Recent developments in stereoselective 1,2-cis glycosylation that have emerged during the past decade are surveyed herein. For detailed coverage of the previous achievements in the field the reader is referred to our earlier reviews: A. V. Demchenko, Curr. Org. Chem., 2003, 7, 35–79 and Synlett, 2003, 1225–1240.

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Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry

Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

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Methods for 2-Deoxyglycoside Synthesis.

Catalytic glycosylation has been a central reaction in carbohydrate chemistry since its introduction by Fischer 125 years ago, but it is only in the past three to four decades that catalytic methods for synthesizing oligosaccharides have appeared. Despite the development of numerous elegant and ingenious catalytic glycosylation methods, only a few are in general use. This review covers all methods of catalytic glycosylation with the focus on the development and application in oligosaccharide synthesis and provide an overview of the scope and limitations of these. The review also includes relevant mechanistic studies of catalytic glycosylations. The future of catalytic glycosylation chemistry is discussed, including specific, upcoming methods and possible directions for the field of research in general.

Catalytic Glycosylations in Oligosaccharide Synthesis

The efficient and stereoselective construction of glycosidic linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as β-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce β-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an α-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an SN2-pathway.

A reagent-controlled SN2-glycosylation for the direct synthesis of β-linked 2-deoxy-sugars.

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%207/Doplnkove%20studijne%20materialy/Reactions%20of%20sugars/A%20propos%20of%20glycosyl%20cations%20and%20the%20mechanism%20of%20chemical%20glycosylation.pdf

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art.

An approach for direct synthesis of biologically significant 2-deoxy-β-glycosides has been developed via O-alkylation of a variety of 2-deoxy-sugar-derived anomeric alkoxides using challenging secondary triflates as electrophiles. It was found a free hydroxyl group at C3 of the 2-deoxy-sugar-derived lactols is required in order to achieve synthetically efficient yields. This method has also been applied to the convergent synthesis of a 2-deoxy-β-tetrasaccharide.

Direct synthesis of 2-deoxy-β-glycosides via anomeric O-alkylation with secondary electrophiles.

A mild and atom-economic gold(I)-catalyzed glycosylation for stereoselective synthesis of 2-deoxy α-glycosides using bench-stable 2-deoxy S-But-3-ynyl thioglycoside donors has been described. Under optimal conditions, 2-deoxy and 2,6-dideoxy thioglycoside donors were able to react with a variety of primary, secondary, and tertiary alcohol acceptors to afford α-selective glycosides in good to excellent yields.

Gold-Catalyzed Synthesis of 2-Deoxy Glycosides Using S-But-3-ynyl Thioglycoside Donors

sugars play a critical role in the biological activity of these compounds as well as their stability and solubility. [10] As a result, considerable effort has been devoted to the stereoselective synthesis of 2-deoxyglycosides and the study of their structure–activity relationships. [11] Despite the significance of 2-deoxysugar subunits, the glycosidic linkage of 2deoxyglycosides has been found to be susceptible to hydrolysis in acid media or by glycosyl hydrolases. This reactivity has made it difficult to pinpoint the biological role of these 2deoxysugars, has resulted in toxicity [12] and reduced activity [13] of the parent molecules, and has limited their use as clinical agents. Thioglycosides (S-linked glycosides), [14] in which the glycosidic oxygen atom is replaced with a sulfur atom, are resistant towards enzymatic cleavage as well as chemical degradation. Furthermore, thioglycosides maintain the biological activity of their parent O-linked glycosides and are tolerated by most biological systems. Therefore, they are an important tool for structural biology [15] and attractive therapeutic agents. Because of these characteristics, the preparation of S-linked 2-deoxysugars for comparison of their physical, chemical, and biological properties with those of their natural O-linked counterparts is beneficial. Although a number of protocols are available for the synthesis of thioglycosides, [14, 16] there is no efficient method for the

Umpolung reactivity in the stereoselective synthesis of S-linked 2-deoxyglycosides.

A mild and atom-economic rhenium(V)-catalyzed stereoselective synthesis of β-D-digitoxosides from 6-deoxy-D-allals has been described This β-selective glycosylation was achieved probably because of the formation of corresponding α-digitoxosides disfavored by 1,3-diaxial interaction In addition, this method has been successfully applied to the synthesis of digitoxin trisaccharide glycal for the direct synthesis of digitoxin and C1'-epi-digitoxin

Kedar N. Baryal

Papers

Direct synthesis of 2-deoxy-β-glycosides via anomeric O-alkylation with secondary electrophiles.

Gold-Catalyzed Synthesis of 2-Deoxy Glycosides Using S-But-3-ynyl Thioglycoside Donors

Umpolung reactivity in the stereoselective synthesis of S-linked 2-deoxyglycosides.

Catalytic stereoselective synthesis of β-digitoxosides: direct synthesis of digitoxin and C1'-epi-digitoxin.

Stereoselective Synthesis of S-Linked Hexasaccharide of Landomycin A via Umpolung S-Glycosylation.