Solid-Phase Synthesis of Substituted 2,3-Diketopiperazines from Reduced Polyamides

An efficient method for the solid phase synthesis of 1,6-disubstituted 2,3-diketopiperazine and 1,4,5-trisubstituted 2,3-diketopiperazine derivatives is described. The reduction of resin-bound acylated amino acids or resin-bound acylated dipeptides, followed by treatment with oxalyldiimidazole, affords the corresponding diketopiperazines in good yield and high purity. This is an example of a broader approach to the solid phase synthesis of individual heterocyclic compounds using peptides directly or indirectly as starting materials.