Total synthesis of the macrocyclic peptide stylopeptide II using oxime resin

Abstract

We report the first total synthesis of the macrocyclic decapeptide stylopeptide II (1), which was isolated from the Papua New Guinea marine sponge of the Hymeniacidon genus (formerly Stylotella sp). The methodology to synthesize this compound exploitsthe oxime resin as solid support and is highly efficient allowing the preparation of the macrocyclic decapeptide without a chromatographic purification step. Notably, stylopeptide II (1) was rapidly prepared at gram-scale without any detectable amounts of undesired side products that could have arisen from the coupling, deprotection, cyclization, epimerization and dimerization reactions. The methology is general and accelerates the large-scale synthesis of macrocyclic peptides.