Solid-phase synthesis of peptide aldehydes by a Backbone Amide Linker (BAL) strategy

Abstract

C-Terminal peptide aldehydes are potential serine, cysteine and aspartic protease inhibitors, which are emerging as promising therapeutic agents for the treatment of, for example, viral infections [1-4]. There is a need for rapid, efficient, and general solid-phase strategies for synthesis of such compounds. Current methods include release from a Weinreb amide-based handle with from a semicarbazone handle with dilute acid, or from an olefinic linker by ozonolysis [5-7]. Recently, we reported the synthesis of a peptide aldehyde with a C t e rmina l glycinal residue starting from 2,2-dimethoxyethylamine anchored to a BAL handle [8]. Here we report on the extension of this strategy to allow for synthesis of complex peptide aldehydes (Fig. 1).