The disclosed embodiments detail improved methods for the synthesis of
diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-
diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an
amino acid in the presence of a catalyst in an
organic solvent. The catalyst is selected from the group comprising
sulfuric acid,
phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride,
tributyl phosphate, phenyl phosphonic acid and phosphorous
pentoxide among others. The
solvent is selected from the group comprising:
dimethylacetamide, N-methyl-2-pyrrolidone,
diglyme, ethyl glyme, proglyme, ethyldiglyme, m-
cresol, p-
cresol, o-
cresol, xylenes,
ethylene glycol and
phenol among others.