Artemisiverins A1-A32, structurally diverse guaiane-type sesquiterpenoid dimers from Artemisia sieversiana and their antihepatoma activity.

Abstract

Artemisiverins A1-A32 (1‒32), undescribed guaiane-type sesquiterpenoid dimers, and 23 known analogues (33‒55) were obtained from Artemisia sieversiana Ehrhart ex Willd. (Asteraceae). The structures of compounds 1‒32 were identified through comprehensive spectroscopic analysis, ECD calculations, and X-ray diffraction. These diverse scaffolds were biosynthetically derived from Diels-Alder reactions involving six different connection patterns and the formation of ester bonds, leading to construction of a previously reported linkage type of C-2‒C-3'/C-3‒C-1' for compound 8, the second example of an architecture featuring the linkage of C-2‒C-1'/C-3‒C-3' for compounds 1‒7, and the presence of unique hemiacetal moiety for compounds 15 and 16. The antihepatoma assay revealed that compound 6 significantly inhibited both HepG2 and Huh7 cells with ratios of 91.8% and 92.3% at 200 μM, respectively.