Glycosidation Reactions Research Articles

Synthesis of the mixed acetal segment of S-glyceroplasmalopsychosine

In this report the concept of converting carbohydrate to non-carbohydrate asymmetric molecules has been successfully exploited. The mixed acetal segment of glyceroplasmalopsychosine, a novel glycolipid, has been synthesized in a stereospecific manner using two simple sugar units. The glycosidation reaction between these two monosaccharides ensured the correct acetal stereocenter of the target molecule. Either olefin metathesis or heterogeneous Wittig reactions were used for constructing the long aliphatic chain of glyceroplasmalopsychosine.

Syntheses and Glycosidation Reactions of 6-Thiosialosyl Donors

Syntheses and Glycosidation Reactions of 6-Thiosialosyl Donors

Syntheses of 5-Thio-D-Mannose from Petrochemicals and a Disaccharide Analog Containing It

Per-O-acetyl-5-thio-DL-mannose was synthesized from petrochemicals in six steps and 9% overall yield. It was then derivatized into glycosyl trichloroacetimidate and subjected to glycosidation reaction with a mannosyl acceptor to give a separatable mixture of disaccharides with 5-thio-D- and L-mannosides. This is the first synthesis of an enantiomerically pure 5-thiosugar derivative from racemic chemicals. The D-glycoside was derivatized into methyl (5-thio-α-D-mannopyranosyl)-2-O-α-D-mannopyranoside 6-phosphate as a potential inhibitor of a golgiα-1,2-mannosidase.

Development of a Scaleable Process for the Synthesis of the A2a Agonist, UK-371,104

The development and utilization of a scaleable process for the manufacture of the A2a agonist UK-371,104 (1) is described. Key steps in the synthesis include (i) a palladium-catalyzed cyanation reaction to prepare the nitrile 10, (ii) a telescoped conversion of the acid 11 to the glycosidation substrate 9, and (iii) the stereoselective coupling of 8 with 9 in a glycosidation reaction mediated by TMS triflate in 1,2-dimethoxyethane followed by conversion through to 1.

Introduction of Vinyl and Hydroxymethyl Functionalities at C-4 of Glucose-Derived Substrates: Synthesis of Spirocyclic, Bicyclic, and Tricyclic Nucleosides

Installing hydroxymethyl and hydroxyethyl substitutions at C-4 through vinylation and hydroboration-oxidation reactions of the C-4 bis-hydroxymethyl derivative of d-glucose based substrate, and inserting heteroatoms thereafter permitted formation of N-, O-, or S-heterocycles leading to [4,5]- or [5,5]-spirocycles and a bicyclo[3.3.0]octane product. Some of the spirocycles were converted to spironucleosides under Vorbruggen glycosidation reaction conditions. Similarly, the bicyclic product was elaborated to the corresponding bicyclic nucleoside as well as an unexpected tricyclic nucleoside.

Mechanism of a gas-phase dissociation reaction of 4-aminobutyl glycosides under CID MS/MS conditions

The assembly of monosaccharides during the synthetic process of glycan structures is responsible for the diversity of this family of molecules. Because of the complexity of the glycan structure, synthesis of oligosaccharides and structural analysis have been difficult tasks. During efforts to develop glycosides carrying an aglycon that can be used in both functional and structural investigations, we found that 4-aminobutyl glycosides fulfill these criteria. We also observed that the glycosidic linkage underwent an interesting dissociation reaction under collision-induced MS/MS, and that the reaction product is very useful in structural investigation based on mass spectrometry, especially since it provides information regarding anomeric configurations. Despite its importance, the reaction mechanism of the dissociation is not fully understood. For this reason, we studied the mechanism by synthesizing possible products and used them in detailed analyses based on energy-resolved mass spectrometry where the energy dependence of the dissociation reaction was analyzed under collision-induced dissociation conditions. As a result of spectral match with one of synthesized reference compounds, it was suggested that the dissociation reaction to generate a C-ion species and a pyrrolidine took place through a five-membered transition state in two-step reaction sequence.

Highly efficient and stereoselective synthesis of β-glycolipids

beta-Galactosylceramide and glycolipid analogues were prepared in high yield and with complete chemo and stereoselectivity by reaction of alpha-iodo glycosides with stannyl ceramides, formed in situ. TBAI was used to activate both the iodogalactose and the stannyl ether.

Iminosugar thioglycosides as glycosyl donors: a route to disaccharides with an iminosugar moiety

The iminosugar thioglycosides are used as glycosyl donors in glycosidation reactions. Thereby, iminosugar glycosides and disaccharide analogues with an iminosugar moiety are prepared. The yields are high and the method is stereoselective.

Additive Pummerer reaction of 3,5-O-(di-t-butylsilylene)-4-thio-furanoid glycal and stereoselective synthesis of _ -anomer of 4'-thioribonucleosides

Upon reacting 3,5-O-(di-t-butylsilylene) (DTBS)-4-thiofuranoid glycal S-oxide (7) with Ac2O in the presence of TMSOAc and BF3.OEt2, additive Pummerer reaction proceeded to furnish 1,2-di-O-acetyl-3,5-O-DTBS-4-thioribofuranose (8) in 61% yield. When 8 was reacted with bis-O-TMS-uracil and TMSOTf, 2'-O-acetyl-3',5'-O-DTBS-4'-thiouridine (13a) was obtained along with it's beta-anomer (13b) in 93% yield (13a/13b = 22/1). This highly stereoselective glycosidation reaction was applicable to the synthesis of 14-17. The glycosyl donor 8 was also useful for the synthesis of 4'-thio-C-nucleoside 18 and 19. In contrast to the above results, treatment of 8 with TMSCN gave rise to the formation of the spiro derivative 20. To avoid this intramolecular cyclization, 2-O-TBDMS-protected 21 was prepared from 8. Bromination of 21 with TMSBr and substitution reaction of the resulting bromide 22 with Hg(CN)2 gave 1'-C-cyanide 23.

Ionic Liquid [bmim]PF6‐Mediated Synthesis of 1,2‐Orthoesters of Carbohydrates and the Glycosidation Reactions of 4‐Pentenyl Orthoesters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Ionic Liquid [bmim]PF6-Mediated Synthesis of 1,2-Orthoesters of Carbohydrates and the Glycosidation Reactions of 4-Pentenyl Orthoesters

Abstract A facile synthesis of the 1,2-orthoesters of carbohydrates in the ionic liquid [bmim]PF6 without a quaternary ammonium salt like tetrabutylammonium iodide, is described. The glycosidation reactions of 4-pentenyl orthoesters (NPOEs) with different alcohols are also discussed. The work described in this paper showed that [bmim]PF6 is an efficient and recyclable solvent for the synthesis and glycosidation reaction of orthoesters.

The synthesis of cyclic imidates from amides of glucuronic acid and investigation of glycosidation reactions

The synthesis of novel cyclic glycosyl imidates and an investigation of their potential as donors in glycosidation reactions is described. The results show that 1,2-cis glycosides obtained from the reactions of glycosyl acetates or cyclic imidates, each derived from amides of glucuronic acid, result from the anomerisation of initially formed 1,2-trans glycosides.

Modification and characterization of poly(ethylene‐co‐vinyl alcohol) by glycosidation reaction

AbstractPoly(ethylene‐co‐vinyl alcohol) was modified by the covalent bonding of a glucose ester via acetal formation of a surface hydroxyl group using acid as the catalyst. Grafted copolymers were characterized by 1H‐NMR, Fourier transform IR spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:227–232, 2006

Synthesis and Reactions of Glycosides

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access the actual ChemInform Abstract, please click on HTML or PDF.

Regio- and stereocontrolled synthesis and conformational analysis of benzimidazole nucleosides

Regio- and stereocontrolled synthesis and conformational analysis of a series of benzimidazole nucleosides were achieved. A simple method by 1H NMR 1D NOE experiment was developed for estimation of syn or anti conformation of benzimidazole nucleosides. Substituents at C2 of benzimidazole demonstrated to play a key role both in the unexpected regioselectivity of the glycosidic reaction and in the conformation distributions of the final products.

Relevance of the Glycosyl Donor to the Regioselectivity of Glycosidation of Primary‐Secondary Diol Acceptors and Application of These Ideas to in situ Three‐Component Double Differential Glycosidation.

Three pairs of primary-secondary diol acceptors have been exposed to armed, disarmed, and n-pentenyl ortho ester glycosyl donors in glycosidation reactions. It is shown that the regioselectivity of those glycosylations is greatly influenced by the armed, disarmed, or ortho ester nature of the glycosyl donors. The selectivities observed have been used to devise efficient in situ three-component glycosylations involving two donors and one acceptor.

ピラノース環酸素を硫黄原子で置換したチオオリゴサッカリドの合成研究

This paper describes the synthetic studies of sulfur substituted oligosaccharides performed in our laboratory. Efficient and α-selective glycosidation reactions with 5-thiopyranoses were realized employing 1-O-trichloroacetimidates of 5-thiopyranoses carrying 2-OΟ-etheral protective groups. These conditions were applied for the synthesis of sulfur substituted maltose and isothiomaltose derivatives. The Pummerer rearrangement of 2, 3-O-isopropylidene protected 1-dehydrothiopyranose oxide was found to proceed at the C 1 position regioselectively to provide 5-thiopyranose derivative. Experiments employing labeled compound revealed the reaction mechanism. Development of 3-cyano-3-tert-butyldimethylsilyl-propyl (CSP group) thioether brought us an successful synthesis of sulfur substituted galacturonic acid. Enzymatic properties of these analogue against endo-glycosidases are also described.

Relevance of the Glycosyl Donor to the Regioselectivity of Glycosidation of Primary-Secondary Diol Acceptors and Application of These Ideas to in Situ Three-Component Double Differential Glycosidation

[reaction: see text] Three pairs of primary-secondary diol acceptors have been exposed to armed, disarmed, and n-pentenyl ortho ester glycosyl donors in glycosidation reactions. It is shown that the regioselectivity of those glycosylations is greatly influenced by the armed, disarmed, or ortho ester nature of the glycosyl donors. The selectivities observed have been used to devise efficient in situ three-component glycosylations involving two donors and one acceptor.

Synthesis of Glycoconjugate Vaccines for Candida albicans Using Novel Linker Methodology

[reaction: see text] The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain that contains predominantly alpha-linked mannose residues. However, it is the minor beta-mannan component of the phosphomannan of clinically important Candida strains that provides immunological protection in animal models of fungal disease and hence holds promise as a component of conjugate vaccines. This important antigen occurs in different forms linked to the alpha-mannan backbone via a phosphodiester bond (acid-labile beta-mannan) or directly via a glycosidic bond. To reproducibly synthesize and evaluate conjugate vaccines, a robust method for the synthesis of the different oligosaccharide epitopes is required. Here, we report the gram-scale syntheses of both types of epitopes by an approach that utilizes glucosyl trichloroacetimidate donor 2 to first create a beta-glucopyranoside linkage and then epimerizes the C-2 center via an oxidation-reduction sequence that provides an efficient multigram scale route to the beta-mannopyranosides 5, 8, and 15. Reaction of glycosides 16-18 with homobifunctional adipic acid p-nitrophenyl diesters in dry DMF gave the corresponding half esters in good yields, and of sufficient stability to permit chromatographic purification. Subsequent conjugation with BSA and tetanus toxiod (TT) under mild conjugation conditions afforded the corresponding tri- and tetrasaccharide neoglycoproteins with good efficiency. The conjugation method is also applicable to the coupling of small amounts (mg) of larger oligosaccharides with different proteins.

Immunomodulatory α‐Galactoglycosphingolipids: Synthesis of 2'‐Fluoro‐2'‐deoxy‐α‐galactosylceramide and an Evaluation of Its Immunostimulating Properties

AbstractIn the framework of a project to assess the immunomodulating properties of α‐galactosyl glycosphingolipids, the total synthesis of 1‐O‐(2‐fluoro‐2‐deoxy‐α‐D‐galactopyranosyl)‐2‐docosanoylamino‐1,3,4‐octadecanetriol (1), a 2'‐fluoro analogue of the immunostimulating α‐galactoglycosphingolipids, was accomplished. The glycosidation reaction of the azido precursor of sphingosine was performed using the Mukaiyama glycosidation reaction. The stimulation of mouse splenocyte proliferation by the 2'‐fluoro analogue was highly reduced compared to that of the α‐galactoglycosphingolipids, thereby confirming that a free galactose 2‐OH group is essential for the immunostimulatory activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)