Controlling the outcome of overacylation of N-protected aminooxyacetic during the synthesis of aminooxy-peptide for chemical ligation

Isidore P. Decostaire (1) , Dominique Lelièvre (1) , Zhang Haihui (1) , Agnès F. Delmas (1)

1 CBM - Centre de biophysique moléculaire

An aminooxy-containing peptide, the nucleophile partner for oxime ligations, is usually grafted on a NH[2]-peptide resin by activating a protected aminooxyacetic acid as an active ester. Here, we have shown that its subsequent coupling to NH[2]-peptide resin competes with the overacylation of the -NH-O- nitrogen and that the overacylation level increases with the basicity of the reaction mixture. Moreover, we found that overacylation is prevented when the COOH of the Aoa-derivatives is engaged in an amide bond.

Mots clés: Aminooxy group; Overacylation; Coupling reagent; Peptide synthesis; Chemoselective ligation

Domaines: Physique [physics]

Isidore P. Decostaire, Dominique Lelièvre, Zhang Haihui, Agnès F. Delmas. Controlling the outcome of overacylation of N-protected aminooxyacetic during the synthesis of aminooxy-peptide for chemical ligation. Tetrahedron Letters, 2006, 47 (39), pp.7057-7060. ⟨10.1016/j.tetlet.2006.07.092⟩. ⟨hal-00168750⟩