Peptide phenyl thioesters are particularly reactive starting materials for Native Chemical Ligation.  Here we present a new photochemical method for the synthesis of peptide phenyl thioesters under neutral reaction conditions with various C-terminal amino acids.  The photoreactive peptides are synthesized by Fmoc strategy on the solid support with a photoreactive nitroindoline linker.  After cleavage of the photoreactive and fully protected peptide from the beads an auxiliary nucleophile such as N-hydroxybenzyltriazole or N-hydroxysuccinimide is used to photochemically generate the activated peptide thioester in situ.  Then thiophenol is introduced in the dark. This new method enables us to synthesize peptide phenylthioesters up to 21 amino acids long in good to high yields, and with less than 1% epimerization at the C-terminal.

Synthesis of peptide phenyl thioesters using a solid support with a photoreactive nitroindoline linker

246th National Meeting (2013)

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