Preactivation: An Alternative Strategy in Stereoselective Glycosylation and Oligosaccharide Synthesis

Abstract

The multifaceted biological importance of carbohydrates has made them very popular targets in modern synthetic chemistry. Great progress has been made in stereoselective glycosylation methods and the construction of complex oligosaccharides. This Focus Review highlights the versatile applications of preactivation strategies in stereoselective glycosylation and oligosaccharide synthesis. Recent advances in synthetic methods, such as 4,6-O-benzylidene-acetal-directed b-mannosylation, the 1,2-cis-glycosylation mediated by a chiral auxiliary, the use of an oxazolidinone or carbonate protecting group, and glycosylation with participating additives, are described. Various examples of sequential glycosylation based on preactivation protocols for efficient oligosaccharide assembly are also summarized. Scheme 4. Mechanism for the 4,6-O-benzylidene-directed formation of a-and b-gluco-and mannopyranosides. CIP = contact ion pairs; SSIP = solvent-separated ion pairs Scheme 5. Fluorinated, deoxy, and deoxyfluoro glycosyl donors.

Reagent Controlled Stereoselective Synthesis of α-Glucans

“…These nucleophilic additives or reactivity modulators react with the activated donor to form a new covalent species (see Figure 1 ). 6 Various additives have been probed over the years, including sulfides, 7 sulfoxides/sulfinamides, 8 phosphine oxides, 9 amides and formamides 10 and iodide based reagents 11 and stereoselective 1,2- cis -glycosylation procedures have been reported based on their use. The most often invoked mechanistic rationale to account for the observed stereoselectivity involves the generation of a stable α-covalent species (often identified and characterized by NMR spectroscopy), that is in equilibrium with its less stable and more reactive β-counterpart (often not detected by NMR), following an in situ anomerisation kinetic scenario as first introduced by Lemieux and co-workers.…”

Additive-controlled stereoselective glycosylations of 2,3-oxazolidinone protected glucosamine or galactosamine thioglycoside donors with phenols based on preactivation protocol

“…Given the time window between the activation of donor and the addition of acceptor, this activated intermediate can be affected by adding other molecules, which can in turn affect the overall stereooutcomes of glycosylation reactions. 10 In 2004, Boons and co-workers reported that the a-selectivity of 2-azido-2-deoxy glycosyl donors could be greatly enhanced by the addition of PhSEt. 11 In 2006, Crich and co-workers reported that the additional diphenyl sulfoxide could stabilize the activated sialyl intermediate.…”

Assembly of a Complex Branched Oligosaccharide by Combining Fluorous‐Supported Synthesis and Stereoselective Glycosylations using Anomeric Sulfonium Ions

“…[5] For example, several synthetic strategies make it possible to assembly complex oligosaccharides from carefully selected monosaccharide building blocks using a minimal number of chemical steps. [6] Among these strategies, one-pot multi-step glycosylations, in which several glycosyl donors are sequentially reacted in the same flask, are particularly attractive and can furnish target oligosaccharides without the need for protecting group manipulations and isolation and purification of synthetic intermediates. [6c] Within the past few years, automated solid-phase oligosaccharide synthesis has also substantially advanced.…”

“…[6] Among these strategies, one-pot multi-step glycosylations, in which several glycosyl donors are sequentially reacted in the same flask, are particularly attractive and can furnish target oligosaccharides without the need for protecting group manipulations and isolation and purification of synthetic intermediates. [6c] Within the past few years, automated solid-phase oligosaccharide synthesis has also substantially advanced. [7] A host of glycosylating agents, new linker systems, different solid supports and a variety of protecting groups have been carefully evaluated and these efforts have resulted in the first commercially available glycan synthesizer.…”

“…[10] This limited application is most likely due to the difficulties of controlling anomeric selectivities in glycosylations and challenges to install branching points in high yield. [5a, 6a, 11] In this respect, many complex oligosaccharides are branched and due to steric crowding, the corresponding glycosylations are often low yielding. Furthermore, 1,2- trans -glycosides, such as β-glucosides and β-galactosides, can reliably be introduced by neighboring group participation of an ester-protecting group at C-2 of a glycosyl donor (Scheme 1A).…”