Research ArticleChemistry

Macrocyclization of peptidoarylacetamides with self-assembly properties through late-stage palladium-catalyzed C(sp2)▬H olefination

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Science Advances  08 Mar 2019:
Vol. 5, no. 3, eaaw0323
DOI: 10.1126/sciadv.aaw0323

Abstract

Peptide macrocycles often display diverse bioactivities and self-assembly properties, which lead to a variety of applications in medicinal and material sciences. Transition metal–catalyzed C▬H activations are emerging strategies for site-selective functionalization of amino acids and peptides, as well as the construction of cyclic peptides. Here, we report the development of a peptide-directed method for the macrocyclization of peptidoarylacetamides by Pd(II)-catalyzed late-stage C(sp2)▬H olefination. In this protocol, peptide backbones act as internal directing groups and enable facile preparation of diverse cyclic peptides that are difficult to synthesize by conventional macrolactamization. Furthermore, we show that the incorporation of aryl-alkene cross-link in the backbone constrains cyclic peptides into conformations for self-assembly.

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