Synthesis of Fluorescent Lanthipeptide Cytolysin S Analogues by Late-Stage Sulfamidate Ring Opening

Nucleophilic ring opening of cyclic sulfamidates derived from amino acids is a common strategy for the synthesis of lanthionine derivatives. In this work, we report the regio-, chemo-, and stereoselective intramolecular S-alkylation of a cysteine residue with N-sulfonyl sulfamidates for the synthesis of cyclic lanthionine-containing peptides. The strategy involves the solid-phase synthesis of sulfamidate-containing peptides followed by late-stage intra-molecular cyclization. This protocol allowed for the synthesis of four full-length cytolysin S (CylLS '') analogues, two alpha-peptides and two hybrid alpha/beta-peptides. Their conformational preferences and bio-logical activities were assessed and compared with those of wild-type CylLS '' .