Site-Selective Epimerization of a Fungal Cyclodepsipeptide via a 5-Aminooxazole Intermediate

The epimerization of the cyclic depsiheptapeptide 1 at a single amino acid (Leu) was achieved in four steps. After regio-selective thionation of 1 at one of its six amide-bonds, subsequent S-benzylation of the thioamide 2 led to the thioimidate 3, which was converted to the peptide-bridged 5-aminooxazole 5 by an unusual mercury promoted intramolecular cyclization. Re-opening of the oxazole ring by acid hydrolysis regenerated the parent cyclopeptolide framework 6, but preferentially with inverted configuration at leucine.