1124196-12-8Relevant articles and documents
Synthesis of small glycopeptides by decarboxylative condensation and insight into the reaction mechanism
Sanki, Aditya K.,Talan, Rommel S.,Sucheck, Steven J.
experimental part, p. 1886 - 1896 (2009/08/07)
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 α-ketoacid moiety at the C-terminus, were synthesized and ligated with a series of O-iert-butyl-proteeted N-hydroxylamino acids to afford O-tert-butyl-proteeted 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 α-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 O18-labeled phenyl pyruvic acid and N-hydroxyphenethylamine oxalate salt resulted in amide products lacking the O18-label, providing further support for the nitrilium ion in the reaction pathway.
