Polymer-supported Oligosaccharide Synthesis Research Articles

Reductive deprotection of propargyl ether by a SmI 2–amine–water system and its application to polymer-supported oligosaccharide synthesis

A SmI 2–amine–water system instantaneously deprotected aryl and alkyl propargyl ethers in a reductive manner. The utility of the propargyl group as a protecting group in oligosaccharide synthesis, and its application to polymer-supported oligosaccharide synthesis is described.

Polymer-supported oligosaccharide synthesis using ultrafiltration methodology

Polymer-supported oligosaccharide synthesis was carried out using an ultrafiltration technique in which the synthesized polymer-bound oligosaccharides were separated from the other reagents by ultrafiltration though membranes with specifically sized pores.

Synthesis of Oligosaccharides on Soluble High‐Molecular‐Weight Branched Polymers in Combination with Purification by Nanofiltration.

An efficient approach for polymer-supported oligosaccharide synthesis is described whereby branched and high-molecular-weight PEG derivatives are used in combination with purification by nanofiltration. This methodology was applied to the preparation of a tetraglucoside and the tumor-associated antigen Lex.

Synthesis of oligosaccharides on soluble high-molecular-weight branched polymers in combination with purification by nanofiltration.

[structure: see text] An efficient approach for polymer-supported oligosaccharide synthesis is described whereby branched and high-molecular-weight PEG derivatives are used in combination with purification by nanofiltration. This methodology was applied to the preparation of a tetraglucoside and the tumor-associated antigen Le(x).

1-Methyl 1′-cyclopropylmethyl: an acid labile O-protecting group for polymer-supported oligosaccharide synthesis

R, S-1-Methyl 1′-cyclopropylmethanol can be converted to its trichloroacetimidate derivative. Lewis acid catalyzed etherification can then be used to prepare methyl cyclopropylmethyl (MCPM) ethers. Thus, ethyl 2,3,4-tri- O-benzyl-6- O-( R, S-1-methyl 1′-cyclopropylmethyl)-1-thio-α/β- d-glucopyranoside was prepared and the linker polymer combination (MPEG)(DOX)OH glycosylated. The MCPM group was cleaved with 10% trifluoroacetic acid in CH 2Cl 2 and the resulting alcohol glycosylated. After protecting group manipulations and cleavage the peracetylated disaccharide GlcNAc(β1→6)GlcOAc was isolated. Similarly the 4,6- O-phenylboronate diester of ethyl 1-thio-β- d-galactopyranoside was regioselectively etherified at O-3 and after boronate cleavage the sugar benzoylated to give ethyl 2,4,6-tri- O-benzoyl-3- O-( R, S-1-methyl 1′-cyclopropylmethyl)-1-thio-β- d-galactopyranoside. Through a similar sequence of glycosylation of (MPEG)(DOX)OH, MCPM deprotection, glycosylation, functional group manipulation and cleavage the peracylated disaccharide GlcNAc(β1→3)Gal(β1→)DOXOAc was prepared. Finally, the donor 2,6-di- O-benzoyl-4- O-levulinoyl-3- O-( R, S-1-methyl 1′-cyclopropylmethyl)-1-thio-β- d-galactopyranoside was prepared and elaborated into the trisaccharide GlcNAc(β1→3)[Glc(β1→4)]Gal(β1→)DOXOH. This trisaccharide was elaborated into the pentasaccharide Neu5Ac(α2→3)Gal(β1→4)GlcNAc(β1→3) [Glc(β1→4)]Gal(β1→)DOXOH using GalE-LgtB fusion and CMP-Neu5Ac synthetase/sialyltransferase fusion enzymes. This pentasaccharide is a single repeat unit of the capsular polysaccharide of Group B Streptococcus type 1A.

Polymer-supported oligosaccharide synthesis by a loading–release–reloading strategy

A new synthetic strategy for solid-supported oligosaccharide synthesis has been developed whereby a synthetic intermediate can be released from the solid support, purified and reloaded for further synthesis. Key to the success of this approach is the polymeric support polystyrylboronic acid, which allows saccharides to be loaded by heating in pyridine and released by treatment with a mixture of acetone and water.

Recent Progress in Polymer-Supported Synthesis of Oligosaccharides and Carbohydrate Libraries

Glycobiology is a rapidly evolving field and tackles many phenomena of biomedical importance. Driven by the need to create more efficient methods for the synthesis of complex oligosaccharides, the last few years have seen a major push toward a general approach amenable to solid-phase synthesis. Different strategies have been explored and a host of glycosylating agents have been investigated. New linker systems, different solid support materials and a variety of protective groups have been evaluated. The development of on-resin analytical techniques such as MAS-NMR have greatly facilitated the development of new methods for solid-phase oligosaccharide synthesis. These methodological advances have been demonstrated by preparation of several complex oligosaccharides. As the coupling yields have been improved to 95% and above, the desired products could be obtained in good yield even after seven glycosylations. In addition to single target structures, carbohydrates have generated rapidly increasing interest with respect to sets of diverse, carbohydrate containing molecules. These efforts are of increasing importance for providing molecular tools to elucidate biological processes. While much has been achieved to date, the difficulties encountered in the solid-phase assembly of oligosaccharides underscore the need for the developments of all facets of carbohydrate chemistry. Given the rapid progress in the past eight years, it is conceivable that the synthesis of ‘simple’ oligosaccharides may soon be automated. Careful investigations into many parameters will eventually allow the synthetic chemist to enable even non-specialists to create important tools for biochemical, biophysical, and medical applications.

Acyl Transfer as a Problematic Side Reaction in Polymer-Supported Oligosaccharide Synthesis

Under a wide variety of glycosylation conditions acyl transfer to the polymer support competed with glycoside formation, including the pivaloyl protecting group. As well as acyl transfer, many glycosylations also led to the formation of polymer-bound β-1,2-linked oligomers of the donor. Using ethyl 2,6-di-O-pivaloyl-3,4-O-isopropylidene-β-d-galactothiopyranoside as donor under promotion of N-iodosuccinimide/silver trifluoromethanesulfonate in the presence of 2-methyl-2-butene, an 82% yield of glycoside was obtained along with pivaloylated polymer. Subsequent work showed that increasing the steric bulk about the alcoholic acceptor in conjunction with this 2-O-pivaloyl-protected glycosyl donor completely suppresses this side reaction, giving a nearly quantitative yield of glycoside. This contraintuitive approach of decreasing the reactivity of both the donor and the acceptor to minimize a side reaction is rationalized by assuming that the barrier to acyl transfer is more sensitive to the protecting groups than that of glycosylation. These developments led to a polymer-supported synthesis of the branch point trisaccharide of the group B type 1A Streptococcus capsular polysaccharide.

Beneficial participation of the polymer: Improvement in polymer-supported oligosaccharide synthesis

The reagent combination scandium(III) trifluoromethanesulfonate and acetic anhydride efficiently cleaves oligosaccharides bound to the polyethylene glycol (PEG) polymer-support via the dioxyxylene (DOX) linker. Unexpectedly, the site cleavage is between the DOX linker and the PEG polymer. This method of cleavage allows for the use of DOX as a linker for synthesis on polystyrene-polyethylene glycol, PS- PEG beads.

Glycosylation reactions--present status future directions.

A short review of the present status of glycosylation reactions is presented. The reactivity of both proven and newer glycosylation methods are briefly discussed. Emphasis is placed on the control of stereochemistry and regiochemistry. As well, the identification and avoidance of side reactions is covered. Polymer-supported synthesis of oligosaccharides is noted as a promising direction for eliminating some of the problems associated with purification. It is suggested that a better understanding of the mechanism of glycosylation reactions is necessary for future improvements to stereoselectivity and regioselectivity. A key advance would be methods for enhancing the reactivity of weakly nucleophilic hydroxyls.

Synthesis of oligosaccharides, glycopeptides, and glycolipids

Some novel concepts and recent developments in oligosaccharide and glycoconjugate synthesis are presented and discussed. The selective activation of one of a mixture of two or more glycosyl donors provides access to oligosaccharides while minimizing the number of manipulations required at the anomeric centers. A new method for sialylation using glycosyl phosphites is also presented. Developments in enzymatic glycosylation include in situ cofactor regeneration and the synthesis of unnatural glycosides. Recent applications of the above methods are the synthesis of sially Lewis X, ciclamycin O, and calicheamicin and the development of a strategy for polymer-supported oligosaccharide synthesis. Some recently reported methods for synthesizing glycosylamino acids as structural subunits of glycopeptides are also discussed.