Stereoselectivity of Conformationally Restricted Glucosazide Donors

Abstract

Glycosylations of 4,6-tethered glucosazide donors with a panel of model acceptors revealed the effect of acceptor nucleophilicity on the stereoselectivity of these donors. The differences in reactivity among the donors were evaluated in competitive glycosylation reactions, and their relative reactivities were found to be reflected in the stereoselectivity in glycosylations with a set of fluorinated alcohols as well as carbohydrate acceptors. We found that the 2-azido-2-deoxy moiety is more β-directing than its C-2-O-benzyl counterpart, as a consequence of increased destabilization of anomeric charge development by the electron-withdrawing azide. Additional disarming groups further decreased the α-selectivity of the studied donors, whereas substitution of the 4,6-benzylidene acetal with a 4,6-di-tert-butyl silylidene led to a slight increase in α-selectivity. The C-2-dinitropyridone group was also explored as an alternative for the nonparticipating azide group, but this protecting group significantly increased β-selectivity. All studied donors exhibited the same acceptor-dependent selectivity trend, and good α-selectivity could be obtained with the weakest acceptors and most reactive donors.

Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity

“…This gives a simpler reaction mechanism manifold than an in situ activation approach, which makes it easier to analyze the effects of changing the reactivity of the building blocks used. For both donors, we previously established a strong relationship between acceptor reactivity and glycosylation stereoselectivity, and across the board, glycosylations of donor B provided more β‐product than the glycosylations of donor A ,. This effect was accounted for by the greater tendency of donor B to partake in S N 2‐type reactions as a result of the electron‐withdrawing effect of the C‐2 azide and the greater stability of the anomeric triflate that is formed as a reactive intermediate.…”

Reactivity–Stereoselectivity Mapping for the Assembly of Mycobacterium marinum Lipooligosaccharides

“…The signals of the anomeric H and C atoms appeared at δ 4.7 ppm and δ 90.4 ppm for 1 H and 13 C respectively, which is significantly upfield from signals corresponding to an anomeric triflate or oxosulfonium triflate species (generally found at 1 H: δ ~5-6.5 ppm and 13 C: δ ~105-110 ppm). [42,[44][45][46][47] Warming the sample did not lead to any degradation of the initially formed product, and therefore it could be isolated. NMR analysis ( 1 H, 13 Cyclization reactions on activated glycosyl donors have been reported before (for example from a C6-OBn to form a 1,6-anhydrosugar) [48] , but the rate with which the caryophyllose/yersiniose cyclization takes place is striking.…”

Carbohydrate‐Scaffolded Thymine Multimers: Scope and Limitations of the Allylation–Hydroboration Sequence

“…Whereas the hydroboration of 5 leads to more than 80 % of yield deficiency, the hydroboration of 22 on the other hand, can be considered a favourable step. Diverse hydroboration yields might also be attributed to conformational specifics associated with the sugar ring, which are often and unexpectedly guiding carbohydrate chemistry . In the future, we will consequently employ the more high‐yielding synthetic sequences when hydroxypropylated glycoside platforms are required.…”