Peptido-organic Diels–Alder reactions on hydrophilic resin: scope for combinatorial chemistry

Abstract

A simple route to activated dienes generated from enone precursors at the N-terminal of immobilised dipeptides is described. The dienes are subjected to reaction with a maleimide dieneophile containing a protected amino functionality for continued peptide synthesis. The reactions are pure and quantitative with dienes generated at the N-terminal of a variety of different dipeptides, including substrates containing amino acids with protected sidechain functionalities. In the work presented, hydrophilic POEPOP resin is used as a solid support. Also described in this paper is a high-yielding method for functional-group exchange of resin hydroxylic functionalities into azido groups via a Mitsunobu reaction, followed by reduction to yield amino-functionalised POEPOP.