Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors

• Published in: Journal of organic chemistry 2019-05, Vol.84 (10), p.6405-6431
• Main Authors: Kurfiřt, Martin, Červenková Št’astná, Lucie, Dračínský, Martin, Müllerová, Monika, Hamala, Vojtěch, Cuřínová, Petra, Karban, Jindřich
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00705

Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4-fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the Tf2O/Ph2SO promoter system. Low-temperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions. This study demonstrates how the stereoselectivity depends on acceptor reactivity and glycosyl donor configuration. Reactive acceptors favor formation of 1,2-trans-β-glycosides with both d-gluco and d-galacto donors, whereas poorly reactive acceptors favor formation of 1,2-cis-α-glycosides with d-galacto donors but are unselective with d-gluco donors.