Selective Epimerisation of a Fungal Cyclopeptolide via an 2-Amino-oxazole Intermediate - Conformational Consequences

The selective epimerisation of the cyclic depsiheptapeptide (cyclopeptolide HUN-7293) 1 at a single amino acid (Leu5) was achieved in four steps. A regio-selective thionation at one of its six amide-bonds provided the corresponding thioamide 2, which upon S-benzylation followed by an unusual silver-promoted intra-molecular cyclisation, was converted to the 2- aminooxazole derivative 4. Re-opening of the oxazole ring by acid hydrolysis regenerated the cyclopeptolide, but preferentially with inverted stereochemistry at Leu5 5. The influence of this inversion on the backbone conformation is discussed