Site-selective, stereocontrolled glycosylation of minimally protected sugars

Abstract

The identi cation of general and e cient methods for the construction of oligosaccharides stands as one of the great challenges for the eld of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly signi cant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical ine ciencies arise directly from the application of such approaches. We describe here a new strategy for small-moleculecatalyst-controlled, highly stereo-and site-selective glycosylations of unprotected or minimally protected mono-and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo-and siteselective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site selectivity arises from stabilizing C-H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing noncovalent interactions, a potentially general strategy for selective functionalization of carbohydrates.

Efficient one-pot synthesis of the unexpected fused multicyclic iminosugars by an aza-Diels–Alder mechanism

“…In general, directly obtaining deprotected saccharides has been difficult in multistep synthetic saccharide research because of the installation and removal of specific protective groups. 15 Our protocol provides quick access to complex iminosugars possibly through an aza-Diels–Alder mechanism.…”

A synergistic Rh(I)/organoboron-catalysed site-selective carbohydrate functionalization that involves multiple stereocontrol

“…An unresolved gap in this field pertains to the majority of currently developed chiral catalytic systems for this purpose being still limited to chiral copper complexes and organocatalysis (Fig. 1a) [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] , despite the overwhelming number of examples of asymmetric transition-metal complexes available for enantioselective catalysis. This severely limits selective bond-forming opportunities for carbohydrate functionalizations.…”

Site-Selective Modification of (Oligo)Saccharides

“…For example, the method of Fairbanks can only be applied using GlcNAc donors and the method of Miller and Schepartz only works for sucrose acceptors. However, lessons learned from the partly protected monosaccharides, such as organocatalysts like in a recent contribution from Wendlandt and Jacobsen et al, 57 that allow discriminating between the secondary hydroxy groups in the acceptor can eventually be translated to the fully unprotected carbohydrates. 58 …”