New aspects of glycoside bond formation (original) (raw)

A new approach to the synthesis of glycosides

Pure and Applied Chemistry, 1993

An new approach towards glycosides, which obviates the use of promoters and depends upon the acihty of the glycosyl acceptor is proposed to achieve regioselective glycosidation. Glycosylidene mbenes, generated under thermal or photolytic conditions from 0benzylated or 0-acylated 1-azi-glycoses, or from glycono-l,5-(or 1,4)-lactone tosylhydrazones react with hydroxy compounds to yield glycosides. The preparation of these precursors, their structure, their thermal stability, and their products of thermolysis are discussed. A mechanism is proposed to explain and predict the reaction of 1-azi-glycoses with mono-, di-, and triols. Protonation of the carbene in the o-plane leads to an ion-pair, which cannot immediately form glycosides. The fate of this ion pair depends upon the pK of the glycosyl acceptor, inter-and intramolecular hydrogen bonds, the direction of H-bonds, the presence of a neighbouring group at C(2), the configuration of the glycosyl acceptor, the solvent, and the temperature. Strongly acidic hydroxy compounds give glycosides in high yields and stereoselectively. Successful regio-and stereoselective glycosidation of diols and triols depends strongly upon intra-(and inter)molecular hydrogen bonds, both between the hydroxy goups of the acceptor and between functional groups of the donor and hydroxy groups of the acceptor. This is illustrated by a number of significant cases. For some of them, regioselectivity is complementary to the one observed in glycosidations of the Koenigs-Knorr-type, for others it is not. Reasons for this are discussed. Other cases present the preferential glycosylation of secondary hydroxy groups in the presence of a primary one, and the selective formation of aD -glycosides of M A C and GlcNAc. Intramolecular reactions of alkoxyalkyl carbenes are illustrated by a new method for the formation of benzylidene acetals under basic conditions, and by a new synthesis of homobenzofurans. New reactions, leading to the formation of C,C bonds at the anomeric centre are presented: the synthesis of spiro-oxiranes, of dialkoxy-spiro-cyclo opanes, and of the first glycosylated, enantiomdcally pure derivatives of Cmbuckminst&erene.

Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions

Chemistry & Biology, 2014

This study describes the synthesis of the a-and b-linked N-acetyllactosamine (Galp-b-1,4-GlcNAc; LacNAc) glycosides of threonine (LacNAc-Thr). LacNAc-a-Thr was prepared by direct chemical coupling of a 2-azido-2-deoxy-lactose disaccharide donor to a suitable partially protected threonine unit. In contrast, stepwise chemical generation of b-linked N-acetylglucosamine followed by enzymatic galactosylation to give LacNAc-b-Thr proved effective, whereas use of a 2-azido-2-deoxy-lactose donor in acetonitrile failed to give the desired b-linked disaccharyl glycoside. This study illustrates that it is possible to overcome the inherent stereoselection for 1,2-trans chemical glycosylation with a GlcNAc donor, and that the well-established preference of bovine b-1,4-galactosyltransferase for b-linked acceptor substrates can also be overcome. Using this knowledge, short glycopeptide fragments based on T. cruzi mucin sequences, Thr-Thr-[LacNAcThr]-Thr-Thr-Gly, were synthesised. All LacNAc-based compounds outlined were shown to serve as acceptor substrates for sialylation by T. cruzi trans-sialidase. † The a-glycoside appears to be formed directly, not through equilibration of the b-glycoside. Addition of pure b-glycoside to the reaction mixture did not result in additional a-glycoside formation. straightforward and direct approach to the a-linked GlcNAc-Thr system that, given that there is no need to manipulate C-2 functionality, is competitive with other approaches to such a-linked 2-amino-2-deoxy-glucosides. 30,31 Removal of the benzyl ester and Fmoc groups from protected glyco-amino acids (9) and (10) was performed by standard hydrogenation (10% Pd-C/H 2 ); subsequent removal of the acetate groups was realised in the presence of 1 M NaOMe in MeOH. In this way, 20-30 mg quantities of the completely deprotected glyco-amino acids (3) were obtained (Scheme 1).

]A potentially versatile synthesis of glycosides

Carbohydrate Research, 1973

Phenyl I-thio-D-glucopyranosides in the presence of mercury(H) salts are readily solvolysed to give all@ D-glucopyranosides with inverted anomeric configuration. Methanolyses of the #? and CI anomers afford the methyl tl-and p-glycosides which were isolated in yields of 74 and 87%, respectively; n.m.r. examinations indicated that, whereas the /?-glycoside was produced stereospecifically, the a-glycoside was formed together with-6% of its /I isomer. The approach can be extended to the synthesis of complex glycosides (the a anomers of which are of special interest) as was illustrated by the preparation of cholestanyl and 1-naphthyl a-o-glucopyranoside and a disaccharide derivative.

Recent progress in the field of glycoconjugates

Carbohydrate Research, 2014

The ubiquity of glycoconjugates in nature and their role in different biological processes, has led to the development of several methodologies to synthesize these molecules. Synthetic glycoconjugates are now used to answer a variety of glycoconjugate-related biological questions and has provided new potential vaccines against cancer, viral and bacterial infections and new biotechnological tools. This review aims to collect and compile the recent advances in the field of glycopeptides, glycoproteins and glycolipid synthesis and also to update the previous reviews made on this subject. Finally, by highlighting the successes and failures of past research, we hope that this review will inspire fruitful research in this important medicinal chemistry field.

New schemes for the synthesis of glycolipid oligosaccharide chains

Pure and Applied Chemistry, 2000

The driving force for the constant improvement and development of synthetic methodologies in carbohydrate chemistry is the importance of natural oligosaccharide chains in numerous biological phenomena such as cell growth, differentiation, adhesion, etc. Here, we report our syntheses of the spacer-armed oligosaccharides of sialylated