Advances in the chemical synthesis of C-pyranosides/furanosides are summarized, covering the literature from 2000 to 2016. The majority of the methods take advantage of the construction of the glycosidic C—C bond. These C-glycosylation methods are categorized herein in terms of the glycosyl donor precursors, which are commonly used in O-glycoside synthesis and are easily accessible to nonspecialists. They include glycosyl halides, glycals, sugar acetates, sugar lactols, sugar lactones, 1,2-anhydro sugars, thioglycosides/sulfoxides/sulfones, selenoglycosides/telluroglycosides, methyl glycosides, and glycosyl imidates/phosphates. Mechanistically, C-glycosylation reactions can involve glycosyl electrophilic/cationic species, anionic species, radical species, or transition-metal complexes, which are discussed as subcategories under each type of sugar precursor. Moreover, intramolecular rearrangements, such as the Claisen rearrangement, Ramberg–Backlund rearrangement, and 1,2-Wittig rearrangement, which usuall...

Recent Advances in the Chemical Synthesis of C-Glycosides

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.

A critical review of the state-of-the-art evidence in support of the mechanisms of glycosylation reactions is provided. Factors affecting the stability of putative oxocarbenium ions as intermediates at the SN1 end of the mechanistic continuum are first surveyed before the evidence, spectroscopic and indirect, for the existence of such species on the time scale of glycosylation reactions is presented. Current models for diastereoselectivity in nucleophilic attack on oxocarbenium ions are then described. Evidence in support of the intermediacy of activated covalent glycosyl donors is reviewed, before the influences of the structure of the nucleophile, of the solvent, of temperature, and of donor–acceptor hydrogen bonding on the mechanism of glycosylation reactions are surveyed. Studies on the kinetics of glycosylation reactions and the use of kinetic isotope effects for the determination of transition-state structure are presented, before computational models are finally surveyed. The review concludes with ...

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The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1–SN2 Interface

Glycosyl ortho-alkynylben- zoates have emerged as a new genera- tion of donors for glycosidation under the catalysis of gold(I) complexes such as Ph3PAuOTf and Ph3PAuNTf2 (Tf = trifluoromethanesulfonate). A wide va- riety of these donors, including 2-deoxy sugar and sialyl donors, are easily pre- pared and shelf stable. The glycosidic coupling yields with alcohols are gener- ally excellent; even direct coupling with the poorly nucleophilic amides gives satisfactory yields. Moreover, ex- cellent a-selective glycosylation with a 2-deoxy sugar donor and b-selective sialylation have been realized. Applica- tion of the present glycosylation proto- col in the efficient synthesis of a cyclic triterpene tetrasaccharide have further demonstrated the versatility and effica- cy of this new method, in that a novel chemoselective glycosylation of the car- boxylic acid and a new one-pot sequen- tial glycosylation sequence have been implemented.

Gold(I)‐Catalyzed Glycosylation with Glycosyl ortho‐Alkynylbenzoates as Donors: General Scope and Application in the Synthesis of a Cyclic Triterpene Saponin

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

Recent advances in the synthesis of 2-deoxy-glycosides.

A series of investigations probing the mechanism of the 2,3-anhydrosugar migration−glycosylation reaction were performed using a thioglycoside with the d-lyxo stereochemistry as the substrate. Among the work reported are the results of quantum mechanical calculations, NMR studies, the measurement of α-deuterium kinetic isotope effects, and the synthesis of a series of substrate analogues. All studies point to a consistent finding: that the reaction proceeds through an oxocarbenium ion intermediate, not an episulfonium ion as previously suggested. It is proposed that the high stereoselectivity of the reaction arises from a preferred “inside attack” of the nucleophile onto the oxocarbenium ion intermediate.

2,3-Anhydrosugars in glycoside bond synthesis: mechanism of 2-deoxy-2-thioaryl glycoside formation.

In Vitro Reconstruction of the Chain Termination Reaction in Biosynthesis of the Escherichia coli O9a O-Polysaccharide THE CHAIN-LENGTH REGULATOR, WbdD, CATALYZES THE ADDITION OF METHYL PHOSPHATE TO THE NON-REDUCING TERMINUS OF THE GROWING GLYCAN

We describe here the first use of 2,3-anhydrosugars as glycosylating agents for the preparation of 2-deoxypyranosides. In particular, the methodology was used to assemble 2,6-dideoxysugar glycosides. Glycosylation of a panel of alcohols with one of two 6-deoxy-2,3-anhydrosugar thioglycosides (8 and 9) in the presence of a Lewis acid afforded 2,6-dideoxy-2-thiotolyl glycoside products in generally excellent yields with an exclusively syn relationship between the aglycon and the C-3 hydroxyl group. Removal of the 2-thiotolyl group can be achieved upon reaction with tri-n-butyltin hydride and AIBN to give the corresponding 2,6-dideoxy pyranosides. Once developed, the method was applied to the synthesis of oligosaccharide moieties in the natural products apoptolidin and olivomycin A.

Dianjie Hou

Papers

Recent advances in the synthesis of 2-deoxy-glycosides.

2,3-Anhydrosugars in glycoside bond synthesis: mechanism of 2-deoxy-2-thioaryl glycoside formation.

In Vitro Reconstruction of the Chain Termination Reaction in Biosynthesis of the Escherichia coli O9a O-Polysaccharide THE CHAIN-LENGTH REGULATOR, WbdD, CATALYZES THE ADDITION OF METHYL PHOSPHATE TO THE NON-REDUCING TERMINUS OF THE GROWING GLYCAN

2,3-Anhydrosugars in Glycoside Bond Synthesis. Application to 2,6-Dideoxypyranosides

Stereoselective synthesis of 2-deoxy-furanosides from 2,3-anhydro-furanosyl thioglycosides.