N-terminus 4-chloromethyl thiazole peptide as a macrocyclization tool in the synthesis of cyclic peptides: application to the synthesis of conformationally constrained RGD-containing integrin ligands

The synthesis of conformationally constrained RGD-containing integrin ligands via an efficient solid-phase intramolecular thioalkylation reaction is described. The reaction of S-nucleophiles with newly generated N-terminal 4-chloromethyl thiazoles leads to the desired cyclic RGD products 5 in high purities and good overall yields.