Solid‐Phase Synthesis of Phosphoramidate‐Linked Glycopeptides

Abstract

The synthesis of stable glycopeptide mimetics is of particular interest in bioorganic chemistry to allow access of glycoconjugates for biological investigations. In this paper, a straightforward solid‐phase synthesis of a novel glycopeptide mimetic by a Staudinger phosphite reaction is presented. Thereby, a dimethyl phosphite containing peptide, which is obtained by standard phosphitylation of a Ser residue, is treated on the solid support with glycosyl azides, delivering phosphoramidate‐linked glycoconjugates. These artificial glycopeptides show excellent stability under acidic and physiological conditions.

Staudinger Ligation as a Method for Bioconjugation

“…[113] This method was extended towards the synthesis of phosphoramidate-linked glycopeptides. [114] The strategy involved a two-step approach in which serine-containing peptides were first converted into phosphite peptides by phosphitylation with phosphoramidites. In a second step the phosphite peptides were treated with glycosylazides, thereby generating phosphoramidate-linked glycopeptides.…”

Staudinger‐Ligation als Methode zur Biokonjugation

“…Dieselbe Arbeitsgruppe verwendete die Staudinger‐Phosphit‐Methode zur Festphasensynthese Phosphoramidat‐haltiger Peptide 113. Diese Methode wurde auf die Synthese Phosphoramidat‐verknüpfter Glycopeptide ausgedehnt 114. In einer zweistufigen Synthesestrategie wurden zunächst Serin enthaltende Peptide durch Phosphitylierung mit Phosphoramiditen in Phosphitpeptide überführt.…”

Recent Advances in the Synthesis of Carbohydrate Mimetics

“…65 An access to a very special case of N-glycosidic linkages was presented in 2010 by Hackenberger and co-workers. 66 They synthesized phosphoramidate-linked glycopeptides by a Staudinger-phosphite reaction on solid support. The key step of the sequence is the phosphitylation of an unprotected serine residue 113 incorporated in a peptide chain to form the dimethylphosphite-containing peptide 114.…”