Stereoselective Glycosylation of Glucosamine: The Role of the N‐Protecting Group

Abstract

Oligosaccharides and glycoconjugates play an important role in biological processes. The use of these complex polymers as biocompatible materials for medicinal applications as well as therapeutic agents for the treatment of several diseases has attracted considerable interest. However, these investigations require large and pure amounts of glycostructures. Glucosamine is one of the major building blocks of these highly important glycoconjugates. Recently, considerable synthetic efforts have been devoted to improving stereoselective glycosylation. In this Focus review, the role of the amine protecting group in the outcome of the glucosamine glycosylation reaction is highlighted.

Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine

“…Fort he CDE branching trisaccharide,w ee nvision the Eu nit should be installed onto Df irst before Cast he 4-OH of Dm ay be too hindered if the 6-OH of Di sg lycosylated first. To facilitate the formation of 1,2-trans linkage between Ca nd D, Tr oc, which is regarded as ap articipating neighboring group, [19,20] was used as the N-protective group for 2-amine of Cu nit fucosamine (building block 4). Theg lycosyl linkage between amino-mannuronic acid Band fucosamine Cwas challenging to form directly due to the generally low reactivities of uronic acid donors and the 1,2-cis stereochemistry of the linkage.W e opted for an indirect route using the 3-amino glucose derivative 5 as surrogates of amino-mannuronic acid.…”

Modulating glycosylation with exogenous nucleophiles: an overview

“…[10][11][12] Despite impressive progress in the recent development of glycosylation methods, the synthesis of a newly identified oligosaccharide compound or glycoconjugate still requires a new set of reaction conditions and glycosyl building blocks, which render the synthesis time-consuming and inefficient. 8,[13][14][15][16] The major challenge in carbohydrate synthesis is the stereochemical control of glycosidic bond formation. This issue is further complicated by the diverse structure of oligosaccharides and a wide variety of monosaccharide units.…”

Advances in Stereoselective 1,2‐cisGlycosylation using C‐2 Auxiliaries

“…A)C-2 acyl participation reliably affords 1,2-trans glycosides( 4), B)Achiral S-configured auxiliary affords1 ,2-cis glycosides (9)v ia a trans-configured sulfonium ion (8) C)Achiral Rconfigured auxiliary affords 1,2-trans glycosides (14)via a cis-configured sulfonium ion (12). [9] In contrast, the introductiono f1 ,2-cis glycosidic linkages is much more challenging and requires glycosyl donors having a non-assisting functionality at C-2. Furthermore, this strategy is also applicable to the synthesis of 2-deoxy-2-amino-glycosides using amine-protecting groups that can performN GP.H owever, care needs to be taken when using an N-acetyl group for NGP as the corresponding glycosyl oxazoline is ac ommonly formed byproduct, but can be avoided by using Lewis acid catalysis.…”

“…[8] Alternatively,o ther amine protecting groups that can perform NGP such as phthalimido, tetrachlorophthalimido, trichloroacetyl, allyloxycarbonyl, and 2,2,2-trichloroethyloxycarbonyl can be used. [9] In contrast, the introductiono f1 ,2-cis glycosidic linkages is much more challenging and requires glycosyl donors having a non-assisting functionality at C-2. [6] In general,t hese glycosylations are less selectivea nd requireo ptimizationt oa chieve acceptablea nomeric ratios.R ecent advances in anomeric control have led to new methodologies to synthesize 1,2-cis linkages of monosaccharides such as glucose, galactose, mannose, [10] glucosamine, [11] galactosamine, [12] and furanose sugars.…”