Aldehyde Capture Ligation without Involving a Side Chain Functional Group

A potentially general aldehyde capture peptide ligation method was developed. In this method, the salicylaldehyde group in the first ligation partner condenses with the N-terminal amine of the second ligation partner, and an N-hydroxyl elaborately installed on its first peptide bond facilitates the in situ formation of a 1,2,5-oxadiazinane ring. Subsequent O,N-acyl transfer leads to a tertiary amide linkage between the two ligation partners. Concurrent cleavage of the N-O and benzylic C-N bonds by SmI₂ affords a native peptide as the final product. By enebling the method to proceed independently of side-chain functional groups, N-hydroxyl auxiliary group endows a general ligation junction. The broad scope of this ligation method was exemplified by a range of peptide substrates.