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

Article abstract of DOI:10.1016/S0040-4039(99)01602-0

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.