Synthesis and Cytotoxicity of Bidesmosidic Betulin and Betulinic Acid Saponins

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2009-01, Vol.72 (1), p.72-81
• Main Authors: Gauthier, Charles, Legault, Jean, Lavoie, Serge, Rondeau, Simon, Tremblay, Samuel, Pichette, André
• Format: Article
• Language: English
• Subjects: anticarcinogenic activity; Antineoplastic agents; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; arabinose; Betula papyrifera; betulin; betulinic acid; bidesmoside; Biological and medical sciences; chemical structure; cultured cells; cytotoxicity; Drug Screening Assays, Antitumor; General aspects; glycosides; glycosidic linkages; Humans; lupane triterpenes; Medical sciences; medicinal properties; Molecular Structure; Pharmacology. Drug treatments; phytochemicals; rhamnose; Saponins - chemical synthesis; Saponins - chemistry; Saponins - pharmacology; Structure-Activity Relationship; structure-activity relationships; Triterpenes - chemical synthesis; Triterpenes - chemistry; Triterpenes - pharmacology; triterpenoid saponins
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np800579x

The naturally occurring cytotoxic saponin 28-O-β-d-glucopyranosylbetulinic acid 3β-O-α-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, and PC-3 human cancer cell lines, the bidesmosidic betulin saponin 22a, bearing α-l-rhamnopyranoside moieties at both C-3 and C-28 positions, was determined to be a potent cytotoxic agent (IC50 1.8−1.9 μM).