Studies on the biosynthesis of chetomin: enantiospecific synthesis of a putative, late-stage biosynthetic intermediate

The enantiospecific synthesis of desthiochetomin, a putative biosynthetic intermediate of the epidithiodioxopiperazine natural product chetomin, is described. A diastereoselective N-alkylation was employed to form the key C3-N1′ bond of the heterodimeric indoline core, followed by peptide coupling and dioxopiperazine cyclization with the requisite N-methyl amino acids. A related sarcosine-derived dioxopiperazine was prepared in the same manner. The first proposed biosynthesis of chetomin is also detailed in the text.