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A concise synthesis of 28a-homolupane triterpenes and the corresponding saponins containing d -mannose, d -idose, d -arabinose, and l -rhamnose moieties was elaborated. The overall synthesis of the new triterpenes involved three linear steps starting from readily available 3-O-acetyl-betulinal: elongation of the carbon chain by Wittig reaction followed by enol ether hydrolysis and reduction (or oxidation) of the elongated aldehyde. Saponins were obtained by glycosylation of triterpenes with classical Schmidt donors. Cytotoxic activities of new lupane and homolupane compounds were evaluated in vitro. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. Influence of the side-chain structure and substituents on the cytotoxicity of betulin and homobetulin derivatives was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer compounds.

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing d -mannose, l -arabinose, and l -rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.