Total Synthesis of Piperazimycin A: A Cytotoxic Cyclic Hexadepsipeptide

The first total synthesis of piperazimycin A is disclosed, an 18-membered macrocycle which is composed of a hydroxyacetic acid and five rare amino acids and carries out the macrocyclization through an ester bond formation.

Abstract

Pied piper: The first total synthesis of the title compound 1, a potent cytotoxic natural product has been achieved. The key elements include an efficient synthesis of the difficult-to-install (R,S)-γClPip/(S,S)-γOHPip dipeptide fragment as well as macrocyclization by an SN2 reaction of an N-2-chloroacetyl moiety with a carboxylate anion.