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. 2020 Oct 6;11(42):11531-11538.
doi: 10.1039/d0sc03791e.

Site-selective aqueous C-H acylation of tyrosine-containing oligopeptides with aldehydes

Marcos San Segundo  1 , Arkaitz Correa  1
Affiliations

Site-selective aqueous C-H acylation of tyrosine-containing oligopeptides with aldehydes

Marcos San Segundo et al. Chem Sci. .

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.

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Conflict of interest statement

A patent disclosing the Pd-catalyzed aqueous acylation of Tyr-containing oligopetides has been filed (P202030131, Spain).

Figures

Fig. 1
Fig. 1. Illustrative Tyr-containing biologically relevant polypeptides.
Scheme 1
Scheme 1. Ortho C–H functionalization of Tyr derivatives.
Scheme 2
Scheme 2. Consecutive C(sp2)–H aroylation reaction.
Scheme 3
Scheme 3. Reductive cleavage of the DG.
See this image and copyright information in PMC

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