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

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 alpha-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 C-3-OH of compound 12 with C-28 carboxylic acid is a favorable modification to ameliorate the anticancer activity. Furthermore, alpha-L-rhamnosyl moiety linked to C-2-OH of the first monosaccharide (alpha-L-alabinose, beta-D-xylose, beta-n-galactose or beta-D-glucose) in C-3-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. (C) 2013 Elsevier Masson SAS. All rights reserved.