Piperazine-2,3,5-triones in the synthesis of constrained peptides

Abstract

Amino acid amides react with diethyl oxalate and sodium ethoxide to yield 6-substituted piperazine-2,3,5-triones, which can be mono-alkylated at N4, bis-alkylated at N4 and C6, or tris-alkylated at N4, N1, and C6 under mild basic conditions; this provides access to i) α,α-disubstituted cyclic peptide derivatives; ii) constrained peptides via C(α)N bond formation; iii) DKP analogues.