The synthesis of phosphonate derivatives of N-phenyl- and N-benzyl-gamma and delta-sultams, and their application in the Wittig-Horner reaction with N-BOC-L-phenylalanine aldehyde to afford E- and Z-isomers, are described. These compounds were further processed to provide five dipeptide vinyl sultams, which were found to be inactive against papain at concentrations up to 50 mu M. In contrast, vinyl sultams demonstrated weak activity against recombinant falcipain-2 and Plasmodium falciparum W2. (c) 2006 Elsevier Ltd. All rights reserved.