Regioselective Solid-Phase Synthesis of Peptide Analogues Containing 3,4- or 3,5-Disubstituted Isoxazole as s-cis or s-trans Peptide Bond Mimics

Pierrick Bruyat (1) , Ludovic Jean (1) , Pierre-Yves Renard (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

Improved conditions for the synthesis of 3,5‐disubstituted isoxazoles (mimicking the s‐trans peptide bond) without a metal catalyst were implemented. New conditions allowing for the synthesis of 3,4‐disubstituted isoxazoles (mimicking s‐cis peptide bond) using ruthenium catalysts were developed. A method for regioselective solid‐phase synthesis of disubstituted peptidoisoxazoles is reported. Improved conditions for the synthesis of 3,5‐disubstituted isoxazoles (mimicking s‐trans peptide bond) without metal catalysts were implemented. New conditions enabling the synthesis of 3,4‐disubstituted isoxazoles (mimicking s‐cis peptide bond) using ruthenium catalysts were developed. This study provides a means for the regioselective preparation of new libraries of peptidomimetic molecules containing an isoxazole moiety within the backbone.

Domaines: Chimie organique

Pierrick Bruyat, Ludovic Jean, Pierre-Yves Renard. Regioselective Solid-Phase Synthesis of Peptide Analogues Containing 3,4- or 3,5-Disubstituted Isoxazole as s-cis or s-trans Peptide Bond Mimics. European Journal of Organic Chemistry, 2019, 2019 (20), pp.3134-3141. ⟨10.1002/ejoc.201900378⟩. ⟨hal-02319741⟩