Preparation of Peptide Selenoesters from Their Corresponding Acyl Hydrazides†

Abstract

Main observation and conclusionSelenoesters are useful substitutes for traditional thioesters in protein ligation chemistry due to their high reactivity in the trans‐thio/selenoesterification reaction. However, existing synthetic routes to access peptide selenoester require a selenoesterification reaction between a selenide and a protected peptide with a free carboxylate at the C‐terminus. Herein, we introduce an efficient method to convert peptide acyl hydrazide, a convenient thioester surrogate, into the desired selenoester for peptide ligation. Our methodology can be applied to fully de‐protected peptides with various C‐terminal amino acid residues in high yield without racemization. We believe that this method provides a useful alternative to access peptide C‐terminal selenoesters for protein ligation.