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A Highly Convergent Total Synthetic Route to Glycopeptides Carrying a High‐Mannose Core Pentasaccharide Domain N ‐linked to a Natural Peptide Motif
Author(s) -
Danishefsky Samuel J.,
Hu Shuanghua,
Cirillo Pier F.,
Eckhardt Matthias,
Seeberger Peter H.
Publication year - 1997
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.19970031011
Subject(s) - glycopeptide , chemistry , mannose , glycal , anomer , residue (chemistry) , asparagine , stereochemistry , aspartic acid , peptide , convergent synthesis , combinatorial chemistry , organic chemistry , amino acid , biochemistry , stereoselectivity , catalysis , antibiotics
N ‐Linked glycopeptides were synthesized by condensation of a highmannose anomeric amine bearing a pentasaccharide with aspartic‐acid‐containing tri‐ and pentapeptides through the agency of IIDQ. The pentasaccharide portion, corresponding to the „core” region of all asparagine‐linked glycoproteins, was assembled by means of glycal‐derived thioethyl donors and glycal acceptors. The central mannose residue was established by inversion of the C2 hydroxyl of a glucosyl precursor in the pentasaccharide. The protecting‐group scheme employed allows the extension of the pentasaccharide through the terminal mannose units. While a fully convergent coupling of the high‐mannose carbohydrate to the peptide domain has thus been accomplished for the first time with a fully synthetic sugar, the stereochemical integrity of the anomeric center of the carbohydrate domain was not maintained and a mixture of glycopeptides was obtained.