Bioinspired Diversification of Short Peptides via Tyrosine Umpolung

2026/02/09 by Srashti Chaudhary, Hülya Aldemir, Stefan F. Kirsch +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · #Chemical Synthesis and Analysis #Click Chemistry and Applications #Oxidative Organic Chemistry Reactions

paper · pdf · doi:10.26434/chemrxiv.10002038/v1

openalex publication_date 2026/02/09 · openalex created_date 2026/02/10 · openalex updated_date 2026/07/14

Abstract

Herein, we report a bioinspired strategy for the selective modification of tyrosine residues in short peptides based on a formal umpolung of the phenolic side chain. Mild oxidation with a hypervalent iodine(V) reagent enables the in situ generation of ortho-quinone intermediates, effecting a polarity inversion. These electrophilic intermediates can be selectively intercepted by external nucleophiles, enabling diversification of tyrosine residues either through skeletal modification of the phenolic core into phenazine scaffolds, or via peripheral modifications through the formation of tyrosine-cysteine cross-links.

Discussions

• Our first venture into short peptide diversification is now online 😁 doi.org/10.26434/che... [bsky, 4 points, 1 comments]

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