Late stage modification of peptides via CH activation reactions

• Published in: Tetrahedron letters Vol. 58; no. 14; pp. 1357 - 1372
• Main Authors: Sengupta, Saumitra, Mehta, Goverdhan
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 05.04.2017
• Subjects: Amino acid; C[sbnd]H activation; Late stage modification; Peptide modification; Protein; Late stage modification; Amino acid; CH activation; Peptide modification; Protein
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2017.02.069

[Display omitted] •Advances in post synthetic peptide modification via CH activation are highlighted.•Site selective CH functionalization of non-polar amino acids in peptides reviewed.•Biaryl stapled peptide synthesis via CH activation is described.•Diversity oriented modifications of cyclopeptides via CH activation exemplified. Recently developed strategies for late stage modification of peptides through CH activation, an arena of contemporary interest in chemical biology and drug discovery, are discussed. Through this tactic, non-polar amino acids in peptides have been selectively functionalized and CH activation enabled new CC and CX bond formations (arylation, alkynylation, fluorination, hydroxylation, azidation, etc.) are documented. Significant advances have been made in Pd or Au-catalyzed, racemization-free, tryptophan specific modifications of large peptides via CH arylation and alkynylation reactions without any protecting group requirement. Development of a new biaryl stapling technique for complex peptides, 18F radiofluorine introduction and diversity oriented post synthetic applications on bio-active cyclopeptides like valinomycin and aureobasidin are additional highlights which underscores the vast potential of late stage CH activation reactions in peptide based therapeutics research.