Nucleophile-directed stereocontrol over glycosylations using geminal-difluorinated nucleophiles
Authors list
Ben Schumann Sharavathi G Parameswarappa Marilda P Lisboa Naresh Kottari Fabio Guidetti Claney L Pereira Peter H SeebergerAbstract
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 alpha-terminating synthetic glycans for the formation of glycoconjugates.
Journal details
Journal Angew Chem Int Ed Engl
Volume 55
Issue number 46
Pages 14431-14434
Available online
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Publisher website (DOI) 10.1002/anie.201606774
Europe PubMed Central 27735117
Pubmed 27735117
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