Glycosylation Using a Thioglycoside and Methyl Trifluoro-Methanesulfonate. A New and Efficient Method for CIS and Trans Glycoside Formation

Abstract

For the synthesis of large oligosaccharides and biologically active oligosaccharide derivatives it is often desirable to use a block synthesis, that is to link an oligosaccharide residue to another or to a non-carbohydrate aglycon. It is sometimes difficult to prepare glycosyl halide derivatives of the oligosaccharides in good yields, and there is a need for glycosylating agents which can be prepared under mild conditions and in good yields.     

Synthesis of differentially protected ribitol derivatives from 3,4-O-benzylidene-d-ribono-1,5-lactone

Several differentially protected ribitol derivatives were synthesised using 3,4-O-benzylidene-d-ribono-1,5-lactone as versatile starting compounds for oligosaccharide synthesis. The obtained ribitol derivatives allow the regiospecific coupling of glycosyl donors to either of the hydroxyl groups of ribitol and can be applied for the preparation of polyhydroxylated compounds.     

N-Bromosuccinimide-Mediated Conversion of Allyl Glycosides to Glycosyl Hemiacetals

A novel reaction condition has been developed for the hydrolysis of differentially functionalized allyl glycosides to their corresponding glycosyl hemiacetal derivatives in the presence of N-bromosuccinimide (NBS). The reaction condition is exceptionally fast, mild, and compatible with most of the functional groups used in the oligosaccharide synthesis, and yields were excellent.     

Combinatorial synthesis of an oligosaccharide library by using beta-bromoglycoside-mediated iterative glycosylation of selenoglycosides: rapid expansion of molecular diversity with simple building blocks

A new method for constructing an oligosaccharide library composed of structurally defined oligosaccharides is presented based on an iterative glycosylation of selenoglycosides. Treatment of 2-acyl-protected selenoglycosides with bromine selectively generates beta-bromoglycosides, which serve as glycosyl cation equivalents in the oligosaccharide synthesis. Thus, the coupling of the bromoglycosides with another selenoglycoside affords the corresponding glycosylated selenoglycosides, which can be directly used to next glycosylation. The iteration of this sequence allows the synthesis of a variety of oligosaccharides including an elicitor active heptasaccharide. A characteristic feature of the iterative glycosylation is that glycosyl donors and acceptors with the same anomeric reactivity can be selectively coupled by activation of the glycosyl donor prior to coupling with the glycosyl acceptor. Therefore, same selenoglycosides can be used for both the glycosyl donors and the acceptors. This feature has been exemplified by a construction of an oligosaccharide library directed to elicitor-active oligosaccharides. The library composed of stereochemically defined oligoglucosides with considerable structural diversity can be constructed starting from simple selenoglycosides.     

Divergent heparin oligosaccharide synthesis with preinstalled sulfate esters

Traditional chemical synthesis of heparin oligosaccharides first involves assembly of the full length oligosaccharide backbone followed by sulfation. Herein, we report an alternative strategy in which the O-sulfate was introduced onto glycosyl building blocks as a trichloroethyl ester prior to assembly of the full length oligosaccharide. This allowed divergent preparation of both sulfated and non-sulfated building blocks from common advanced intermediates. The O-sulfate esters were found to be stable during glycosylation as well as typical synthetic manipulations encountered during heparin oligosaccharide synthesis. Furthermore, the presence of sulfate esters in both glycosyl donors and acceptors did not adversely affect the glycosylation yields, which enabled us to assemble multiple heparin oligosaccharides with preinstalled 6-O-sulfates.     

Synthesis of Oligosaccharide Structures from the Lipopolysaccharide of Moraxella catarrhalis

The synthesis of the octasaccharide [p-(trifluoroacetamido)phenyl]ethyl 4-O-[2-O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-beta-D-glucopyranosyl]-6-O-[2-O-[4-O-(4-O-alpha-D-galactopyranosyl-beta-D-galactopyranosyl)-alpha-D-glucopyranosyl]-beta-D-glucopyranosyl]-3-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside, representing the outer part of the lipooligosaccharide from Moraxella catarrhalis serotype A, is described, together with a hepta-, a hexa-, and a pentasaccaride, composing parts thereof with shorter oligosaccharide chains substituted in the 6-position of the central 3,4,6-branched glucose moiety. The versatility of the use of thioglycosides in oligosaccharide synthesis is shown, since throughout the synthesis thioglycosides are used as glycosyl donor precursors, either directly in dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling reactions or after conversion to the corresponding glycosyl bromide in silver triflate-promoted couplings. The effects of different protecting groups, anomeric leaving groups, and solvents used in the various coupling reactions are often substantial, which necessitates the use of easily convertible intermediates.     

Lactonization-mediated glycosylations and their application to oligosaccharide synthesis

The concept of lactonization-mediated and related glycosylations led us to develop new methods of glycosylation such as the 2'-carboxybenzyl (CB) glycoside method, the glycosyl pentenoate/phenylselenyl trifluoromethanesulfonate (PhSeOTf) method, and the glycosyl aryl phthalate method. Highly stereoselective beta-mannopyranosylations were achieved by employing the CB glycoside and the glycosyl pentenoate/PhSeOTf methods. The CB glycoside method was also utilized for stereoselective 2-deoxyglycosylation, beta-arabinofuranosylation, and alpha-galactofuranosylation. In addition, these lactonization-mediated methods of glycosylation were employed for the synthesis of complex oligosaccharides. In particular, the CB glycoside method was successfully applied to the synthesis of repeating oligosaccharide subunits of the O-polysaccharide of the lipopolysaccharide from Danish Helicobacter pylori strains and Escherichia coli 077, the synthesis of oligoarabinofuranosides in mycobacterial cell walls, and the total synthesis of antineoplastic agelagalastatin.     

Synthesis of a Heptasaccharide,Structurally Related to the Phytoelicitor Active Glucan of Phytophthora Megasperma F.SP. Glycinea

Abstract

A synthesis is described of the heptasaccharide 1, which may form part of the phytoelicitor-active glucan of Phytopkthora megasperma f. sp. glycinea. Silver triflate was used as the promoter in Koenigs-Knorr type condensations using glycosyl bromides, each with a participating benzoyl group in the 2-position, for the synthesis of the smaller oligosaccharide fragments. For joining the larger ones, methyl triflate was used as the promoter and an oligosaccharide thioglycoside carrying a participating benzoyl group in the 2-position was used as the glycosyl donor.     

Glycosyl thioimidates as versatile building blocks for organic synthesis

This review discusses the synthesis and application of glycosyl thioimidates in chemical glycosylation and oligosaccharide assembly. Although glycosyl thioimidates include a broad range of compounds, the discussion herein centers on S-benzothiazolyl (SBaz), S-benzoxazolyl (SBox), S-thiazolinyl (STaz), and S-benzimidazolyl (SBiz) glycosides. These heterocyclic moieties have recently emerged as excellent anomeric leaving groups that express unique characteristics for highly diastereoselective glycosylation and help to provide a streamlined access to oligosaccharides.     

4-(pyridin-2-yl)thiazol-2-yl thioglycosides as bidentate ligands for oligosaccharide synthesis via temporary deactivation

This study focusses on a new concept for oligosaccharide synthesis based on 4-(pyridin-2-yl)thiazol-2-yl thioglycosides that can either act as effective glycosyl donors or can be deactivated by stable bidentate complexation with palladium(II) bromide.     

N-benzyl-2,3-oxazolidinone as a glycosyl donor for selective alpha-glycosylation and one-pot oligosaccharide synthesis involving 1,2-cis-glycosylation

Glycosylation reactions using N-benzyl-2,3-trans-oxazolidinones as the glycosyl donors were shown to be highly alpha-selective. Advantages of the donor include facile preparation in gram-scale preparation and simple deprotection procedures. Subsequently, a one-pot oligosaccharide synthesis involving 1,2-cis glycosidic linkages was demonstrated using the novel glycosyl donors.     

Rapid assembly of oligosaccharides: 1,2-diacetal-mediated reactivity tuning in the coupling of glycosyl fluorides

This paper describes the application of 1,2-diacetal protecting groups to control the reactivity tuning of glycosyl fluorides in oligosaccharide coupling reactions. The synthetic potential of this new methodology is demonstrated by the ‘one-pot’ synthesis of a linear pentasaccharide and the efficient assembly of the core oligosaccharide of the GPI anchor of yeast (Saccharomyces cerevisiae).     

Silver Triflate. A Mild Alternative Catalyst for Glycosylation Conditions Using Trichloroacetimidates as Glycosyl Donors

Although trimethylsilyl triflate (TMSOTf) has been widely used to promote glycosyl trichloroacetimidates in oligosaccharide synthesis, silver triflate (AgOTf) was proved to be a mild and in some cases more efficient catalyst in TMSOTf‐sensitive glycosylations. Migration and degradation in some specific coupling reactions can be reduced significantly under this alternative glycosylation condition.     

Going to extremes: "super" armed glycosyl donors in glycosylation chemistry

This concept article gives an overview of stereoelectronic effects in monosaccharide systems and how these can be used to dramatically enhance the reactivity of glycosyl donors in oligosaccharide synthesis.     

Hydrogen Bond Mediated Aglycone Delivery: Synthesis of Linear and Branched α‐Glucans

A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the synthesis of α‐glucans, which are abundant in nature, but as targets represent a notable challenge to chemists. The synthesis of linear oligosaccharide sequences was accomplished in complete stereoselectivity in all glycosylations. The efficacy of HAD may diminish with the increased bulk of the glycosyl acceptor, and may be an important factor for the syntheses of oligomers beyond pentasaccharides. The synthesis of a branched structure proved more challenging, particularly with bulky trisaccharide acceptors.     

Wang resin-type linker containing a nitro group for polymer support oligosaccharide synthesis: polymer-supported glycosyl donor

A nitro-introduced Wang resin-type linker for soluble and insoluble polymer support oligosaccharide synthesis is described. The linker was used for connecting glycosyl donors and polymer supports, and was completely stable under the glycosylation conditions tested. The cleavage of the linker was performed under reductive conditions without affecting the protecting groups to release disaccharides.     

Oligosaccharide relative quantitation using isotope tagging and normal-phase liquid chromatography/mass spectrometry

The growing interest in the conversion of plant biomass into biofuels has recently highlighted the lack of analytical techniques that are able to profile the fine structures of plant cell-wall polysaccharides. Here we present a new liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) platform called Oligosaccharide Quantitation using Isotope Tagging (OliQuIT) developed for profiling the oligosaccharides derived from glycosyl hydrolase digestion of polysaccharides. The method is demonstrated using different arabinoxylan-derived oligosaccharide samples, which are reductively aminated with either the light (12C6) or heavy (13C6) form of aniline. The complex oligosaccharide mixtures are analysed by capillary normal-phase (NP)-LC and ESI-MS. Importantly, arabinoxylan oligosaccharide isomers are separated by NP-LC and their relative abundance in different samples can be determined from the intensities of ions labeled with the different isotopes. OliQuIT will be of use in multiple applications, including screening for plant varieties with improved saccharification properties, characterizing glycosyl hydrolase specificities and analysing plant glycosyl transferase mutants.     

Rapid synthesis of oligosaccharide moieties of globotriaosylceramide using fluorous protective group

The use of the Bfp (bisfluorous chain type propanoyl) group as a fluorous protective group made it possible to rapidly synthesize galabiose and the Gb3 oligosaccharide derivatives by a simple fluorous-organic extraction purification. The fluorous oligosaccharide synthesis using the Bfp group is an excellent strategic alternative to solid phase oligosaccharide synthesis, and removes some of the disadvantages of the solid phase method.     

Glycosyl alkoxythioimidates as complementary building blocks for chemical glycosylation

It is reported that S-glycosyl O-methyl phenylcarbamothioates (SNea carbamothioates) have a fully orthogonal character in comparison to S-benzoxazolyl (SBox) glycosides. This complete orthogonality was revealed by performing competitive glycosylation experiments in the presence of various promoters. The results obtained indicate that SNea carbamothioates have a very similar reactivity profile to that of glycosyl thiocyanates, yet are significantly more stable and tolerate selected protecting group manipulations. These features make the SNea carbamothioates new promising building blocks for further utilization in oligosaccharide synthesis.     

Solid-phase synthesis of complex oligosaccharides using a novel capping reagent

Solid-phase-supported oligosaccharide synthesis of a core N-glycan tetrasaccharide and of a trisaccharide containing the Galili antigen is reported. The synthesis is based on a hydroxymethylbenzyl benzoate spacer-linker system attached to the Merrifield resin, O-Fmoc-protected O-glycosyl trichloroacetimidates as glycosyl donors, and benzoyl isocyanate as a capping reagent for low-reactivity hydroxy groups. In this way, the target molecules could be efficiently obtained with little byproduct formation, and hence final purification was convenient.