Glycosyl Acetates Research Articles

A Metal-Free β-Stereoselective Synthesis of 2-Deoxy-C-arylglycosides: Synthesis of 5-Aza Analogues of Aquayamycin

AbstractA convenient protocol for the β-stereoselective synthesis of 2-deoxy-C-arylglycosides has been developed. This reaction takes place in one step by using I2/Et3SiH to activate a glycosyl acetate to generate a glycosyl iodide intermediate in situ, which is captured by a naphthol; this is followed by a Fries-like O-to-C glycoside rearrangement to afford a β-C-aryl glycoside selectively. The approach is applicable to a wide range of naphthol moieties, and its utility was demonstrated in syntheses of 5-aza analogues of aquayamycin.

Synthesis of Glycosyl Azides and Their Applications Using CuAAC Click Chemistry to Generate Bis- and Tris(triazolyl)glycosyl Derivatives

2,3-Unsaturated C-(triazolyl)glycosyl acetates have been synthesized from 3,4,6-tri-O-acetyl-d-glucal using C-glycosylation and click chemistry and were then used in a palladium-catalyzed Tsuji–Trost type allylic azidation reaction to afford the corresponding regioisomeric glucal-azide derivatives. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with these glucal-based allylic azides using CuI as the catalyst, led to the corresponding glucal-based bis(triazole) derivatives. Performing further functional group modification and another click (CuAAC) reaction with each of these bis(triazolyl) glycosyl derivatives afforded tris(triazolyl)glycosyl derivatives. Two libraries of regioisomeric bis(triazole) derivatives and a small library of regioisomeric tris(triazole) derivatives of glucal were then synthesized using different alkynes.

Selective anomeric acetylation of unprotected sugars in water.

High yielding selective acetylation of only the anomeric hydroxyl of unprotected sugars is possible in aqueous solution using 2-chloro-1,3-dimethylimidazolinium chloride (DMC), thioacetic acid, and a suitable base. The reaction, which may be performed on a multi-gram scale, is stereoselective for sugars that possess a hydroxyl group at position-2, exclusively yielding the 1,2-trans products. The use of an iterative reagent addition procedure allows the use of sodium carbonate as the base, avoiding the formation of triethylammonium salts, which may hamper product purification. The glycosyl acetate products may be used as donor substrates for glycosidase-catalysed synthesis. The crude aqueous acetylation reaction mixture may also be used for this purpose.

An Improved Helferich Method for the α/β-Stereoselective Synthesis of 4-Methylumbelliferyl Glycosides for the Detection of Microorganisms.

An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the use of base, the glycosylation reaction proceeds more easily, is uncommonly α- or β-stereoselective, and affords the corresponding products in moderate to excellent yields (51%–94%) under appropriate conditions.

In(III) Triflate-Mediated Solvent-Free Synthesis and Activation of Thioglycosides by Ball Milling and Structural Analysis of Long Chain Alkyl Thioglycosides by TEM and Quantum Chemical Methods

Conventional solution-phase synthesis of thioglycosides from glycosyl acetates and thiols in the presence of In(III) triflate as reported for benzyl thioglucoside failed when applied to the synthesis of phenolic and alkyl thioglycosides. But, it was achieved in high efficiency and diastereospecificity with ease by solvent-free grinding in a ball mill. The acetates in turn were also obtained by the homogenization of free sugars with stoichiometric amounts of acetic anhydride and catalytic In(OTf)3 in the mill as neat products. Per-O-benzylated thioglycosides on grinding with an acceptor sugar in the presence of In(OTf)3 yield the corresponding O-glycosides efficiently. The latter in the case of a difficult secondary alcohol was nearly exclusive (>98%) in 1,2-cis-selectivity. In contrast, the conventional methods for this purpose require use of a coreagent such as NIS along with the Lewis acid to help generate the electrophilic species that actually is responsible for the activation of the thioglycoside donor in situ. The distinctly different self-assembling features of the peracetylated octadecyl 1-thio-α- and β-D-galactopyranosides observed by TEM could be rationalized by molecular modeling.

Tri-isopropylsilyl thioglycosides as masked glycosyl thiol nucleophiles for the synthesis of S-linked glycosides and glyco-conjugates.

Tri-isopropylsilyl thio-glycosides (TIPS S-glycosides) were synthesized through base promoted SN2 substitution of glycosyl halides with TIPS-SH or by Lewis acid promoted glycosylation of TIPS-SH with glycosyl acetates or p-methoxyphenyl glycosides. Various thioglycoside derivatives were obtained in high yields by one-pot fluoride-mediated de-silylation and thiol alkylation with alkyl halides or Michael acceptors of one common TIPS S-glycoside.

Synthesis of Spirolactonic C-Sialosides Induced by Samarium Diiodide

A method for the synthesis of spiro-δ-lactonic α-C-sialosides by samarium diiodide mediated cyclization reactions of glycosyl 2-pyridylsulfides or acetates with appropriate carbonyl side chains has been developed.

Facile TMSOTf-catalyzed preparation of 2-deoxy α-O-aryl-D-glycosides from glycosyl acetates

2-Deoxy α-O-aryl glycosides were conveniently obtained by reaction of 2-deoxy-glycosyl acetates with phenols in the presence of TMSOTf as the promoter. The current method provides the O-aryl glycosides with good to excellent yields, and sole alpha selectivity.

Armed–disarmed effect of remote protecting groups on the glycosylation reaction of 2,3-dideoxyglycosyl donors

The armed–disarmed effect of remote protecting groups at the C-4 and/or C-6 position(s) on the glycosylation reactions of 2,3-dideoxyglycosyl donors was investigated. It was found that under various glycosylation conditions, 4- or 6-O-Bn 2,3-dideoxyglycosyl donors were much more reactive than the corresponding 4,6-di-O-Bz 2,3-dideoxyglycosyl donors. Based on these results, an effective and chemoselective glycosylation reaction using 4,6-di-O-Bn glycosyl acetate and 4-OH-6-O-Bz glycosyl acetate was realized, producing a 2,3-dideoxydisaccharide in good yield with high α-stereoselectivity.

Ultrasound-assisted synthesis of C-glycosides

A significant rate enhancement was observed in the preparation of allyl and allenyl-C-glycosides from glycosyl acetate or methyl O-glycoside precursors when ultrasound irradiation was employed as an energy source. The C-glycosides were obtained in 77–96% yields in <20 min using TMSOTf as promoter. These results show that sonication provides rapid and efficient access to useful C-glycoside-based building blocks.

ChemInform Abstract: Synthesis of Glycosyl Phosphonates and Related Compounds.

The synthesis of glycosylphosphonates, isopolar, nonisosteric analogues of glycosylphosphates, from halonitro ethers, glycosyl acetates, or glycosyl trichloroacetimidates is reviewed. A new approach to phosphonate analogues of myo-inositol trisphosphate (50) is described. Based on a hypothetical reaction mechanism for the formation of thioethers from a glyoxalase I inhibitor, an advanced intermediate 59 for the synthesis of diphosphonate–phosphate analogues of 50 is obtained by an addition–elimination–addition sequence from 54. Finally, glucosylphosphines, characterized as the corresponding phosphine oxides 61 and 62 have been prepared from the glycosylidene diazirine 60, a precursor of the tetra-O-benzylglucopyranosylidene carbene. The phosphine oxides 61 and 62 were also obtained by reaction of the glycosyl acetate 18 with methyl diphenylphosphinite.

Effective and chemoselective glycosylations using 2,3-unsaturated sugars

Glycosyl donors containing a double bond between C2 and C3 were designed by mimicking the reaction mechanism of lysozyme-initiated hydrolysis of mucopolysaccharides. It was found that, under various glycosylation conditions, the reactivities of 2,3-unsaturated glycosyl acetates were significantly higher, while those of the corresponding 2,3-unsaturated-4-keto glycosyl acetates were much lower than those of the corresponding 2,3-dideoxy (2,3-saturated) glycosyl acetates. Based on these results, chemoselective glycosylations were effectively realized via combinatorial techniques in short-steps using three types of glycosyl donors to construct several types of deoxyoligosaccharides. Furthermore, the highly reactive 2,3-unsaturated glycosyl acetates were found to be useful in the synthesis of the O-glycosides of low reactive tertiary alcohols.

Chemoselective glycosylations using 2,3-unsaturated-4-keto glycosyl donors

2,3-Unsaturated-4-keto glycosyl acetates were found to exhibit low reactivity under several glycosylation conditions. Chemoselective glycosylations were effectively performed using 2,3-unsaturated glycosyl and 2,3-dideoxy glycosyl acetates as armed glycosyl donors, and 2,3-unsaturated-4-keto glycosyl acetates as disarmed glycosyl donors.

Synthesis of β- C-glycopyranosyl-1,4-naphthoquinone derivatives and their cytotoxic activity

β- C-Glucosyl and β- C-galactosyl-1,4-dimethoxynaphthalenes have been synthesized using a F 3CCO 2Ag/SnCl 4 promoted Friedel–Crafts electrophilic substitution reaction. Both glycosyl acetates and methyl glycosides can be used as glycosyl donors. Further oxidation afforded the corresponding β- C-glycosyl-1,4-naphthoquinones. The in vitro cytotoxic activity of these compounds was evaluated against the A375 cell line.

Toward the total synthesis of vineomycin B 2: application of an efficient glycosylation methodology using 2,3-unsaturated sugars

The application of an efficient glycosylation methodology using 2,3-unsaturated sugars to synthesize critical precursors required for the total synthesis of an antibiotic, vineomycin B 2 ( 1), was demonstrated. The required disaccharide, the acurosyl rhodinose derivative of 1, was prepared by chemoselective glycosylation using a 2,3-saturated glycosyl acetate corresponding to the rhodinose moiety and a 2,3-unsaturated glycosyl acetate corresponding to the acurose portion. Further, the right-hand side chain of 1, consisting of β-oxo- tert-alcohol and rhodinose, was constructed by a powerful glycosylation approach using a 2,3-unsaturated glycosyl acetate in an ionic liquid under reduced pressure.

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.

Sonochemistry: A Powerful Way of Enhancing the Efficiency of Carbohydrate Synthesis

Using sonication as a means of facilitating organic reactions in carbohydrate chemistry was explored under the conditions used for traditional organic synthesis. An array of representative reactions, including hydroxy group manipulation (acylation, protection/deprotection, acyl group migration), thioglycoside synthesis, azidoglycoside synthesis, 1,3-dipolar cycloaddition and reductive cleavage of benzylidene, commonly used in the synthesis of carbohydrate derivatives was examined. A series of glycosylation reactions that employ thioglycosides, glycosyl trichloroacetimidate, glycosyl bromide and glycosyl acetate as the glycosyl donors was also examined. Our results demonstrate that sonication can significantly shorten the reaction time, enhance the reactivity of reactant and lead to superior yield and excellent stereoselectivity. More importantly, a general protocol of glycosylation may finally be developed. Sonication is compatible to the conditions used for traditional organic synthesis. We believe that sonication can also be applied to other areas of synthetic processes.

イッテルビウム(III)トリフラートを活性化剤に用いるグリコシルアセテートの高立体選択的グリコシル化法の開発

イッテルビウム(III)トリフラートを活性化剤に用いるグリコシルアセテートの高立体選択的グリコシル化法の開発

Glycosyl Phosphonium Halide as a Reactive Intermediate in Highly α‐Selective Glycosylation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of a glycolipid for studying mechanisms of mitochondrial uncoupling proteins

Glucose- O-ω-palmitic acid is an amphipathic molecule that is useful as a tool for studying the mechanism of mitochondrial uncoupling proteins. The synthesis of this glycolipid is described herein. The study of the reaction of a series of glycosyl donors with appropriate acceptors derived from 16-hydroxyhexadecanoic acid showed that a glycosyl trichloroacetimidate donor was more efficient than thioglycoside, glycosyl halide and glycosyl acetate donors for synthesis of this glycolipid.