Piperazirum, a new biologically active alkaloid isolated from Arum palaestinum Bioss, is described, starting from commercially available α-amino acids. Two synthetic strategies were developed for the synthesis of the enantiomeric pair of compounds corresponding to the proposed structure of piperazirum. The first strategy was used in the synthesis of stereoisomers, and the second one was used in generating the analogues. The compounds synthesized were screened against different cell lines to evaluate their cytotoxicity profiles. Piperazirum, its stereoisomers, and its analogues were synthesized and tested for their antiproliferative activity. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.