title: One-Pot Synthesis of Unprotected Anomeric Glycosyl Thiols in Water for Glycan Ligation Reactions with Highly Functionalized Sugars.
abstract: Chemical synthesis of oligosaccharide conjugates is essential for studying the functional relevance of carbohydrates, and this task would be facilitated considerably if reliable methods for the anomeric ligation of unprotected sugars in water were available. Here, a method for the preparation of anomeric glycosyl thiols from complex unprotected mono-, di-, and oligosaccharides is presented. By exploiting the neighboring-group effect of the 2-acetamido-group, 1,2-oxazolines are generated and converted into 1-glycosyl thioesters through treatment with 1-thioacids. The unprotected anomeric glycosyl thiolates released in situ were conjugated to Michael acceptors, aliphatic halogenides, and aziridines to furnish versatile glycoconjugates. Conjugation of amino acids and proteins was accomplished using the thiol-ene reaction with terminal olefins. This method gives efficient access to anomeric glycosyl thiols and thiolates, which enables anomeric ligations of complex unprotected glycans in water.
authors.affiliation: Medicinal Chemistry, Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195, Berlin, Germany.|Institut für Biophysik, Universität Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Köhling
authors.affiliation: Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Exner
authors.affiliation: Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany.
authors.forename: Saba
authors.initials: S
authors.lastname: Nojoumi
authors.affiliation: Institut für Biophysik, Universität Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.affiliation: Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Strasse 10, 10623, Berlin, Germany.
authors.forename: Nediljko
authors.initials: N
authors.lastname: Budisa
authors.affiliation: Medicinal Chemistry, Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195, Berlin, Germany.|Institut für Biophysik, Universität Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany.
authors.forename: Jörg
authors.identifier: 0000-0001-6678-3165
authors.initials: J
authors.lastname: Rademann
keywords: bioorthogonal conjugation; carbohydrate chemistry; glycobiology; glycosyl thiols; oligosaccharides