Site-Selective Functionalization of Hydroxyl Groups in Carbohydrate Derivatives

Abstract

Methods for site-selective transformations of hydroxyl groups in carbohydrate derivatives are reviewed. The construction of oligosaccharides of defined connectivity hinges on such transformations, which are also needed for the preparation of modified or non-natural sugar derivatives, the installation of naturally occurring postglycosylation modifications, the selective labeling or conjugation of carbohydrate derivatives, and the preparation of therapeutic agents or research tools for glycobiology. The review begins with a discussion of intrinsic factors and processes that can influence selectivity in reactions of unprotected or partially protected carbohydrate derivatives, followed by a description of transformations that engage two OH groups in cyclic adducts (acetals, ketals, boronic esters, and related species). An overview of the various classes of site-selective transformations of OH groups in sugars is then provided: the reactions discussed include esterification, thiocarbonylation, alkylation, glycosylation, arylation, silylation, phosphorylation, sulfonylation, sulfation, and oxidation. Emphasis is placed on recently developed methods that employ reagent or catalyst control to achieve otherwise challenging transformations or site-selectivities.

DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

“…The preparation of high value-added carbohydrates and building blocks for oligosaccharide synthesis still remains the most important scientific problem in carbohydrate chemistry. [1][2][3][4][5][6][7][8][9][10][11] Regioselective acylation is of great importance in the synthesis of valuable oligosaccharide structural units because it facilitates the protection and deprotection of hydroxyl groups and the synthesis of target building blocks. [12][13][14][15][16][17][18] Recently, many methods have been developed to make regioselective acylations highly efficient, green, and even controllable, and some metal catalysts and organic small molecules have been used for the regioselective acylation of carbohydrates and diols; for example, tin(IV), [19][20][21] boron(IV), [22] copper(II), [23][24][25] silver(I), [26] and iron catalysts have been recently reported.…”

Regio‐ and stereoselective glycosylation of 2‐(o‐dihydroxyborylbenzyl) thioglucoside and unprotected methyl glycosides

“…The traditional way to achieve the desired regioselectivity is by protecting all the hydroxyl groups not involving in glycosylation in the glycosyl acceptor prior to glycosylation. The tedious protecting group manipulation involved in this approach was not desirable and numerous efforts have been devoted to directly use fully unprotected or partially protected substrate for glycosylation . The insolubility of the highly polar unprotected sugars in organic solvents, which are the usual glycosylation media, posed an additional challenge for their direct glycosylation.…”

“…The tedious protecting group manipulation involved in this approach was not desirable and numerous efforts have been devoted to directly use fully unprotected or partially protected substrate for glycosylation. [1,2] The insolubility of the highly polar unprotected sugars in organic solvents, which are the usual glycosylation media, posed an additional challenge for their direct glycosylation. One way to tackle these problems in the literature was to use arylboronic acid, which is known to form cyclic boronic ester with 1,3-diol or cis-1,2-diol on the unprotected sugar, [3][4][5][6][7] to provide transient protection.…”

Glycosylation on Unprotected or Partially Protected Acceptors

“…During the last 30 years, numerous procedures to avoid or decrease protecting group manipulations have been developed for the synthesis of a single oligosaccharide or an oligosaccharide library,, such as glycosylation on unprotected or partially protected acceptors, and random glycosylation on unprotected acceptors. Thiem et al published reviews on random glycosylation in 2008, and glycosylation on unprotected acceptors in 2014.…”