Chemoselective Peptide Backbone Diversification and Bioorthogonal Ligation by Ruthenium‐Catalyzed C−H Activation/Annulation. Issue 13 (7th May 2021)

• Record Type: Journal Article
• Authors: Song, Liangliang; Ojeda‐Carralero, Gerardo M.; Parmar, Divyaakshar; González‐Martínez, David A.; Van Meervelt, Luc; Van der Eycken, Johan; Goeman, Jan; Rivera, Daniel G.; Van der Eycken, Erik V.
• Is Part Of: Advanced synthesis & catalysis. Volume 363:Issue 13(2021)
• Page Start: 3297
• Page End: 3304
• Publication Date: 2021-05-07
• Subjects: Peptides -- C−H Activation -- Metal catalysis -- Ruthenium -- Annulation; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.202100323
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: The field of peptide derivatization by metal‐catalyzed C−H activation has been mostly directed to modify the side chains, but poor attention has been given to the peptide backbone. Here we report a ruthenium‐catalyzed C−H activation/annulation process that can chemoselectively modify the peptide backbone producing functionalized isoquinolone scaffolds with high regioselectivity in a rapid and step‐economical manner. This strategy is characterized by racemization‐free conditions and the production of fluorescent peptides, and peptide conjugates to drugs, natural products and other peptide fragments, providing a chemical approach for the construction of novel peptide‐pharmacophore conjugates. Mechanistic studies suggest that amide bonds of peptide backbone act as the bidentate directing group to promote the C−H activation/annulation process. This report provides an unprecedented example of peptide backbone diversification and bioorthogonal ligation exploiting the power of ruthenium‐catalyzed C−H activation. Abstract :