Glycosidation of Thioglycosides in the Presence of Bromine: Mechanism, Reactivity, and Stereoselectivity

Elaborating on previous studies by Lemieux for highly reactive “armed” bromides, we discovered that β-bromide of the superdisarmed (2-<i>O</i>-benzyl-3,4,6-tri-<i>O</i>-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

Regenerative Glycosylation under Nucleophilic Catalysis

This article describes 3,3-difluoroxindole (HOFox)-mediated glycosylation. The uniqueness of this approach is that both the in situ synthesis of 3,3-difluoro-3<i>H</i>-indol-2-yl (OFox) glycosyl donors and activation thereof can be conducted in a regenerative fashion as is a typical reaction performed under nucleophilic catalysis. Only a catalytic amount of the OFox imidate donor and a Lewis acid activator are present in the reaction medium. The OFox imidate donor is constantly regenerated upon its consumption until glycosyl acceptor has reacted

HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery

The development of a useful methodology for simple, scalable, and transformative automation of oligosaccharide synthesis that easily interfaces with existing methods is reported. The automated synthesis can now be performed using accessible equipment where the reactants and reagents are delivered by the pump or the autosampler and the reactions can be monitored by the UV detector. The HPLC-based platform for automation is easy to setup and adapt to different systems and targets

<i>S</i>‑Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

This article describes the development of <i>S</i>-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

Regenerative Glycosylation

Previously, we communicated 3,3-difluoroxindole (HOFox)-mediated glycosylations wherein 3,3-difluoro-3<i>H</i>-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study to the synthesis of various glycosidic linkages using different sugar series. The main outcome of this study relates to enhanced yields and/or reduced reaction times of glycosylations. The effect of HOFox-mediated reactions is particularly pronounced in case of unreactive glycosyl donors and/or glycosyl acceptors. A multistep regenerative synthesis of oligosaccharides is also reported

How O-Substitution of Sialyl Donors Affects Their Stereoselectivity

The profound effect of substituents at C-5 of glycosyl sialosides on their stereoselectivity is well-known although the exact nature of this effect is somewhat less understood. Presented herein is a comparative study of a range of novel sialyl donors with various O-substituents. It is demonstrated that O-substituents at C-4 and C-7 may also have a significant effect on the reactivity of sialyl donors and on the stereoselectivity of chemical sialylation

Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects

A novel glycosyl donor that combines the concepts of both conformational and electronic superarming has been synthesized. The reactivity and selectivity of the donor have been tested in competition experiments

Surface-Tethered Iterative Carbohydrate Synthesis: A Spacer Study

Comparative study of Surface-Tethered Iterative Carbohydrate Synthesis (STICS) using HPLC-assisted experimental setup clearly demonstrates benefits of using longer spacer-anchoring systems. The use of mixed self-assembled monolayers helps provide the required space for glycosylation reaction around the immobilized glycosyl acceptor. Both extension of the spacer length and using mixed self-assembled monolayers help promote the reaction, and the beneficial effects may include moving the glycosyl acceptor further out into solution and providing additional conformational flexibility. It is possible that surface-immobilized glycosyl acceptors with a longer spacer (C8–O–C8)-lipoic acid have a higher tendency to mimic a solution-phase reaction environment than acceptors with shorter spacers

A Concise Synthesis of the Repeating Unit of Capsular Polysaccharide <i>Staphylococcus aureus</i> Type 8

The first synthesis of the repeating unit of <i>S. aureus</i> capsular polysaccharide type 8 is described. The repeating unit is an unusual trisaccharide sequence of three uncommon sugars, all connected via 1,2-<i>cis</i> linkages. The synthetic trisaccharide was equipped with capping methyl groups at the points of propagation of the polysaccharide sequence