Synthesis and antitumor activities of naturally occurring oleanolic acid triterpenoid saponins and their derivatives

Abstract

Twenty-six naturally occurring oleanolic acid saponins and their derivatives, 16 of which were synthesized in this study, were preliminarily evaluated against human cancer cells. From SAR studies, the presence of α-l-rhamnosyl residue at the terminal of both C-3 and C-28 position for oleanolic acid bidesmosides was important to enhance cytotoxicity, and introducing more sugar residues at C3-OH of compound 12 with C-28 carboxylic acid is a favorable modification to ameliorate the anticancer activity. Furthermore, α-l-rhamnosyl moiety linked to C2-OH of the first monosaccharide (α-l-alabinose, β-d-xylose, β-d-galactose or β-d-glucose) in C3-OH of oleanolic acid was helpful to improve the cytotoxicity. According to the predicted log P values, lipophilicity of the synthesized saponins was not an important factor for cytotoxicity.