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Handbook of chemical glycosylation : advances in stereoselectivity and therapeutic relevance

TL;DR: The GLYCOSIDIC BOND FORMATION (GLBP) as discussed by the authors is a non-profit organization dedicated to the support of the GLYCLOSIDE SYNTHESIS from anomeric transglycosylation.
Abstract: GENERAL ASPECTS OF THE GLYCOSIDIC BOND FORMATION GLYCOSIDE SYNTHESIS FROM ANOMERIC HALIDES Glycosyl Fluorides Glycosyl Chlorides, Bromides, and Iodides GLYCOSIDE SYNTHESIS FROM 1-OXYGEN-SUBSTITUTED GLYCOSYL DONORS Hemiacetals and O-Acyl/Carbonyl Derivatives Glycosyl Imidates Anomeric Transglycosylation Phosphites, Phosphates, and Other O--P Derivatives GLYCOSIDE SYNTHESIS FROM 1-SULFUR/SELENIUM-SUBSTITUTED DERIVATIVES Thioalkyl and Thioaryl Glycosides Sulfoxides, Sulfimides, and Sulfones Xanthates, Thioimidates, and Other Thio Derivatives Selenoglycosides OTHER METHODS FOR GLYCOSIDE SYNTHESIS Orthoesters and Related Derivatives Dehydro and Anhydro Derivatives Miscellaneous Glycosyl Donors Indirect and Special Methods
Citations
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Journal ArticleDOI
TL;DR: The realization that in the glucopyranose series the 4,6-O-benzylidene acetal is alpha- rather than beta-directing led to further investigations of substituent effects on the stereoselectivity of these glycosylation reactions, culminating in their explanation in terms of the covalent alpha-glycosyl triflates acting as a reservoir for a series of transient contact and solvent-separated ion pairs.
Abstract: Glycosylation is arguably the most important reaction in the field of glycochemistry, yet it involves one of the most empirically interpreted mechanisms in the science of organic chemistry. The β-mannopyranosides, long considered one of the more difficult classes of glycosidic bond to prepare, were no exception to this rule. A number of logical but circuitous routes for their preparation were described in the literature, but they were accompanied by an even greater number of mostly ineffective recipes with which to access them directly. This situation changed in 1996 with the discovery of the 4,6-O-benzylidene acetal as a control element permitting direct entry into the β-mannopyranosides, typically with high yield and selectivity. The unexpected nature of this phenomenon demanded study of the mechanism, leading first to the demonstration of the α-mannopyranosyl triflates as reaction intermediates and then to the development of α-deuterium kinetic isotope effect methods to probe their transformation into ...

391 citations

PatentDOI
TL;DR: In this article, a method for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as "tags" into cellular glycoconjugates is presented.
Abstract: The present disclosure relates to a method for metabolic oligosaccharide engineering that incorporates derivatized alkyne-bearing sugar analogs as “tags” into cellular glycoconjugates. The disclosed method incorporates alkynyl derivatized Fuc and alkynyl derivatized ManNAc sugars into a cellular glycoconjugate. A chemical probe comprising an azide group and a visual probe or a fluorogenic probe is used to label the alkyne-derivatized sugar-tagged glycoconjugate. In one aspect, the chemical probe binds covalently to the alkynyl group by Cu(I)-catalyzed [3+2] azide-alkyne cycloaddition and is visualized at the cell surface, intracellularly, or in a cellular extract. The labeled glycoconjugate is capable of detection by flow cytometry, SDS-PAGE, Western blot, ELISA or confocal microscopy, and mass spectrometry.

294 citations

Journal ArticleDOI
13 Jan 2017-Science
TL;DR: The discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides is reported, and the utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis- 1,2, and 2-deoxy-β-glycosides.
Abstract: Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.

168 citations


Cites background from "Handbook of chemical glycosylation ..."

  • ...The stereochemical outcome of glycosylation reactions is influenced to varying degrees by the steric and electronic properties of the coupling partners, and the problem of stereoselective glycosylation has historically been addressed by tailoring the protecting groups and couplingmethod to achieve high diastereoselectivity (8, 9)....

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Journal ArticleDOI
TL;DR: Primary 13C kinetic isotope effects have been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method, revealing both associative and dissociative mechanisms at the extremes of a continuum that depends on the relative stereochemistry of the substrate and the anomeric configuration of the product.
Abstract: Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions, resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem, primary (13)C kinetic isotope effects have now been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental and computed values are indicative of associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides, the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of analogous experiments to other glycosylation systems should shed further light on their mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity.

155 citations

Book ChapterDOI
TL;DR: This chapter classifies and discusses significant recent improvements that have emerged to address the drawbacks of the traditional approach to chemical synthesis of complex oligosaccharide assembly.
Abstract: Although glycoscientists have learned over the years how to isolate certain classes of naturally occurring complex carbohydrates, the availability of pure natural isolates, remains inadequate to address the ongoing challenges. As a result, glycoscientists have turned to chemical synthesis for access to complex oligosaccharides and glycoconjugates. Efficient chemical synthesis of complex carbohydrates can yield significant quantities of the pure natural structures as well as unnatural mimetics that are often of interest. Traditional oligosaccharide synthesis, however, often requires extensive protecting‐group manipulations between each glycosylation step. Such additional manipulations increase the number of total synthetic steps and inevitably decrease the efficiency, as reflected in a dramatic drop in yield. This chapter classifies and discusses significant recent improvements that have emerged to address the drawbacks of the traditional approach. Expeditious new strategies effectively shorten the task of oligosaccharide assembly by minimizing the need for protecting‐group manipulations between glycosylation steps, or even purification of the intermediates. The excellent innovations surveyed here have already facilitated synthesis of complex oligosaccharides and glycoconjugates, and some representative examples are discussed herein.

116 citations