Synthetic studies on antifungal cyclic peptides, echinocandins. Stereoselective total synthesis of echinocandin D via a novel peptide coupling

Abstract

Synthetic studies on the novel fungicidal oligopeptides, echinocandins ( 1b and 1c), are described. The constituent amino acids 5–8 were synthesized in a stereocontrolled manner from the chiral starting materials, 5a, 6a and 7a, respectively. The coupling of these amino acids was characterized by the use of unprotected amino acid as the C-terminal and 2-pyridyl thiol ester as the N-terminal, and the coupling was performed in the presence of 1-(trimethylsilyl)imidazole (TMSIm) or a catalytic amount of tert-amine to give C-terminal free dipeptides, 14 and 16a, respectively, which were converted to the pentapeptide 17a, a common intermediate for the synthesis of 1b and 1c. The synthesis of 1c was achieved by the cyclization of the hexapeptide 24b.