesquiterpenoid trimers generated by two D‐A reactions. Compounds 3 , 4 , and 5 exhibited inhibitory activities on the proliferation of HSC‐LX‐2 with the IC 50 values of 52.6, 58.4, and 54.8 μmol/L, and were about 3 folds more active than silybin (IC 50 = 149.4 μmol/L). Furthermore, compounds 2 and 7 suppressed the expression of collagen I in TGF‐β1‐stimulated HSC‐LX‐2.