A Modular Approach for the Synthesis of Oligosaccharide Mimetics

Patel, A.; Lindhorst, Thisbe K.

doi:10.1021/jo005671u

Cited by 34 publications

(18 citation statements)

References 28 publications

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“…[16] This approach utilizes the potential for bifunctionalization of 6-amino-6-deoxy glycosides by addressing the terminal amino group in a manner analogous to a Michael reaction. Firstly, through the use of a stoichiometric amount of freshly distilled methyl acrylate in methanol, the 6-amino-functionalized mannoside 1 [17] was converted into ester 2, which can be used as a carbohydrate scaffold for the subsequent syntheses of glycolipid mimetics (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters

et al. 2006

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Glycolipids are involved in many cellular recognition processes, so there is a need for their synthesis as well as for the design and preparation of glycolipid mimetics. In addition to the application of glycolipid mimetics in a glycobiological context, they are also of interest in many other fields of research, due to their amphiphilic characters. Our goal was to elaborate a series of known orthogonally functionalized glycomimetics and cluster glycosides into glycomimetics of a glycolipid type, so monosaccharide building blocks such as 3, glycodendrons such as 19, and branched cluster glycosides of the type 24 were ligated with lipophilic molecules by peptide coupling, this conjugation providing a new class of complex amphiphilic glycoconjugates with high molecular diversity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Resultsmentioning

confidence: 99%

Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters

et al. 2006

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“…This finding supports recent studies7, 14 on the biological role of 6‐sulfo‐sLe X tetrasaccharides and GlcNAc‐6‐ O ‐sulfotransferases. Just recently, Patel and Lindhorst reported their module approach for the synthesis of oligosaccharide mimics 15. Although their approach is based on the assembly of different sugar epitopes on dendric glycoconjugates and may be discriminated in principle from ours, these approaches will provide a promising pathway to construct artificial glycoconjugates with high biological potential.…”

Section: Methodsmentioning

confidence: 99%

Facile Assembly of Cell Surface Oligosaccharide Mimics by Copolymerization of Carbohydrate Modules

Sasaki

Nishida

Tsurumi

et al. 2002

Angewandte Chemie Intl Edit

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Artificial glycoconjugate polymers (glycopolymers) and other multivalent carbohydrate ligands constitute a new class of biomimetic supramolecules. [1] They have shown many biological applications in, for example, cultivation, tumor diagnosis and detection, and the trapping of viruses and bacterial toxins. [2] Their utility is ascribed mainly to their strong and species-specific interactions with the receptor proteins as a result of multivalent binding and/or carbohydrate cluster effects. Although most of the glycopolymers so far prepared and applied were made up of simple mono-and disaccharides, more intense interest has been directed to glycopolymers carrying cell-surface oligosaccharides such as sialyl Lewis X (sLe X ) [3] and globosyl oligosaccharides [4] that have potentially greater biological significance. From a practical viewpoint, however, the synthesis and application of these glycoconjugates are seriously restricted by the difficulty in preparing target oligosaccharides in sufficient amounts prior to their incorporation into the multivalent models.In the course of our synthetic study of glycopolymers carrying the mimics of cell-surface oligosaccharides, [5] we found recently that an acrylamide copolymer carrying a-l-fucopyranoside and 3-sulfo-b-d-galactopyranoside as a side chain shows strong activity in blocking L-selectin/sLe X tetrasaccharide adhesion. [6] As judged from the observation that none of the acrylamide copolymers carrying only one of the two glycosides showed a notable activity, the observed activity was ascribed to the cooperative binding of the a-lfucoside and 3-sulfo-b-d-galactoside to L-selectin. This finding indicated the potential utility of the module approach and prompted us to generalize it as a ™carbohydrate module method∫.For the facile understanding of our ™carbohydrate module method∫, let us assume a model consisting of the binding of a branching pentasaccharide with the receptor protein (Figure 1). In this model the two glycoside residues (A1 and A2) at the nonreducing terminal provide key binding interactions with the receptor protein at the r(A1) and r(A2) binding sites. Conventional mimic syntheses may target a branching trisaccharide carrying A1, A2, and B residues, thus developing the multivalent model (polymer-(A1 þ A2 þ B)) in Figure 1 b. Our approach targets a copolymer-(A1/A2) species carrying the key interactive sugars (Figure 1 c) to circumvent the difficulty in preparing the branching saccharide. The copolymer-(A1/A2) species is assumed to have a certain probability of occupying both of the binding sites and, thus, is expected to show a higher binding activity than the polymers carrying only one of the key sugars (poly-(A1) and poly-(A2)). This situation means that copolymerization of two key interactive sugars (A1 and A2 in the present case) provides a facile way to mimic the biologically active structures of oligosaccharides. The glycopolymers thus derived may show potent biological activity in blocking the binding of the oligosaccharide to receptor proteins...

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“…Examples of thiourea-connected saccharides have been typically limited to compounds where the tethering reaction involves only two moieties, with no possibility of chain elongation [68,70–72 81], except in cases where there are spacer substituents [82]. Interestingly, a thiourea-linked dinucleotide was elongated by solid-phase synthesis to incorporate positively charged isothiouronium inter-nucleoside linkages into otherwise negatively charged DNA (Fig.…”

Section: Reviewmentioning

confidence: 99%

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

Blanco¹,

Ortega‐Caballero²,

Fernández³

2010

Beilstein J. Org. Chem.

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SummaryOligosaccharides are currently recognised as having functions that influence the entire spectrum of cell activities. However, a distinct disadvantage of naturally occurring oligosaccharides is their metabolic instability in biological systems. Therefore, much effort has been spent in the past two decades on the development of feasible routes to carbohydrate mimetics which can compete with their O-glycosidic counterparts in cell surface adhesion, inhibit carbohydrate processing enzymes, and interfere in the biosynthesis of specific cell surface carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties.

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A Modular Approach for the Synthesis of Oligosaccharide Mimetics

Cited by 34 publications

References 28 publications

Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters

Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters

Facile Assembly of Cell Surface Oligosaccharide Mimics by Copolymerization of Carbohydrate Modules

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

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