Glycosylation Of Compounds Research Articles

Chemistry of 1,2-Anhydro Sugars.

The 1,2-anhydro sugars are a class of valuable and versatile intermediates in carbohydrate chemistry. In the first part of this article, a review is given on preparation methods of 1,2-anhydro sugars that are suitably protected. Protected 1,2-anhydro sugars have been widely used as glycosyl donors for the synthesis of glycosyl compounds such as oligosaccharides and nucleosides. In the second part, a brief history and the chemistry of unprotected 1,2-anhydro sugars is described. In the past few years, our research group has developed protection-free methods for synthesis of glycosyl compounds through unprotected 1,2-anhydro sugars as reactive intermediates based on the concept of 'direct anomeric activation'. In this article, the one-step preparation of glycosyl compounds such as thioglycoside derivatives and glycosyl azides by using formamidinium-type dehydrating agents is presented. Furthermore, the initial results on the first detection of unprotected 1,2-anhydro sugar intermediates by NMR measurements are shown along with their full structure characterizations.

Glycosyl Bunte Salts: A Class of Intermediates for Sugar Chemistry.

S-Glycosyl thiosulfates have been discovered as a new class of synthetic intermediates in sugar chemistry, named "glycosyl Bunte salts" after 19th-century German chemist, Hans Bunte. The synthesis was achieved by direct condensation of unprotected sugars and sodium thiosulfate using a formamidine-type dehydrating agent in water-acetonitrile mixed solvent. The application of glycosyl Bunte salts is demonstrated with transformation reactions into other glycosyl compounds such as a 1-thio sugar, a glycosyl disulfide, a 1,6-anhydro sugar, and an O-glycoside.

Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates.

The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.

ChemInform Abstract: Palladium‐Catalyzed Glycosylation: Novel Synthetic Approach to Diverse N‐Heterocyclic Glycosides.

AbstractThe developed method allows for the α‐ or β‐selective preparation of a range of N‐heterocyclic glycosyl compounds.

Palladium-catalyzed glycosylation: novel synthetic approach to diverse N-heterocyclic glycosides.

An efficient and highly stereoselective method for the construction of N-heterocyclic glycosides is reported. This method is based on a palladium-catalyzed allylation which proceeded to provide N-heterocyclic glycosyl compounds in good-to-excellent yields with β- or α-selectivity. Various N-nucleophiles were examined for this reaction and selected N-glycosyl isatin substrates were further elaborated to bis-indole sugars which have potential as antiproliferative drugs.

Toward Bis C,C‐Glycosyl Compounds and Anomeric γ‐Glycoamino Acids through Michael Addition Reaction of Nitromethane on Z/E Push‐Pull Sugar Olefins

AbstractThe nucleophilic addition of a nitronate anion on push‐pull anomeric sugar olefins has been studied and the results reveal that this reaction opens a new and efficient access to anomeric γ‐nitro esters when applied to furanoglycosylidenes. The 1,4‐addition reaction occurs mainly from the less‐crowded face, i.e. the opposite side to the 4,5‐isopropylidene protecting group. Very different reactivities for E and Z isomers were observed and this experimental finding was rationalized on the basis of quantum mechanical calculations. Chemical manipulation of the nitro function of these bis C,C‐glycosyl compounds led to a series of new γ‐glycoamino acids, which are chiral building blocks that may be useful for the synthesis of glycopeptides oligomers or scaffolds for the construction of bioactive compounds. Under the same reaction conditions, pyranoglycosylidenes were more prone to migration of the double bond than to the expected 1,4 addition reaction.

Studies on biotransformation of chemical constituents of Tongmai formula by human intestinal flora

To study the chemical constituents in Tongmai formula (TMF) after biotransformation by human intestinal flora (HIF), water extract of TMF was anaerobically incubated with HIF at 37 degrees C. Column chromatographic methods over silica gel, Sephadex LH-20 and semi-preparative high-performance liquid chromatography as well as recrystallization were used to isolate and purify the chemical constituents in TMF after biotransformation by HIF. The chemical structures of isolated compounds were identified on the basis of MS and NMR data. Twenty-six compounds were obtained and identified as phenylpropionic acid (1), 6"-O-acetylpuerarin (2), formononetin(3), daidzein(4), p-hydroxyphenylpropionic acid (5), 3-indolepropionic acid (6), genistein (7), isoformononetin (8), isoononin (9), a mixture of (-)-puerol B-2"-O-glucopyranoside (10a) and (+) -puerol B-2"-O-glucopyranoside (10b), 8-hydroxydaidzein (11), puerol A (12), 3'-methoxy-6"-O-acetylpuerarin (13), 6"-O-acetyldaidzin (14), 3'-methoxydaidzin (15), puerol B (16), 3-methyluracil (17), genistin (18), daidzin (19), 3'-methoxypuerarin (20), mirificin (21), swertiamarin (22) , daidzein-7, 4'-O-glucoside (23), adenine (24), 3'-hydroxypuerarin (25), and puerarin (26). After biotransformation by HIF, the glycosides in TMF were transformed into aglycone and/or less glycosyl compounds along with some hydroxylation and demethylation reactions. Therefore, the glycosides in the TMF are the pro-drug.

Tetrasubstituted C‐Glycosylidenes and C‐Glycosyl Compounds from Di‐ and Monobromo‐Substituted exo‐Glycals

AbstractEfficient methods for functionalization of readily available exo‐glycals have been developed. Sequential palladium‐catalysed cross‐coupling of dibromo‐substituted exo‐glycals was first explored and allowed the formation of new disubstituted exo‐glycals as single stereoisomers. Bromination of furano‐ and pyrano‐methoxycarbonyl‐exo‐glycals led to a new series of monobrominated derivatives. These vinylic bromides were used in carbon‐carbon bond formation through palladium‐catalysed reactions, leading to a new series of previously unknown exo‐glycals. Further chemical manipulation of the methoxycarbonyl functionalities and stereoselective hydrogenation of the exocyclic double bond led to C‐glycosyl compounds with high stereocontrol.

New Amphiphilic Glycopolymers Based on a Polycaprolactone‐maleic anhydride Copolymer Backbone: Characterization by 15N NMR and Application to Colloidal Stabilization of Nanoparticles

Abstract8‐Amino‐3,6‐dioxaoctyl α‐D‐mannopyranoside and 8‐amino‐3,6‐dioxaoctyl β‐D‐galactopyranoside were prepared for coupling with a copolymer made from PCL macromonomers and MA. The new glycosyl compounds as well as PCL macromonomers were synthesized by appropriate techniques and fully characterized. The grafting of the latter with the functionalized copolymer was ascertained by 15N NMR experiments. The glycopolymers thus obtained were used in conjunction with Pluronic® F‐68 for the stabilization of PCL nanoparticles prepared by the emulsification‐diffusion technique. The stabilization of these nanoparticles upon storage and after centrifugation was investigated as well.magnified image

Free-radical and ionic routes towards hydrolytically stable and bioactive C-glycosyl compounds

Photo-initiated addition of glycopyranosyl radicals to such radical acceptors as allyltributyltin, acrylonitrile, or diethyl vinylphosphonate was efficiently achieved to afford stereoselectively α-configured C-glycosyl compounds. With acrylonitrile or diethyl vinylphosphonate, catalytic amounts of organotin were used with NaBH3CN in excess. C-1 Sugar dihalides may be converted into the β-configured C-glycosyl analogues in two radical steps (C–C bond formation, reduction), or into bis-C,C-glycosides (two C–C bond forming reactions in one pot). These dihalides also opened the first access to C-glycodienes. C-Glycosyl-ethylphosphonic acids were elaborated into non-isosteric C-glycosyl mimics of natural sugar nucleotide diphosphates, which were evaluated as inhibitors of glycosyl transferases. In another approach, aromatic electrophilic substitution of 1,4-dimethoxybenzene by d-glycopyranosylium ions gave access to C-glycosyl derivatives of 1,4-dimethoxybenzene hydroquinone, and 1,4-benzoquinone. Some were found to inhibit protein tyrosine phosphatase 1B (PTP1B) and glycogen phosphorylase (GP), as shown by enzymatic and crystallographic studies. Extension of the synthetic work led to C-glycosyl-chromanols and C-glycosyl-tocopherols, which have been studied as anti-oxidants. L'addition photo-initiée de radicaux glycopyranosyl sur des accepteurs de radicaux comme l'allyltributyl étain, l'acrylonitrile, le diéthyl vinylphosphonate procède efficacement pour donner stéréosélectivement les composés α-C-glycosylés correspondants. Avec l'acrylonitrile et le diéthyl vinylphosphonate, l'addition s'obtient en présence de quantités catalytiques d'organo-étain et d'un excès de NaBH3CN. Les C-1 dihalogéno-sucres peuvent conduire aux analogues C-glycosylés de configuration β en deux étapes radicalaires (formation de liaison C–C, réduction), aux bis-C,C-glycosides (création de deux liaisons C–C en un pot), ou à des C-glycodiènes (formation de liaison C–C, élimination). Les acides C-glycosyl-éthylphosphoniques ont mené à des mimes C-glycosylés non isostères de nucléotides sucres diphosphates naturels, qui ont été évalués comme inhibiteurs de glycosyl transférases. L'un d'eux inhibe efficacement (IC50 = 40 μM) la β-1,4-galactosyltransférase du lait de vache (β-1,4-GalT, EC 2.4.1.22). Par ailleurs, la substitution électrophile du1,4-diméthoxybenzène par des ions d-glycopyranosylium donne accès à des dérivés C-glycosylés du1,4-diméthoxybenzène, de la 1,4-benzoquinone et de l'hydroquinone. Certains inhibent modérément la protéine tyrosine phosphatase 1B (PTP1B) ou la glycogène phosphorylase (GP), comme on l'a montré par enzymologie et cristallographie. Les synthèses ont été adaptées pour conduire à des chromanols C-glycosylés ou à des tocophérols C-glycosylés, dont les propriétés antioxydantes ont été étudiées.

Novel 3-O-Glycosyl-3-demethylthiocolchicines as Ligands for Glycine and γ-Aminobutyric Acid Receptors

New 3-O-glycosyl-3-demethylthiocolchicines containing natural and unnatural sugar moieties were prepared and tested on gamma-aminobutyric acid (GABA) and strychnine-sensitive glycine receptors present in rat brain and spinal cord. Two different synthetic approaches were used with the readily available 3-O-demethylthiocolchicine (1b) and thiocolchicoside (2a). Glycosyl compounds 2a-g were obtained from 1b and 1-fluorosugars 4. 6'-Heterosubstituted glycosyl compounds 6-12 and the 6'-desoxy derivative 2h were prepared from 2a.

Negative atmospheric pressure chemical ionisation low-energy collision activation mass spectrometry for the characterisation of flavonoids in extracts of fresh herbs

The flavonoid composition of commonly eaten fresh herbs such as dill, oregano and parsley was analysed by combined LC, MS and low-energy collision induced dissociation (CID) MS–MS. Negative atmospheric pressure chemical ionisation (APCI) MS and MS–MS were used to provide molecular mass information and product-ion spectra of the glycosyl compounds. The most prominent fragment was found to arise from the aglycone ion, which provides molecular mass information about the glycosyl substituent and the aglycone. Product-ion spectra of the aglycone verified the identity by comparison with product-ion spectra of authentic standards. Methoxylated flavonoids provide characteristic fragmentation, i.e., loss of ·CH 3, which add to the usefulness of the method for identifying unknown flavonoids. Negative-mode APCI-MS is thus demonstrated to be a good alternative to the commonly employed positive mode operation.

Reactivity of Halo Sugars on Silver Cathodes

Our extensive research on the reductive electrochemistry of glycosyl derivatives has revealed a remarkable electrocatalytic activity of silver cathodes in the reduction of glycosyl halides, which is strictly related to both the electrode active surface and the reaction medium. The peculiarities exhibited by silver cathodes have been extensively characterised (i) by reactivity studies performed on a wide range of halo sugars by cyclic voltammetry and (ii) by preparative electrolyses leading to the formation of simple and mixed glycosyl dimers and, in the presence of suitable acceptors, of glycosides and glycosyl compounds.

FunctionalizedC-Glycosyl Compounds. III. Reaction of Tertiary Nucleophiles with Unsaturated Carbohydrates. Mechanism of the Anomerization

Abstract Phenyl 2, 3-dideoxy-4, 6-di-O-benzyl-D-erythro-hex-2-enopyranoside 1α (or 1β) is alkylated regio- and stereospecifically at the anomeric center by stabilized tertiary nucleo-philes in the presence of Pd(0) as a catalyst, leading to the C-glycoside of α- (or β-) configuration. The observed loss of stereoselectivity using secondary stabilized nucleophiles is mainly due to a retro Michael reaction. The assignment of the α- (or β-) configuration at the anomeric center was accomplished using 13C NMR and NOE experiments.

ChemInform Abstract: Phospho Sugars. Novel Preparation and Their Glycosyl Compounds.

AbstractThe phospholene 1‐oxides (IV) or (VI) are converted to the phospho sugars (IX) by consecutive bromination, stereoselective oxidation with osmium tetroxide, and peracetylation.

Phospho Sugars; Novel Preparation and Their Glycosyl Compounds

Treatment of 1-phenyl-2-, and -3-phospholene 1-oxides with N-bromosuccinimide affords 4-bromo-1-phenyl-2-phospholene 1-oxide. Substitution of the bromide with acetate, followed by stereoselective oxidation with osmium tetroxide and peracetylation with acetic anhydride/pyridine affords phospho sugar derivatives of tetrafuranose. Furthermore, N-, O-, and S-glycosyl compounds of phospho sugars can be prepared from 3-methyl-1-phenyl-2-phospholene 1-oxide by bromination and nucleophilic substitution reactions. This is a novel and excellent route to prepare phospho sugar derivatives

Glycosyl imidates, 37. Direct O‐glycosylation of compounds containing a PO(OH) moiety

AbstractThe O‐benzylated α and β‐glucosyl trichoroacetimidates 1a–α and 1a–β afforded with the phosphinic acid derivative 2 and the phosphonic acid derivative 3 directly the corresponding O‐glucosylated products 4 and 5, resp., with inversion at the anomeric center. The corresponding O‐acetylated trichloroacetimidates 1b–α and 1b–β provided both the β‐products due to neighboring group participation. With the amidophosphoric acid derivative 6 and the trichloroacetimidate 1b–α the O‐glucosylated compound 8–β was obtained. The O‐acetylated 6‐deoxy‐L‐talopyranosyl donor 12 behaved similarly. With compound 2 the α‐phosphinate 13 was formed. Dibenzyl phosphate gave the α‐phosphate 14; subsequent debenzylation led to the 6‐deoxy‐α‐L‐talopyranosyl phosphate 15.

ChemInform Abstract: Intramolecular C‐Arylation of 2,3,5‐Tri‐O‐benzyl‐ and 2,3,5‐Tri‐O‐(3‐methylbenzyl)pentofuranose Derivatives.

Abstract Upon treatment with tin(IV) chloride, 1- O -acetyl-2,3,5-tri- O -benzyl- and 1- O -acetyl-2,3,5-tri- O -(3-methylbenzyl)pentofuranose ( d - ribo , l - arabino ) undergo intramolecular Friedel—Crafts alkylation of the aromatic substituent at O-2 to give unusual internal C -glycosyl compounds (isochroman derivatives) in high yield. The final products are also partially debenzylated at O-3 or O-5 (up to 25%) under these conditions. By contrast, the corresponding methyl glycosides are poor substrates for the intramolecular C -arylation reaction, as methyl 2,3,5-tri- O -(3-methylbenzyl)-β- d -ribofuranoside was found to give preponderantly methyl 3,5-di- O -(3-methylbenzyl)-α- d -ribofuranoside ( 11 ) (49%), and the C -arylation product in 30% yield only in the presence of the same Lewis acid. The competitive formation of 11 is thought to be due to the anomerization of the substrate leading to a tin(IV) complex coordinated with O-1 and O-2, which promoted the cleavage of the benzyl group at O-2. These reactions provide a novel and efficient C -arylation method and suggest a new approach to selectively protected d -ribofuranose derivatives. Evidence for the uncommon C -arylated structure of the new products was gained from their 1 H- and 13 C(APT)-n.m.r. spectra.

ChemInform Abstract: Synthesis of C‐Glycosyl Compounds by the Addition of Glycosyl Radicals to Olefins.

Abstract The Bu3SnH - AIBN induced radical additions of 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl derivatives, bearing α-Br (1), α-I (5) β-OCSSMe (7), and β-SePh (8) groups on the anomeric carbon, with olefins such as dimethyl maleate, methyl vinyl ketone, dimethyl acetylenedicarboxylate, butyl vinyl ether, and N -ethylmaleimide were examined for a synthesis of C -glycosyl compounds.

Total synthesis of cyclomaltohexaose

Described for the first time is a total synthesis of cyclomalthoexaose, in 0.3% overall yield, in 21 steps starting from maltose. Maltose was transformed into allyl O-(2,3,6-tri- O-benzyl-α- d-glucopyranosyl)-(1→4)-2,3,6-tri- O-benzyl-β- d-glucopyranoside ( 5) and O-(4- O-acetyl-2,3,6-tri- O-benzyl-α- d-glucopyranosyl)-(1→4)-2,3,6-tri- O-benzyl-β- d-glucopyranosyl fluoride ( 6). Glycosylation of compound 5 with compound 6, and partial deprotection of the product gave allyl O-(2,3,6-tri- O-benzyl-α- d-glucopyranosyl)-(1→4)-bis[ O-(2,3,6-tri- O-benzyl-ga- d-glucopyranosyl)-(1→4)]-2,3,6-tri- O- benzyl-β- d-glucopyranoside, which was further glycosylated with the glycosyl donor 6, and converted into the key intermediate O-(2,3,6,-tri- O-benzyl-α- d-glucopyranosyl)-(1→4)-tetrakis[ O-(2,3,6,-tri- O-benzyl-α- d-glucopyranosyl)-(1→4)]-2,3,6,- tri- O-benzyl-β- d-glucopyranosyl fluoride 3. The crucial cyclization was achieved through intramolecular glycosylation of the key intermediate 3, to afford a 21% yield of octadeca- O-benzylcyclomaltohexaose ( 2). Catalytic transfer hydrogenation of compound 2 yielded cyclomaltohexaose.