Cyclopeptides from the Mushroom Pathogen Fungus .

Three new cyclopeptides with serial Phe residues were identified with the aid of HPLC-DAD analysis, from the culture broth of , a fungal pathogen causing mushroom cobweb disease. Cladoamides A () and B () have two consecutive -methylphenylalanine units in the destruxin class cyclic depsipentapeptide framework, while cladoamide C () has a three consecutive Phe motif in a cyclopentapeptide structure. Of these three cyclopeptides, showed potent autophagy-inducing activity at 10 μg/mL, comparable to a positive control, rapamycin. For the determination of the absolute configurations of the Ile residues in and , new conditions for separating Ile and -Ile, using a pentafluorophenyl-bonded solid phase and methanolic solvent, were established within the analytical scheme of the advanced Marfey's method, thus offering a convenient alternative to the C Marfey's method, which requires elution with a three-solvent mixture. The sequence of two d-Phe and one l-Phe in was determined through NMR chemical shift prediction by DFT-based calculations and chemical synthesis, which demonstrated the significance of noncovalent interactions in the accurate calculation of stable conformers for peptides with multiple aromatic rings.