Solid phase synthesis of 1-substituted pyroglutamates

Starting from a dipeptide containing the tBu ester of glutamic acid, disubstituted 2-pyrrolidinones were prepared in good yield and high purity. Cyclization takes place using DPPA as activating reagent. Diversity was achieved through reductive alkylation of the starting dipeptide and N-alkylation following the cyclization step. This approach has been used for the synthesis of both individual compounds and mixture-based combinatorial libraries.