First total synthesis of hormaomycin, a naturally occurring depsipeptide with interesting biological activities.

Some unique features were disclosed during the structure elucidation of the cyclic depsipeptide hormaomycin (1), first isolated in 1989 from a Streptomyces griseoflavus strain and found to have quite an interesting spectrum of biological activities. Besides one residue of the proteinogenic amino acid isoleucine [(S)-Ile], it contains two units of 3-methylphenylalanine [(betaMe)Phe], one of (2R)-allo-threonine [a-Thr] as well as two moieties of 3-(trans-2-nitrocyclopropyl)alanine [(3-Ncp)Ala] and one of 4-(Z)-propenylproline [(4-PE)Pro]. The latter two have never been found in any natural product before. The side chain of 1 is terminated with the residue of 5-chloro-1-hydroxypyrrole-2-carboxylic acid [Chpca]. This first synthetic access to hormaomycin 1 will make it possible to prepare structural analogues of this interesting natural depsipeptide in order to elucidate structure-activity relationships and the biologically active minimal unit.