Solid-Phase Synthesis of Peptides Containing Reverse-Turn Mimetic Bicyclic Lactams

The solid-phase synthesis and characterization of a series of peptides (4–15) containing reverse-turn mimetic bicyclic lactams is reported. The bicyclic lactams (1a, 1b) possess high structural similarity to the two central residues of a β-turn. Amino acid conjugates of these bicyclic lactams were synthesized on solid supports following a 9-fluorenylmethoxycarbonyl (FMOC) protection strategy on Wang-Merrifield resin. Coupling between amino acids was accomplished by means of diisopropylcarbodiimide (DIC)/hydroxyazabenzotriazole (HOAt). Coupling between amino acids and the mimics was performed with the potent Carpino's reagent O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU). The final compounds were cleaved from the resin and obtained as N-acetylated methyl esters or benzyl amides.