Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

Wouter A. Remmerswaal, Hidde Elferink, Kas J. Houthuijs, Thomas Hansen, Floor ter Braak, Giel Berden, Stefan van der Vorm, Jonathan Martens, Jos Oomens, Gijsbert A. van der Marel, Thomas J. Boltje, Jeroen D.C. Codée*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Minimal structural differences in the structure of glycosyl donors can have a tremendous impact on their reactivity and the stereochemical outcome of their glycosylation reactions. Here, we used a combination of systematic glycosylation reactions, the characterization of potential reactive intermediates, and in-depth computational studies to study the disparate behavior of glycosylation systems involving benzylidene glucosyl and mannosyl donors. While these systems have been studied extensively, no satisfactory explanations are available for the differences observed between the 3-O-benzyl/benzoyl mannose and glucose donor systems. The potential energy surfaces of the different reaction pathways available for these donors provide an explanation for the contrasting behavior of seemingly very similar systems. Evidence has been provided for the intermediacy of benzylidene mannosyl 1,3-dioxanium ions, while the formation of the analogous 1,3-glucosyl dioxanium ions is thwarted by a prohibitively strong flagpole interaction of the C-2-O-benzyl group with the C-5 proton in moving toward the transition state, in which the glucose ring adopts a B2,5-conformation. This study provides an explanation for the intermediacy of 1,3-dioxanium ions in the mannosyl system and an answer to why these do not form from analogous glucosyl donors.

Original languageEnglish
Pages (from-to)1618-1625
Number of pages8
JournalJournal of Organic Chemistry
Volume89
Issue number3
Early online date18 Jan 2024
DOIs
Publication statusPublished - 2 Feb 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.

Funding

Quantum chemical calculations were performed at the SURFsara HPC center in Amsterdam (2021/ENW/01070753 and 2023/ENW/01446401 awarded to J.D.C.C and 2021/ENW/055 awarded to J.O.). This research was supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO-VICIVI.C.182.020 and NWO-VIDIVI.C.182.020 to J.D.C.C. and VI.Vidi.192.070 to T.J.B.) and the European research Council (ERC-CoG-726072-“GLYCONTROL” to J.D.C.C.). We gratefully acknowledge the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) for the support of the FELIX Laboratory through the research program “National Roadmap Grootschalige Wetenschappelijke Infastructuur” 184.034.022.

FundersFunder number
European Research Council184.034.022, ERC-CoG-726072
Nederlandse Organisatie voor Wetenschappelijk OnderzoekVI.Vidi.192.070, NWO-VIDIVI.C.182.020

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