Glycosylation Method Research Articles

Gold(I)-catalyzed synthesis of β-Kdo glycosides using Kdo ortho-hexynylbenzoate as donor

A gold(I)-catalyzed glycosylation of Kdo with glycosyl ortho-hexynylbenzoate as donor is reported. The couplings of Kdo ortho-hexynylbenzoate with a set of alcohols promoted by PPh3AuOTf afford Kdo glycosides with good β-selectivities. This glycosylation method allows for the synthesis of β-Kdo monosaccharide with a C5 linker at the reducing end for subsequent conjugation to carrier proteins and arrays.

A Direct Method for β-Selective Glycosylation with an N-Acetylglucosamine Donor Armed by a 4-O-TBDMS Protecting Group

A new direct method for β-selective glycosylation with an N-acetylglucosamine (GlcNAc) donor was developed. This substrate, which can be readily prepared from commercially available GlcNAc in two steps, contains a 4-O-tert-butyldimethylsilyl (TBDMS) protecting group as a key component. We found that this functionality could have a favorable effect on the reactivity of the GlcNAc donor. Glycosylation with the armed donor using primary alcohols in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in 1,2-dichloroethane smoothly gave the desired coupling products in good yields with complete β-selectivity, while sterically hindered acceptors were less efficient.

Regio- and stereoselective β-mannosylation using a boronic acid catalyst and its application in the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide derived from E. coli O75.

Regio- and stereoselective β-mannosylations using 1,2-anhydromannose and diol sugar acceptors in the presence of a boronic acid catalyst proceeded smoothly to give the corresponding β-mannosides with high regio- and β-stereoselectivities in high yields without further additives under mild conditions. In addition, this glycosylation method was applied successfully to the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide (LPS) derived from E. coli O75.

L‐Rhamnosylation: The Solvent is the Solution

Herein we present a systematic study of l‐rhamnosylation. The influence of protective groups, reactivity, solvents and glycosylation method, i.e. catalytic versus promoted glycosylation, are studied. It was found that the selectivity can be controlled to a large extend, by varying these parameters and hence the same donor can give both anomers. A reversal of the influence of the participating solvents is observed, and hence ethereal solvents increase the β selectivity, whereas nitrile solvents give almost exclusive α‐selectively.

Phthalic Anhydride-Mediated Direct Glycosylation of Anomeric Hydroxy Arabinofuranose: Synthesis of Repeating Oligoarabinofuranoside and Tetradecasaccharide Arabinan Motif of Mycobacterial Cell Wall

An efficient direct phthalic anhydride-mediated one-pot glycosylation method employing anomeric hydroxy arabinofuranose as glycosyl donor and triflic anhydride as activating agent has been developed. This method afforded the desired di- and oligoarabinofuranosides in good yields even in gram scale glycosylation when t-butylphthalic anhydride was used. Moreover, our new method can be further extended to the syntheses of repeating oligoarabinofuranoside and tetradecasaccharide arabinan motif found in mycobacterial cell wall.

Diversity synthesis of tetrahydroprotoberberines glycosides by combined chemical and microbial catalysis

The present study was designed to construct the structurally diverse library of tetrahydroprotoberberines (THPBs) by combining the methods of chemical nonselective demethylation and microbial glycosylation. HPLC-MS/MS analyses tentatively identified 12 de-methylated and 9 glycosylated derivates of THPBs and 5 rarely oxidized glycosides of THPBs in the library. Through this effort, we achieved not only a variety of the THPBs and their glycosides but also tested the catalytic characteristics and capabilities of G. deliquescens NRRL 1086.

Site-Directed Glycosylation of Peptide/Protein with Homogeneous O-Linked Eukaryotic N-Glycans.

Here we report a facile and efficient method for site-directed glycosylation of peptide/protein. The method contains two sequential steps: generation of a GlcNAc-O-peptide/protein, and subsequent ligation of a eukaryotic N-glycan to the GlcNAc moiety. A pharmaceutical peptide, glucagon-like peptide-1 (GLP-1), and a model protein, bovine α-Crystallin, were successfully glycosylated using such an approach. It was shown that the GLP-1 with O-linked N-glycan maintained an unchanged secondary structure after glycosylation, suggesting the potential application of this approach for peptide/protein drug production. In summary, the coupled approach provides a general strategy to produce homogeneous glycopeptide/glycoprotein bearing eukaryotic N-glycans.

ChemInform Abstract: Recent Progress in the Enzymatic Glycosylation of Phenolic Compounds

AbstractReview: 88 refs.

Glycosyl-Acceptor-Derived Borinic Ester-Promoted Direct and β-Stereoselective Mannosylation with a 1,2-Anhydromannose Donor.

β-Stereoselective mannosylations were conducted using a 1,2-anhydromannose donor and mono-ol acceptors in the presence of a glycosyl-acceptor-derived borinic ester. Reactions proceeded smoothly under mild conditions to provide the corresponding β-mannosides with high stereoselectivity in moderate to high yields. In addition, the present glycosylation method was applied successfully to the total synthesis of acremomannolipin A.

A selective and mild glycosylation method of natural phenolic alcohols.

Several bioactive natural p-hydroxyphenylalkyl β-D-glucopyranosides, such as vanillyl β-D-glucopyranoside, salidroside and isoconiferin, and their glycosyl analogues were prepared by a simple reaction sequence. The highly efficient synthetic approach was achieved by utilizing acetylated glycosyl bromides as well as aromatic moieties and mild glycosylation promoters. The aglycones, p-O-acetylated arylalkyl alcohols, were prepared by the reduction of the corresponding acetylated aldehydes or acids. Various stereoselective 1,2-trans-O-glycosylation methods were studied, including the DDQ–iodine or ZnO–ZnCl2 catalyst combination. Among them, ZnO–iodine has been identified as a new glycosylation promoter and successfully applied to the stereoselective glycoside synthesis. The final products were obtained by conventional Zemplén deacetylation.

Stereoselective Construction of β-Mannopyranosides by Anomeric O-Alkylation: Synthesis of the Trisaccharide Core of N-linked Glycans.

A new and efficient approach for direct and stereoselective synthesis of β-mannopyranosides by anomeric O-alkylation has been developed. This anomeric O-alkylation of mannopyranose-derived lactols is proposed to occur under synergistic control of a kinetic anomeric effect and metal chelation. The presence of a conformationally flexible C6 oxygen atom in the sugar-derived lactol donors is required for this anomeric O-alkylation to be efficient, probably because of its chelation with cesium ion. In contrast, the presence of a C2 oxygen atom plays a minor role. This glycosylation method has been successfully utilized for the synthesis of the trisaccharide core of complex N-linked glycans.

Stereoselective Construction of β‐Mannopyranosides by Anomeric O‐Alkylation: Synthesis of the Trisaccharide Core of N‐linked Glycans

AbstractA new and efficient approach for direct and stereoselective synthesis of β‐mannopyranosides by anomeric O‐alkylation has been developed. This anomeric O‐alkylation of mannopyranose‐derived lactols is proposed to occur under synergistic control of a kinetic anomeric effect and metal chelation. The presence of a conformationally flexible C6 oxygen atom in the sugar‐derived lactol donors is required for this anomeric O‐alkylation to be efficient, probably because of its chelation with cesium ion. In contrast, the presence of a C2 oxygen atom plays a minor role. This glycosylation method has been successfully utilized for the synthesis of the trisaccharide core of complex N‐linked glycans.

A versatile glycosylation strategy via Au(iii) catalyzed activation of thioglycoside donors.

Among various methods of chemical glycosylations, glycosylation by activation of thioglycoside donors using a thiophilic promoter is an important strategy. Many promoters have been developed for the activation of thioglycosides. However, incompatibility with substrates having alkenes and the requirement of a stoichiometric amount of promoters, co-promoters and extreme temperatures are some of the limitations. We have developed an efficient methodology for glycosylation via the activation of thioglycoside donors using a catalytic amount of AuCl3 and without any co-promoter. The reaction is very fast, high-yielding and very facile at room temperature. The versatility of this method is evident from the facile glycosylation with both armed and disarmed donors and sterically demanding substrates (acceptors/donors) at ambient conditions, from the stability of the common protecting groups, and from the compatibility of alkene-containing substrates during the reaction.

Synthetic investigation toward apigenin 5-O-glycoside camellianin B as well as the chemical structure revision.

Capitalizing on the Au(i)-catalyzed ortho-alkynylbenzoate glycosylation method, the first total synthesis of the proposed structure of apigenin-5-O-glycoside camellianin B was achieved, wherein three approaches, one linear and two convergent, were established, through which the synthetic structures were firmly corroborated. Meanwhile, through the synthesis of anthentic camellianin B via commercially available camellianin A, the misassigned structures of camellianins A and B were revised.

Temperature controlled stereoselectivity in the synthesis of 5-halo-2′-deoxyuridine derivatives

A series of α- and β-5-halo-2′-deoxyuridine derivatives were prepared with high anomeric selectivity using the conventional silylbase glycosylation method and taking advantage of the 3′-O-(N-acetyl)glycyl protection group and temperature control. Reactions performed at −7°C gave as much as 87% of the β-anomers, while an overnight reaction at 30°C gave up to 95% of the α-anomers.

Comparative Analysis of Fluorine‐Directed Glycosylation Selectivity: Interrogating C2 [OH → F] Substitution in d‐­Glucose and d‐Galactose

AbstractThe influence of C2 [OH → F] substitution on the stereochemical course of chemical glycosylation was interrogated in both D‐glucose and its C4 epimer D‐galactose. Molecular editing at C2 and configurational inversion at C4 were simultaneously investigated by variable‐temperature glycosylation studies of both systems. Extrapolation of the differences in enthalpic (ΔΔHβα‡) and entropic (ΔΔSβα‡) contributions that discriminate these closely similar systems revealed that deoxofluorination at the C2 position induces an enthalpic bias that augments β‐stereoselection. Intriguingly, the enhanced stereoselectivity of the C4 epimer D‐galactose was found to be entropic in nature. Given the prominence of these scaffolds in chemical biology, delineating the factors that underpin selectivity will be critical in developing novel glycosylation methods and in rationalizing differences with the natural systems post facto.

Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae

AbstractAll Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA‐derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.

Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug-Resistant Enterobacteriaceae.

All Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA-derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.

Regioselective and 1,2‐cis‐α‐Stereoselective Glycosylation Utilizing Glycosyl‐Acceptor‐Derived Boronic Ester Catalyst

AbstractRegioselective and 1,2‐cis‐α‐stereoselective glycosylations using 1α,2α‐anhydro glycosyl donors and diol glycosyl acceptors in the presence of a glycosyl‐acceptor‐derived boronic ester catalyst. The reactions proceed smoothly to give the corresponding 1,2‐cis‐α‐glycosides with high stereo‐ and regioselectivities in high yields without any further additives under mild reaction conditions. In addition, the present glycosylation method was successfully applied to the synthesis of an isoflavone glycoside.

Regioselective and 1,2-cis-α-Stereoselective Glycosylation Utilizing Glycosyl-Acceptor-Derived Boronic Ester Catalyst.

Regioselective and 1,2-cis-α-stereoselective glycosylations using 1α,2α-anhydro glycosyl donors and diol glycosyl acceptors in the presence of a glycosyl-acceptor-derived boronic ester catalyst. The reactions proceed smoothly to give the corresponding 1,2-cis-α-glycosides with high stereo- and regioselectivities in high yields without any further additives under mild reaction conditions. In addition, the present glycosylation method was successfully applied to the synthesis of an isoflavone glycoside.