title: Synthesis and alkylation of aza-glycinyl dipeptide building blocks.
abstract: Aza-glycinyl dipeptides are useful building blocks for the synthesis of a diverse array of azapeptides. The construction of the aza-glycine residue is however challenging, because of the potential for side reactions, such as those leading to formation of oxadiazalone, hydantoin and symmetric urea by-products. Employing N,N'-disuccinimidyl carbonate to activate benzophenone hydrazone, we have developed a more efficient approach for the synthesis of aza-glycinyl dipeptides. Alkylation of the semicarbazone of the resulting protected aza-glycinyl dipeptides using tetraethylammonium hydroxide and propargyl bromide provided an efficient entry into the aza-propargylglycinyl peptide building blocks, which have served previously in various reactions including Sonogashira cross-couplings, dipolar cycloadditions and intramolecular exo-dig cycloadditions to furnish a variety of azapeptide building blocks.
authors.affiliation: Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montreal, Quebec, H3C 3J7, Canada.
authors.forename: Yesica
authors.initials: Y
authors.lastname: Garcia-Ramos
authors.forename: William D
authors.initials: WD
authors.lastname: Lubell
mesh_terms: D000478:Alkylation; D001372:Aza Compounds / Q000737:chemistry*; D061565:Cycloaddition Reaction; D004151:Dipeptides / Q000138:chemical synthesis*; D005998:Glycine / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis; D013388:Succinimides / Q000737:chemistry
chemical_list: D001372:Aza Compounds; D004151:Dipeptides; D010455:Peptides; D013388:Succinimides; D005998:Glycine
keywords: N,N′-disuccinimidyl carbonate (DSC); alkylation; aza-glycinyl dipeptide; azapeptide; benzophenone hydrazone