Novel betulin derivatives were prepared and tested for their antitumor activity. Starting from 3-O-acetyl- or 3-O-methyl-betulinic aldehyde, the synthesis of C-28 ethynyl derivatives was performed; their subsequent transformation with several 1,3-dipolarophiles afforded pyrazoles and 1,2,3-triazoles. Their screening for antitumor activity was performed in a panel of 15 human cancer cell lines by a colorimetric SRB-assay. Thereby, several compounds revealed a higher cytotoxicity than betulinic acid. In addition, the encapsulation of the lead structure 7 into liposomes was investigated. The results from a dye exclusion test and from DNA laddering experiments provided evidence for an apoptotic cell death.