Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases

The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner–Wadsworth–Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.

Graphical abstractThe synthesis of dipeptidyl α-fluorovinyl sulfones is described. Inhibitory assays against a Leishmania mexicana cysteine protease revealed low biological activity. Relative rates of Michael additions on vinyl sulfone and α-fluorovinyl sulfone were determined and ab initio calculations on Michael acceptor model structures were performed.Figure optionsDownload full-size imageDownload as PowerPoint slide