Dipeptide vinyl sultams: Synthesis via the Wittig–Horner reaction and activity against papain, falcipain-2 and Plasmodium falciparum

Vinyl sultams were prepared via the Wittig–Horner reaction and revealed to be active against recombinant falcipain-2 and Plasmodium falciparum W2. The synthesis of phosphonate derivatives of N-phenyl- and N-benzyl-γ- and δ-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 μM. In contrast, vinyl sultams demonstrated weak activity against recombinant falcipain-2 and Plasmodium falciparum W2.