S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

Abstract

This article describes the development of S-benzimidazolyl (SBiz) imidates as versatile building blocks for oligosaccharide synthesis. The SBiz imidates have been originally developed as a new platform for active-latent glycosylations. This article expands upon the utility of these compounds. The application to practically all common concepts for the expeditious oligosaccharide synthesis including selective, chemoselective, and orthogonal strategies is demonstrated. The strategy development was made possible thanks to our enhanced understanding of the reaction mechanism and the modes by which SBiz imidates interact with various promoters of glycosylation.

Extending the S-benzimidazolyl (SBiz) platform: N-alkylated SBiz glycosyl donors with the universal activation profile

“…The outcome of the latter reaction was deemed similar to that of MeI-mediated activation of SBiz-H donor 1 . The activation mode via the anomeric sulfur was ultimately determined by isolation and characterization of the departed aglycone 7 [ 6 ].…”

“…On the one hand, by careful selection of reaction conditions we determined that KOH in THF offers a direct and high-yielding means to methylate the N-atom in compound 1 [ 6 ]. On the other hand, we also theorized that advantages of totally different approach involving methylation of 2-mercaptobenzoxazole prior to introducing it to the anomeric position would be two-fold.…”

“…The residue was purified by column chromatography on silica gel (ethyl acetate-hexane gradient elution) to afford the title compound (1.25 g, 83 % yield) as a white amorphous solid. Analytical data for 3 was the same as previously reported [ 6 ].…”

“…Conversely, a more recent study showed that the N -anisoylated SBiz (SBiz-An) leaving group is activated with dimethyl(thiomethyl)sulfonium triflate (DMTST) [ 5 ], but not with methyl iodide. This cooperative finding allowed us to create a new SBiz-based orthogonal approach to expeditious oligosaccharide synthesis [ 6 ]. While conducting a mechanistic study to understand the driving forces for this differential reactivity, we obtained N -methylated SBiz (SBiz-Me) derivatives.…”

Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges

“…A number of complementary combinations of orthogonal leaving groups and conceptual modifications have been implemented. 385,387,389–399…”