title: Synthesis of small glycopeptides by decarboxylative condensation and insight into the reaction mechanism.
abstract: The chemical synthesis of homogeneous glycoproteins and glycopeptides facilitates progress toward understanding the functional role of carbohydrates attached to proteins and is important in the preparation of glycopeptide-based therapeutics. A series of protected and unprotected glycosyl dipeptides, glycopeptide I, which contained the alpha-ketoacid moiety at the C-terminus, were synthesized and ligated with a series of O-tert-butyl-protected N-hydroxylamino acids to afford O-tert-butyl-protected glycosyl tripeptides, glycopeptide II. The reactions were carried out under both anhydrous and aqueous conditions at neutral pH to produce glycopeptide products in yields ranging from 15% to 86% depending on the amino acids present at the ligation junction. The best yields were obtained when both the alpha-ketoacid and the N-hydroxylamino acid contained medium-sized side chains. In addition to the expected tripeptide product, 2,5-substituted oxazoles were isolated when O-tert-butyl protected N-hydroxylamines of glycine were employed in the reaction. The formation of the oxazole is believed to result from an intramolecular cyclization of the O-tert-butyl ester on a nitrilium ion intermediate followed by aromatization. A decarboxylative condensation between O(18)-labeled phenyl pyruvic acid and N-hydroxyphenethylamine oxalate salt resulted in amide products lacking the O(18)-label, providing further support for the nitrilium ion in the reaction pathway.
authors.affiliation: Department of Chemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, Ohio 43606, USA.
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Sanki
authors.forename: Rommel S
authors.initials: RS
authors.lastname: Talan
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Sucheck
mesh_terms: D003653:Decarboxylation; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D008970:Molecular Weight; D013237:Stereoisomerism
chemical_list: D006020:Glycopeptides