Microwave assisted synthesis, spectroscopy, crystal structure, characterization and Hirshfeld surface analysis of ureidopeptides and intermediates derived from α,α-dipeptides C-terminal glycine

Abstract

This article describes synthetically useful catabolic pathway activation of the primordial peptide cycle through the effect of microwave irradiation, giving a new variety of peptide derivatives: the α,α-ureidopeptides, as 1,3-disubstituted unsymmetrical ureas via hydantoin, starting from NCbz protected α,α-dipeptide methyl esters containing glycine as the C-terminal residue. The new ureidopeptide series were synthesized and structurally characterized by FT-IR, MS, 1H NMR, 13C NMR spectroscopy, and single-crystal X-ray diffraction analysis. Molecular structure and crystal packing of Phe-Gly-ureidopeptide 3h noted C12H14N2O5, in a monoclinic system and C2/c space group with parameters a = 32.42 Å, b = 9.62 Å, c = 8.40 Å, β=103.25°, and Z = 8, Z’=1, confirm assignations evaluated for the new compounds. The procedure has been extended to the isolation of the α,α-ureidopeptide intermediate, the hydantoin Leu-Gly 4e, C9H14N2O4, demonstrating the synthetic mechanism and crystallized in an orthorhombic system, Pbca space group, with parameters a = 5.19 Å, b = 11.49 Å, c = 35.99 Å, α=β=γ=90°, and Z = 8, Z’=2. Hirshfeld surface analysis on crystal structures of both ureic-derivatives revealed crystal packing relevance and stabilization by the competition of predominant supramolecular interactions easily discernible as nonconventional intermolecular CH•••π, and classical NH•••O or C = OOH•••O = COH, forming complex hydrogen bonding patterns.