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

Abstract

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.

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

“…Unnatural heteroarene amino acids have also been widely used as building blocks to prepare various heterocyclic peptides [17][18][19][20][21][22]. In particular, 1,2-oxazole amino acid derivatives, such as compounds V [20], VI [21], and VII, VIII [22], can be easily synthesized and are suitable for insertion with the corresponding heterocycle into a peptide-like structure.…”