Single-step formation of structurally defined bicyclic peptides via SNAr cyclization

A solid-phase methodology for macrocyclization via an SNAr reaction has bee n developed for the unambiguous formation of bicyclic peptidic compounds in a single cyclization step. The cyclization strategy involves the reaction of a 3,5-dihydroxybenzoyl group with two nitrofluorobenzoyl moieties, The s ymmetry of the dihydroxy aromatic ring results in a single product, and the remaining nitro groups are subsequently reduced to anilines and acylated.