Characterization of glycosyl dioxolenium ions and their role in glycosylation reactions

• Published in: Nature communications Vol. 11; no. 1; p. 2664
• Main Authors: Hansen, Thomas, Elferink, Hidde, van Hengst, Jacob M A, Houthuijs, Kas J, Remmerswaal, Wouter A, Kromm, Alexandra, Berden, Giel, van der Vorm, Stefan, Rijs, Anouk M, Overkleeft, Hermen S, Filippov, Dmitri V, Rutjes, Floris P J T, van der Marel, Gijsbert A, Martens, Jonathan, Oomens, Jos, Codée, Jeroen D C, Boltje, Thomas J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 29.05.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Biological research; Carbohydrate Conformation; Chemical reactions; Computational Chemistry - methods; Dioxoles - chemistry; Galactose - chemistry; Glucose - chemistry; Glycoconjugates; Glycosylation; Infrared spectroscopy; Intermediates; Ions; Linkages; Mannose - chemistry; Oligosaccharides; Oligosaccharides - chemical synthesis; Selenium Compounds - chemistry; Spectrophotometry, Infrared; Spectroscopy; Spectrum analysis; Stereoselectivity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16362-x

Controlling the chemical glycosylation reaction remains the major challenge in the synthesis of oligosaccharides. Though 1,2-trans glycosidic linkages can be installed using neighboring group participation, the construction of 1,2-cis linkages is difficult and has no general solution. Long-range participation (LRP) by distal acyl groups may steer the stereoselectivity, but contradictory results have been reported on the role and strength of this stereoelectronic effect. It has been exceedingly difficult to study the bridging dioxolenium ion intermediates because of their high reactivity and fleeting nature. Here we report an integrated approach, using infrared ion spectroscopy, DFT computations, and a systematic series of glycosylation reactions to probe these ions in detail. Our study reveals how distal acyl groups can play a decisive role in shaping the stereochemical outcome of a glycosylation reaction, and opens new avenues to exploit these species in the assembly of oligosaccharides and glycoconjugates to fuel biological research.