Direct and Regioselective Di‐α‐fucosylation on the Secondary Rim of β‐Cyclodextrin

• Published in: Chemistry : a European journal Vol. 25; no. 27; pp. 6722 - 6727
• Main Authors: Verkhnyatskaya, Stella A., de Vries, Alex H., Douma‐de Vries, Elmatine, Sneep, Renze J. L., Walvoort, Marthe T. C.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.05.2019; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: beta-cyclodextrin; Chemistry; Chemistry, Multidisciplinary; Cyclodextrin; Cyclodextrins; Fucose; fucosylation; Glycosylation; mass fragmentation; Molecular dynamics; molecular dynamics simulations; NMR; Nuclear magnetic resonance; Physical Sciences; regioselectivity; Science & Technology; molecular dynamics simulations; regioselectivity; MOLECULAR-DYNAMICS; DESIGN; RECOGNITION; CYCLOMALTOHEPTAOSE; DE-O-BENZYLATION; POWERFUL; FUCOSE; MASS-SPECTROMETRY; mass fragmentation; HYDRIDE; fucosylation; BIOLOGICAL EVALUATION; beta-cyclodextrin
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201806090

A straightforward glycosylation method is described to regio‐ and stereoselectively introduce two α‐l‐fucose moieties directly to the secondary rim of β‐cyclodextrin. Using NMR and MS fragmentation studies, the nonasaccharide structure was determined, which was also visualized using molecular dynamics simulations. The reported glycosylation method proved to be robust on gram‐scale, and may be generally applied to directly glycosylate β‐cyclodextrins to make well‐defined multivalent glycoclusters. A robust method to decorate β‐cyclodextrin with two fucoses through direct glycosylation is developed. Using kinetic reaction conditions, the regioselectivity was steered towards the 3A,3D‐fucosylated nonasaccharide. The structure was elucidated using a combination of HPLC, NMR and MS fragmentation, and visualized using MD simulations.