Unified total synthesis of colisporifungin, ophiotine and verruculin

The total synthesis of colisporifungin, ophiotine and verruculin, possessing a common cyclic lipohexadepsipeptide framework including three D-amino acids and β-alanine, was successfully achieved by a unified, convergent route based on solution-phase peptide synthesis. The framework was assembled from a tripeptide fragment and a lipotridepsipeptide segment by a connection/cyclization process at the final stage, where a ring-forming condensation between the less-hindered β-alanine and the L-threonine residues effectively occurred. Initial introduction of the fatty acid moiety to D-glutamine to avoid unnecessary protecting group manipulations was also helpful for making the synthesis concise. • The total synthesis of colisporifungin, ophiotine and verruculin was achieved. • A unified, convergent route based on solution-phase peptide synthesis was developed. • Initial installation of the fatty acid moiety made the total synthesis concise.