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Efficient Synthesis of S‐Linked Glycopeptides in Aqueous Solution by a Convergent Strategy
Author(s) -
Zhu Xiangming,
Schmidt Richard R.
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305163
Subject(s) - glycopeptide , chemistry , glycan , peptide , yield (engineering) , serine , aqueous solution , glycoprotein , combinatorial chemistry , stereochemistry , chromatography , organic chemistry , biochemistry , materials science , metallurgy , enzyme , antibiotics
In naturally occurring glycopeptides and glycoproteins the glycan residues generally possess N‐ and O‐linkages to the peptide backbone. Here we report the synthesis of the corresponding S ‐ linked glycopeptides by a convergent strategy to provide compounds which should be quite stable to glycosidases. To this end, peptides that contain β‐bromoalanine and γ‐bromohomoalanine were generated either directly by bromination of serine and homoserine residues, respectively, or by standard ligation of the corresponding amino acids. 1‐Thiosugars of O‐acetyl protected GalNAc, GlcNAc, and lactose were prepared by known procedures. Reaction of the thiosugars with these peptides in an ethyl acetate/water two‐phase system, which contained TBAHS and NaHCO 3 , or in a one‐phase system that consists of DMF/water and which contains NaHCO 3 , led to the desired S ‐ linked glycopeptides cleanly and in almost quantitative yield. This reaction also worked well for O‐unprotected 1‐thiosugars.