Controlling the stereoselectivity of glycosylation via solvent effects

Abstract

This review covers a special topic in carbohydrate chemistry — solvent effects on the stereoselectivity of glycosylation reactions. Obtaining highly stereoselective glycosidic linkages is one of the most challenging tasks in organic synthesis, as it is affected by various controlling factors. One of the least understood factors is the effect of solvents. We have described the known solvent effects while providing both general rules and specific examples. We hope this review will not only help fellow researchers understand the known aspects of solvent effects and use that in their experiments, but moreover, we expect that more studies on this topic will be started and continued to expand our understanding of the mechanistic aspects of solvent effects in glycosylation reactions.

Ultrasensitive small molecule fluorogenic probe for human heparanase

“…The unexpected intermolecular aglycone transfer [31][32][33] was the predominant mainly due to the low reactivity of C4-hydroxyl group. Switching the solvent to toluene increased the formation of desired disaccharide, and further screening of the solvents achieved disaccharide 7 in 79% yield with a complete 1,2-cis-αselectivity, when the reaction was carried out in a 2/1 mixture of toluene and 1,4-dioxane 34 . Transformation of 7 into the corresponding brominated product 8 and further coupling with the fluorophore afforded the expected product in satisfying yield (55%) using silver oxide (Ag2O) as activating agent in acetonitrile.…”

Stereocontrolled Synthesis of α-Xylofuranosides Using a Conformationally Restricted Donor

“…These results are consistent with previous work indicating that that ethereal solvents tend to increase α-stereoselectivity in glycosylations. 24 It should be noted, however, that this effect in furanosides has not been widely studied.…”

Predicting glycosylation stereoselectivity using machine learning

“…Finally, the stereoselectivities of glucose and galactose -imidate electrophiles with isopropanol were predicted for two new solvents (Figure 6j/k). The strong influence of solvent 48,51 on the stereoselectivity of glycosylations is nicely captured by the descriptors chosen, and the model is accurate across a wide temperature range for both α,α,αtrifluorotoluene (RMSE: 6.2) and 1,4-dioxane (RMSE: 4.5). Figure 6.…”