SYNTHESIS OF 1,2,4-OXADIAZOLE-DERIVED, 1,3,4-OXADIAZOLE-DERIVED, AND 1,2,4-TRIAZOLE-DERIVED DIPEPTIDOMIMETICS

Three series of heterocyclic dipeptidomimetics have been synthesized. The compounds were designed as amino acid-glycine mimetics containing 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,4-triazole ring systems, useful as building blocks in the synthesis of modified peptides. The heterocyclic moieties were chosen according to their geometrical, electrostatical, and hydrogen bonding properties together with the synthetic accessibility. The syntheses started with Boc-protected L-amino acids (Ala, Gly, Asp, Phe, Ser, Arg, Cys, and Pro), and the reaction conditions were chosen to allow for the formation of products with high enantiopurity. The enantiomeric excess was determined by HPLC using chiral stationary phases.