Both D-phenylalanine and Proline Keep the Type II' β-turn During Thermocyclization of Linear Gramicidin S Precursor Analogues

The synthesis and thermocyclization of linear Gramicidin S precursor analogues (LGSA) were presented. CD spectra suggested that synthesized LGSA adopt a pleated β-sheet structure that is stabilized by intramolecular hydrogen bonds. Both Dphe6 and Pro7 residues were found to play an important role in maintaining the β-sheet conformation of LGSA. Our results indicate that unactivited LGSA, with the preorganized β-sheet structure, can be efficiently cyclized into the corresponding head-to-tail cyclic products in high yield after being heated under solvent-free conditions.