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Silanol: a bifunctional group for peptide synthesis and late-stage functionalization.

ABSTRACT: Chemical modification of a specific amino acid residue on peptides represents an efficient strategy to improve their pharmacokinetics and facilitates the potential to achieve post-synthetic diversification of peptides. Herein, we reported the first Pd-catalyzed late-stage ortho-olefination of Tyr residues on peptides with high chemo- and site-selectivity, by employing the easily attached and removable silanol as a bifunctional protecting group and directing group. Up to hexapeptides with variation on amino acid sequences or locations of the Tyr residue and different olefins were compatible with this protocol, which enriched the chemical toolbox for late-stage modification via C(sp²)-H functionalization. Furthermore, the orthogonal protection strategies of Tyr were also developed and could be applied to SPPS.

SUBMITTER: Hu QL

PROVIDER: S-EPMC8159358 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Silanol: a bifunctional group for peptide synthesis and late-stage functionalization.

Hu Qi-Long QL Hou Ke-Qiang KQ Li Jian J Ge Yang Y Song Zhen-Dong ZD Chan Albert S C ASC Xiong Xiao-Feng XF

Chemical science 20200603 23

Chemical modification of a specific amino acid residue on peptides represents an efficient strategy to improve their pharmacokinetics and facilitates the potential to achieve post-synthetic diversification of peptides. Herein, we reported the first Pd-catalyzed late-stage <i>ortho</i>-olefination of Tyr residues on peptides with high chemo- and site-selectivity, by employing the easily attached and removable silanol as a bifunctional protecting group and directing group. Up to hexapeptides with ...[more]

PMID: 34094099

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