Site-Selective Aqueous C–H Acylation of Tyrosine-Containing Oligopeptides with Aldehydes

Abstract

The development of useful synthetic tools to label amino acids within a peptide framework for the ultimate modification of proteins in a late-stage fashion is a challenging task of utmost importance within chemical biology. Herein, we report the first Pd-catalyzed C–H acylation of a collection of Tyr-containing peptides with aldehydes. This water-compatible tagging technique is distinguished by its site-specificity, scalability and full tolerance of sensitive functional groups. Remarkably, it provides straightforward access to a high number of oligopeptides with altered side-chain topology including mimetics of endomorphin-2 and neuromedin N, thus illustrating its promising perspectives toward the diversification of structurally complex peptides and chemical ligation