Triazene as a Powerful Tool for Solid-Phase Derivatization of Phenylalanine Containing Peptides: Zygosporamide Analogues as a Proof of Concept

Abstract

A novel method for the synthesis of para-substituted phenylalanine containing cyclic peptides is described. The main features of this strategy are the coupling of phenylalanine to the solid support through its side chain via a triazene linkage, on-resin cyclization of the peptide chain, cleavage of the cyclic peptide from the resin under mild acidic conditions and further transformation of the resulting diazonium salt. The usefulness of this approach is exemplified by the solid-phase synthesis of some derivatives of the naturally occurring cyclic depsipeptide zygosporamide.

Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization

“…175 triazene linkage in the first amino acid of the peptidic sequence (74) (Figure 22). 140 However, in some cases, the use of high dilution techniques seems more favorable than this approach, as the removal of the mutual interference of the reactive sites on polymeric matrixes can be incomplete. 141−149 Thus, Malesevic and co-workers compared the preparation of cyclic peptides employing high dilution techniques, using a slow simultaneous addition of the open-chain precursor and the coupling agent, and through an onresin cyclization.…”

“…213 In this regard, many examples in this area involve the use of components containing properly substituted aromatic rings, acetylenic units, and allenic subunits, in particular in connection with the very active area of shape persistent macrocycles (SPMs). 177,214−217 Cammidge and coworkers designed different twinned triphenylenes with a variety of bridging units (140). The different geometry of the bridging units has a direct influence in the overall strain of the macrocyclic product 140 obtained by the reaction of 138 with 139, and accordingly on the strain at the transition state, leading to a successful macrocyclization if the geometry is suitable ( Figure 40).…”

Selective Protection of Secondary Amines as the N-Phenyltriazenes. Application to Aminoglycoside Antibiotics

“…The trisubstituted triazene function has been widely employed in recent years for the protection and/or derivatization of aryl amines, when it is typically introduced by reaction of an arene diazonium salt with either a free or polymer-bound secondary amine . Alternatively, the same trisubstituted triazenes can be employed to protect secondary amines where they display a useful tolerance of a range of oxidizing and reducing conditions yet are readily cleaved on exposure to trifluoroacetic acid .…”

A Comprehensive Review of Bioactive Peptides from Marine Fungi and Their Biological Significance

“…Zygosporium masonii , a marine fungus that produced a cyclic depsipeptide termed zygosporamide ( 131 ) showed potent cytotoxic activity in the NCI’s 60 cell line panel with median GI 50 equal to 9.1 μM. However, it revealed a notable selectivity versus the (Central Nervous System) CNS cancer cell SF-268 with GI 50 equal to 6.5 nM, as well as to the renal cancer cell line RXF 393 showing GI 50 less than 5.0 nM [54,55] (Figure 7).…”