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C ‐Glycosyl Amino Acids through Hydroboration–Cross‐Coupling of exo ‐Glycals and Their Application in Automated Solid‐Phase Synthesis
Author(s) -
Koch Stefan,
Schollmeyer Dieter,
Löwe Holger,
Kunz Horst
Publication year - 2013
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.201300150
Subject(s) - glycosyl , glycopeptide , chemistry , glycosidic bond , glycosylation , amino acid , hydroboration , stereochemistry , threonine , combinatorial chemistry , biochemistry , phosphorylation , serine , catalysis , enzyme , antibiotics
Abstract O ‐Glycosylation is one of the most important post‐translational modifications of proteins. The attachment of carbohydrates to the peptide backbone influences the conformation as well as the solubility of the conjugates and can even be essential for binding to specific ligands in cell–cell interactions or for active transport over membranes. This makes glycopeptides an interesting class of compounds for medical applications. To enhance the long‐term availability of these molecules in vivo, the stabilization of the glycosidic bond between the amino acid residue and the carbohydrate is of interest. The described modular approach affords β‐linked C ‐glycosyl amino acids by a sequence of Petasis olefination of glyconolactones, stereoselective hydroboration and a mild B‐alkyl‐Suzuki coupling reaction. The coupling products were transformed to C ‐glycosyl amino acid building‐blocks suitable for solid‐phase synthesis and successfully incorporated into a partial sequence of the tumor‐associated MUC1‐glycopeptide. The resulting C ‐glycopeptides are candidates for the development of long‐term stable mimics of O ‐glycopeptide vaccines.