posted on 2024-01-18, 11:06authored byWouter
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
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.