Total synthesis and biological evaluation of PF1171A, C, F, and G, cyclic hexapeptides with insecticidal activity

The total synthesis of the cyclic hexapeptides PF1171A, C, F, and G has been achieved by solid-phase synthesis of a linear precursor and solution-phase macrolactamization. The synthesis includes a solid-phase peptide coupling with the weakly nucleophilic amino group of an anthranilic acid residue. This was efficiently achieved by in situ generation of an Fmoc-amino acid chloride using triphosgene. The natural products exhibit potent paralytic activities against silkworm larvae, whereas epi-PF1171A and epi-PF1171C, bearing l-Ala instead of d-Ala, were relatively inactive. X-ray crystallographic analysis indicates that intramolecular hydrogen bonds in PF1171 peptides are critical for maintaining their active conformations.