Stereoselective synthesis of 2-C-branched (acetylmethyl) oligosaccharides and glycoconjugates: Lewis acid-catalyzed glycosylation from 1,2-cyclopropaneacetylated sugars

摘要

1,2-Cyclopropaneacetylated sugars as glycosyl donors reacted with a series of glycosyl acceptors (monosaccharides, amino acids, and other alcohols) in the presence of Lewis acid to produce oligosaccharides and glycoconjugates containing 2-C-acetylmethylsugars. Galactosyl donor gave good to excellent α-selectivities with TMSOTf as a catalyst, whereas galactosyl donor offered moderate to good β-selectivities when BF_3·Et _2O was used as a catalyst. However, glucosyl donors produced β-exclusive selectivity under both conditions. The stereoselectivities of glycosylation depend on the reactivity of donor sugars and Lewis acid catalyst, which effectively dictated the glycosylation pathways. The evidence suggests that galactosyl donors (e.g., 7) can undergo S_N1 pathway with a strong Lewis acid (TMSOTf) and S_N2 pathway under BF _3·Et_2O, whereas the glucosyl donors (e.g., 8 and 10) followed S_N2 pathway. The stereoselectivity was also consequential to the formation of a C2′-acetal intermediate formed via the 2-C-acetylmethyl group and the anomeric carbonium intermediate in glycosylation.