Total synthesis of an antifungal cyclic depsipeptide aureobasidin A

Abstract The first total synthesis of antifungal cyclic depsipeptide aureobasidin A is described. The synthesis was achieved mainly using bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) as a coupling reagent. Peptide cyclization was carried out between L- allo -isoleucine (L- a lle 1 ) and L- Pro 9 residues in the linear nonapeptide at the final step of the synthesis. Synthesized aureobasidin A was completely identical with the natural antibiotic with respect to antifungal activity and physicochemical properties. Unusual reactions due to N -methylamino acid, an oxazoline-mediated reaction and an N , O -acyl migration, are also described.