Catalyst‐Controlled Glycosylation

Abstract

Whereas highly practical chemical methods for the synthesis of polypeptides and polynucleotides are well established and in common use, glycan synthesis remains a challenging endeavor largely reserved for specialists in sugar chemistry. Glycosylation reactions are fundamentally challenging relative to peptide and nucleotide couplings, which involve non‐stereogenic linkages that are not strongly affected by the identity of the specific reacting partners. Carbohydrate couplings engage highly variable, stereochemically complex, and densely functionalized reacting partners, while generating a new stereocenter in the glycosidic linkage. Glycosylation methods that can be applied easily and broadly would be greatly enabling to research concerning the role of sugars in biological chemistry and medicine. Recent developments in transition‐metal catalysis and organocatalysis have enabled selective glycosylation reactions with catalyst‐controlled stereo‐ and site selectivity, making headway toward the longstanding goal of achieving generality in chemical glycosylation. This chapter highlights seminal examples of catalyst control in glycosylation, focusing on cases wherein catalyst structure and electronics play a demonstrated role in the stereochemical outcome of a glycosylation reaction.

Synthesis of C-acyl furanosides via the cross-coupling of glycosyl esters with carboxylic acids

“…C -Acyl glycosides are versatile synthetic intermediates to natural products, nucleoside analogues, and pharmaceutical molecules ( Scheme 1A ). 1 Downstream derivatives of C -acyl glycosides, including C -alkyl glycosides, 2 diazo derivatives, 3 alcohols, 4 nucleoside analogues, 5 and cyclopentitols, 6 display significant potentials in drug discovery and utilities in chemical biology and biochemistry studies. A C -glycoside linkage confers in vivo stability towards hydrolysis and enzymatic degradation.…”

Stereospecific Furanosylations Catalyzed by Bis-thiourea Hydrogen-Bond Donors

“…Inspired by enzymatic glycosylations that proceed via stereospecific displacement of phosphate leaving groups, − our group recently discovered that bis-thiourea hydrogen-bond donors such as 4a (Figure ) catalyze the stereospecific addition of alcohol acceptors to pyranosyl phosphate donors (Figure B) . The catalysts are hypothesized to engage the anomeric phosphate leaving group through a network of hydrogen bonds, while activating the acceptor through a general base interaction with one of the amides on the catalyst.…”

Gold(III) Chloride─tert-Butyl Cyanide Catalyzed Glycosidations with O-Glycosyl Trihaloacetimidates

“…To further support our hypothesis, 13 C-NMR studies of the interaction between AuCl3 and tert-BuCN were carried out. After mixing of AuCl3 (1.0 equivalent) and tert-BuCN (1.0 equivalent), the CN-signal disappeared, thus indicating reversible complex formation of AuCl3 with tert-BuCN (Figure 1).…”

“…1 Hence, many efforts were devoted to this reaction. [2][3][4][5][6][7][8] Among the reported strategies, glycosidations with the help of a catalyst [9][10][11][12][13] are particularly attractive, also with regard to application prospects in industrial production. Inspired by nature, we developed recently an acid─base catalysis glycosidation pathway 10 : A catalyst, with (i) low affinity to the glycosyl donor leaving group, but with (ii) high affinity to the acceptor, binds the acceptor ROH to generate reversibly a RO−Cat−H adduct.…”