It is reported that S-glycosyl O-methyl phenylcarbamothioates (SNea carbamothioates) have a fully orthogonal character in comparison to S-benzoxazolyl (SBox) glycosides. This complete orthogonality was revealed by performing competitive glycosylation experiments in the presence of various promoters. The results obtained indicate that SNea carbamothioates have a very similar reactivity profile to that of glycosyl thiocyanates, yet are significantly more stable and tolerate selected protecting group manipulations. These features make the SNea carbamothioates new promising building blocks for further utilization in oligosaccharide synthesis.

Elaborating on previous studies by Lemieux for highly reactive "armed" bromides, we discovered that β-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.

A new method for intramolecular oligosaccharide synthesis that is conceptually related to the general molecular clamp approach is introduced. Exceptional α-selectivity has been achieved in a majority of applications. Unlike other related concepts, this approach is based on the bisphenol A template, which allows one to connect multiple building blocks to perform templated oligosaccharide synthesis with complete stereoselectivity. This principle was demonstrated by the synthesis of an α,α-linked trisaccharide.

Thorough mechanistic studies of the alkylation pathway for the activation of glycosyl thioimidates have led to the development of the “thioimidate-only orthogonal strategy”. Discrimination amongst S-thiazolinyl (STaz) and S-benzoxazolyl (SBox) anomeric leaving group was achieved by fine-tuning of the activation conditions. Preferential glycosidation of a certain thioimidate is not simply determined by the strength of activating reagents; instead, the type of activation – direct vs. indirect – comes to the fore and plays the key role.

We have identified silver tetrafluoroborate (AgBF 4 ) as an excellent promoter for the activation of various glycosyl donors including glycosyl halides, trichloroacetimidates, thioimidates, etc. Easy handling and no requirement for azeotropic dehydration prior to application makes AgBF 4 especially beneficial in comparison to the commonly used AgOTf. Selective activation of glycosyl halides or thioimidates over thioglycosides or n-pentenyl glycosides, including simple sequential one-pot syntheses, has been also demonstrated. Versatility of glycosyl thioimidates was further explored by converting these intermediates into a variety of other classes of glycosyl donors.With increasing demand for the synthesis of biologically important and therapeutically active oligosaccharides and glycoconjugates, efforts to expand the arsenal of glycosylation methods and techniques have emerged. In spite of significant recent advances in the areas of stereoselective glycosylation 1,2 and expeditious oligosaccharide synthesis, 3,4 the construction of complex oligosaccharides with high efficiency and complete stereoselectivity remains a difficult task.As a part of a program to develop new methods and strategies for glycochemistry, we became interested in glycosyl thioimidates, a class of glycosyl donors with the generic leaving group SCR 1 =NR 2 . 5,6 We have already reported the synthesis of S-benzoxazolyl (SBox) 7,8 and Sthiazolinyl (STaz) 9,10 glycosides and evaluated their properties in stereoselective glycosylations and expeditious oligosaccharide syntheses. Metal salt-based promoters were shown to provide efficient activation of the thioimidoyl moiety for glycosylation. 8,11 Amongst a variety of metal salts investigated, arguably, silver trifluoromethanesulfonate (AgOTf) was one of the best choices for the activation of the SBox and STaz moieties for a variety of synthetic applications.Beyond the scope of our own research program, AgOTf has been commonly employed as an activator for many other classes of glycosyl donors including glycosyl bromides, 12-14 chlorides, 15 trichloroacetimidates, 16 and seleno glycosides. 17 In spite of wide applicability and high versatility of AgOTf, there are some significant drawbacks that limit the usage of this promoter in synthesis. In a majority of applications, AgOTf requires fresh activation by repetitive co-evaporation with toluene followed by extended drying under vacuum directly prior to use. In addition, we noticed that the quality of commercial reagent may significantly vary depending on the supplier and the batch. It should be noted that the use of AgOTf as an *Corresponding

Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby increasing the total number of synthetic steps while decreasing the efficiency of the synthesis. In contrast, expeditious strategies allow for the rapid chemical synthesis of complex carbohydrates by minimizing extraneous chemical manipulations. Oligosaccharide synthesis by selective activation of one leaving group over another is one such expeditious strategy. Herein, the significant improvements that have recently emerged in the area of the selective activation are discussed. The development of orthogonal strategy further expands the scope of the selective activation methodology. Surveyed in this article, are representative examples wherein these excellent innovations have been applied to the synthesis of various oligosaccharide sequences.

Discrimination amongst S-thiazolinyl (STaz), S-benzoxazolyl (SBox), and S-ethyl anomeric leaving group was achieved by fine-tuning of the activation conditions. Preferential glycosidation of a certain leaving group is neither determined by the strength of activating reagents nor the stability of the leaving group itself; instead, the type of activation comes to the fore and plays the key role. The activation conditions established herein were applied to a sequential five-step synthesis of a hexasaccharide using six monosaccharide building blocks equipped with six different leaving groups.

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