A New Approach to Glycopeptides

Abstract

In only three or four steps glycosylated dipeptide and tripeptide fragments, respectively (see scheme), can be obtained from hydroxy amino acids by using a novel protecting group/activation concept. The method presented is even superior to the pentafluorophenyl ester method.

Synthesis of Glycoproteins

“…129 Recently, the glycosylation of hexafluoroacetone-protected hydroxyl-bearing Ser, hydroxy-Pro, and Tyr allowed preparation of glycosylateddipeptides in just three steps from unprotected amino acid, e.g., T[Ac 4 -O-β-Glc]Y in 70% overall yield from T and Y. 130 As yet, no convergent O-glycosylation of a peptide has been shown, and the failure of, for example, pentenyl glycosides in this regard has been noted. 131…”

“…For example, O-glycosylation of Ser or Thr with, for example, a trisaccharide trichloroacetimidate glycosyl donor allows O-linked trisaccharide−amino acid building blocks to be synthesized . Recently, the glycosylation of hexafluoroacetone-protected hydroxyl-bearing Ser, hydroxyPro, and Tyr allowed preparation of glycosylated-dipeptides in just three steps from unprotected amino acid, e.g., T[Ac 4 - O -β-Glc]Y in 70% overall yield from T and Y . As yet, no convergent O-glycosylation of a peptide has been shown, and the failure of, for example, pentenyl glycosides in this regard has been noted …”

Synthesis of Pseudopeptides with Sulfoximines as Chiral Backbone Modifying Elements

“…In general, the following modifications can be carried out on any part of a peptide and they can be applied in any combination: [3±6] amino acids can be deleted, or added/replaced; [7] short- [8] or longrange cyclizations [9] can be used; the bonds of the peptide backbone can be substituted by surrogates; [5] the backbone can be replaced totally by a novel scaffold [1b, 10] or, to achieve a higher bioavailability the peptides can be glycosylated. [11] Most modifications have been made on the amide linkage because it is the primary target for enzymatic degradation, and hence the metabolic stability of the peptides can be increased. [3,12] Lucente [13] and Liskamp [14] have reported on the synthesis of derivatives with sulfinamide or sulfonamide moieties as tetrahedral transition state analogues for the hydrolysis of the amide bond.…”

Glycosylated neuropeptides: A new vista for neuropsychopharmacology?

“…The synthesis of glycopeptides still poses significant synthetic challenges, particularly in large scale. 83 There are now several methods available to prepare N-linked or O-linked glycosylated amino acids. This subject has been reviewed recently.…”