title: Nucleophile-Directed Stereocontrol Over Glycosylations Using Geminal-Difluorinated Nucleophiles.
abstract: The glycosylation reaction is the key transformation in oligosaccharide synthesis, but it is still difficult to control in many cases. Stereocontrol during cis-glycosidic linkage formation relies almost exclusively on tuning the glycosylating agent or the reaction conditions. Herein, we use nucleophile-directed stereocontrol to manipulate the stereoselectivity of glycosylation reactions. Placing two fluorine atoms in close proximity to the hydroxy group of an aliphatic amino alcohol lowers the oxygen nucleophilicity and reverses the stereoselectivity of glycosylations to preferentially form the desired cis-glycosides with a broad set of substrates. This concept was applied to the design of a cis-selective linker for automated glycan assembly. Fluorination of an amino alcohol linker does not impair glycan immobilization and lectin binding as illustrated by glycan microarray experiments. These fluorinated linkers enable the facile generation of α-terminating synthetic glycans for the formation of glycoconjugates.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany.
authors.forename: Benjamin
authors.identifier: 0000-0001-5504-0147
authors.initials: B
authors.lastname: Schumann
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany.
authors.forename: Sharavathi G
authors.identifier: 0000-0003-2785-6063
authors.initials: SG
authors.lastname: Parameswarappa
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany.
authors.forename: Marilda P
authors.initials: MP
authors.lastname: Lisboa
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kottari
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany.
authors.forename: Fabio
authors.initials: F
authors.lastname: Guidetti
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany. claney.pereira@vaxxilon.com.
authors.forename: Claney L
authors.identifier: 0000-0003-1972-7907
authors.initials: CL
authors.lastname: Pereira
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424, Potsdam, Germany. peter.seeberger@mpikg.mpg.de.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany. peter.seeberger@mpikg.mpg.de.
authors.forename: Peter H
authors.identifier: 0000-0003-3394-8466
authors.initials: PH
authors.lastname: Seeberger
keywords: diastereoselectivity; fluorine; glycosylation; microarrays; nucleophilicity