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Condensation between unprotected aldoses and dibenzoylmethane catalyzed by NaHCO3 in the cosolvents EtOH and H2O (4:1) under microwave irradiation gave aryl ketone β-C-glycosides 6b–i in higher yields (from 50% with C-riboside 6g up to 99% with C-glucoside 6b) and better anomeric selectivities (β-configuration >95%) in a shorter reaction time (90 min), compared with previous conventional methodologies. This method provides an attractive alternative to the existing means for the preparation of high value ketone β-C-glycosides.

Synthesis of a series of novel (6-deoxy-glycopyranosid-6-yl) sulfone derivatives has been achieved using a general synthetic strategy. Yields were excellent in every case. The synthetic compounds were evaluated for their biological potential against Ca 2+ -ATPase, an important enzyme involves in tranporting Ca 2+ across the cell membranes.

We have explored the preparation of conformationally-restricted pseudonucleosides bearing a spiranic thiohydantoin scaffold on C-3 of the sugar moiety by coupling partially protected 3-amino-3-methoxycarbonyl and 3-isothiocyanato-3-methoxycarbonyl glucofuranose derivatives with alkyl(aryl)isothiocyanates or with alkyl(aryl)amines; the key step is a spontaneous or thermal-induced intramolecular nucleophilic substitution of transient thioureas. Upon deprotection, final spiranic thiohydantoins were evaluated as glycosidase and glycogen phosphorylase inhibitors.

Four conformationally constrained fused oxa-aza spiro sugars have been synthesized from perbenzylated D-glucono-lactone involving C-glycosylation of ketoses by using Me 3 -SiCN, ring-closing metathesis, and diastereoselective dihydroxylation as key steps. Two of the four spiro sugars were found to be highly selective but moderate inhibitors of α-mannosidase.

N-Methylation of syn- or anti-configured 3,6-dihydro-2H-1,2-oxazines and subsequent treatment with triethylamine smoothly provided enantiopure α,β-unsaturated β-alkoxy-γ-amino aldehydes bearing different protected diol, triol, or tetrol side chains in good to excellent yields. The N-0 bond cleavage occurs under mild conditions and involves an internal redox process. The method is also applicable to tetrahydro-2H-1,2-oxazines, which either lead to 4-amino ketose or aldose derivatives (D-sorbose or D-idose configuration). The equivalency of the generated β-alkoxyenal moiety with 1,3-dicarbonyl compounds could be demonstrated by condensation reactions with hydrazine or 2-aminoimidazole derivatives providing a series of new pyrazole or imidazo[ 1,2-a]pyrimidine derivatives with stereodefined and protected aminopolyol side chains.

A new 2-oxazolines containing S-galactosyl substituents linked to alkyl chains of different lengths; (S-glycooxazoline) were prepared relatively in high yields. By using a 1:1 adduct of 2-methyl-2-oxazoline and methyl triflate, as the initiator, the monomer was polymerized via ring-opening polymerization (ROP) to give products with relatively narrow molecular weight distributions. Homo- and copolymerization were performed, and the kinetics of these new S-glycooxazolines in the ROP are investigated. After a quantitative deprotection, poly(2-oxazoline)s having pendant carbohydrate were obtained. The interaction of the poly(S-glycooxazoline) with RCA120 lectin was investigated, the binding constant between glycopolymer and lectin was increased by 102 times compared with that of the monosaccharide (D-galactose). The in vivo expression of green fluorescent protein using the synthesized poly(S-glycooxazoline)s as polymeric inducers in Escherichia coli host were performed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

This study focuses on the preparation of some 1-alkynyl-2-deoxy- d -riboses and their application to the generation of C-nucleosides analogues. Examples are provided in which the alkyne functionality took part in alkylation or cycloaddition reactions. A discussion of the protecting group used is provided.

A highly regioselective one-pot transformation of 2-azido-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-d-glucopyranose via sequential additions of various reagents was systematically studied, yielding the fully protected derivatives and the 1-, 3-, 4-, as well as 6-alcohols, respectively.

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d -(−)-ribose and ethyl ( S )-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels–Alder reaction.

A branched-chain aldose bearing an azido group at the C-2 position provides access to the corresponding 1-deoxy-1-azido- and 1-deoxy-1-amino ketoses in a single step via stereospecific isomerization. The isomerization exploited the catalytic effect of molybdate ions and microwave irradiation. The structures of the products were analyzed by NMR spectroscopy, IR, HRMS spectrometry and quantum-chemical DFT calculations. DFT-computed proton-proton coupling constants of the prepared Amadori ketose 1-deoxy-1-amino- d - gluco -heptulose were found to be comparable with the experimentally obtained coupling constants and were in agreement with the 4 C 1 pyranose form in aqueous solution at room temperature.

Solution densities and speeds of sound of tripeptide (gly(gly)2) in aqueous and aqueous glucose solutions have been determined at temperatures: 288.15, 293.15, 298.15, 303.15 and 308.15 K. These solution densities and speeds of sound were used to calculate apparent molar volume at infinite dilution ( V ϕ 0 ) transfer partial molar volume ( Δ t r V ϕ 0 ) apparent molar adiabatic compressibility at infinite dilution ( K ϕ , S 0 ) , and its transfer values ( Δ t r K ϕ , S 0 ) , at infinite dilution. These parameters have been discussed in terms of solute–solvent interactions. We have also attempted to examine the temperature and concentration dependence of such interactions. Contributions of peptide group (–CONH–) to V ϕ 0 and K ϕ , S 0 in aqueous solution at 298.15 K are also estimated by comparing with the data in the literature and of α,ω-amino acids. Also group contributions to transfer volumes at temperatures: 288.15, 298.15 and 308.15 K from water to aqueous glucose solutions have also calculated.

We report a novel approach to the synthesis of GlcNAcstatins—members of an emerging family of potent and selective inhibitors of peptidyl O-GlcNAc hydrolase build upon tetrahydroimidazo[1,2-a]pyridine scaffold. Making use of a streamlined synthetic sequence featuring de novo synthesis of imidazoles from glyoxal, ammonia and aldehydes, a properly functionalised linear GlcNAcstatin precursor has been efficiently prepared starting from methyl 3,4-O-(2′,3′-dimethoxybutane-2′,3′-diyl)-α-d-mannopyranoside. Subsequent ring closure of the linear precursor in an intramolecular SN2 process furnished the key fused d-mannose-imidazole GlcNAcstatin precursor in excellent yield. Finally, a sequence of transformations of this key intermediate granted expeditious access to a variety of the target compounds bearing a C(2)-phenethyl group and a range of N(8) acyl substituents. The versatility of the new approach stems from an appropriate choice of a set of acid labile permanent protecting groups on the monosaccharide starting material. Application was demonstrated by the synthesis of GlcNAcstatins containing polyunsaturated and thiol-containing amido substituents., Graphical abstract

Aims: Characterization of substrate specificity of a d-lyxose isomerase from Serratia proteamaculans and application of the enzyme in the production of d-lyxose and d-mannose. Methods and Results: The concentrations of monosaccharides were determined using a Bio-LC system. The activity of the recombinant protein from Ser. proteamaculans was the highest for d-lyxose among aldoses, indicating that it is a d-lyxose isomerase. The native recombinant enzyme existed as a 54-kDa dimer, and the maximal activity for d-lyxose isomerization was observed at pH 7·5 and 40°C in the presence of 1 mmol l−1 Mn2+. The Km values for d-lyxose, d-mannose, d-xylulose, and d-fructose were 13·3, 32·2, 3·83, and 19·4 mmol l−1, respectively. In 2 ml of reaction volume at pH 7·5 and 35°C, d-lyxose was produced at 35% (w/v) from 50% (w/v) d-xylulose by the d-lyxose isomerase in 3 h, while d-mannose were produced at 10% (w/v) from 50% (w/v) d-fructose in 5 h. Conclusions: We identified the putative sugar isomerase from Ser. proteamaculans as a d-lyxose isomerase. The enzyme exhibited isomerization activity for aldose substrates with the C2 and C3 hydroxyl groups in the left-hand configuration. High production rates of d-lyxose and d-mannose by the enzyme were obtained. Significance and Impact of the Study: A new d-lyxose isomerase was found, and this enzyme had higher activity for d-lyxose and d-mannose than previously reported enzymes. Thus, the enzyme can be applied in industrial production of d-lyxose and d-mannose.

Readily available tetrabutylammonium bromide (TBAB, 10 mol%), in the molten state, efficiently catalyzes the reaction of a variety of in situ generated enamines, from arylamines and 1,3-ketones, with aldose sugars under solvent-free conditions. The reaction proceeds rapidly and affords the corresponding protected annulated pyrrole derivatives in good to high yields (55-78%) after acetylation. The present methodology offers advantages such as excellent yields, a simple procedure, shorter reaction times, and milder conditions.

Apparent molar volumes (ϕV) and viscosity B-coefficients for some carbohydrates (d-glucose, d-mannitol, and d-sucrose) in (0.001, 0.003, and 0.005) mol·kg−1 aqueous cetrimonium bromide (N-cetyl-N,N,N-trimethyl ammonium bromide) (C19H42BrN) solutions have been determined from solution density, ρ, and viscosity, η, measurements at (298.15, 308.15, and 318.15) K as a function of the concentration of carbohydrates. The limiting apparent molar volume (ϕV0) and experimental slopes (Sv*) obtained from the Masson equation have been interpreted in terms of solute−solvent and solute−solute interactions, respectively. The viscosity data were analyzed using the Jones−Dole equation, and the derived parameters A and B have also been interpreted in terms of solute−solute and solute−solvent interactions, respectively, in the mixed solutions. The structure-making or -breaking ability of carbohydrates has been discussed in terms of the sign of (δ2φV0/δT2)P as well as dB/dT. The three-dimensional representation of the inves...

Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many potential applications. Previously, wehave found that certain esters and carbamatesof 4,6-O-benzylidene- a-D-methyl-glucopyranosidearelowmolecularweightgelatorsforavarietyofsolvents,includingwater.In orderto obtain effectiveand robust sugar-based organogelatorsand understand the structure and gelation relationship, we extended our studies using 4,6-O-benzylidene-a-D-methyl-2-deoxy-2-amino-glucopyr- anoside as the headgroup. A series of amides and ureas were prepared from the protected D-glucosamine andthecorresponding isocyanatesoracidchlorides,ingoodyields.Theself-assemblingpropertiesofthese compounds were studied in several solvents, including water and aqueous solutions. Comparing to the ester and carbamate derivatives previously prepared from D-glucose, the amides and urea derivatives afforded more robust gels at lower concentrations typically. Most of these compounds were found to be efficient low molecular weight hydrogelators (LMHGs) for aqueous solutions at concentrations lower than 0.5 wt %. The preparation and characterization of these compounds are reported here. 2010 Published by Elsevier Ltd.

A new strategy for the stereoselective synthesis of 2-amino-2-deoxy-aldoses is described. Therefore epoxy carbamates are reacted with isocyanates to furnish urethanes, which will form the title compounds with high diastereoselectivities under basic conditions and O,O-migration of the carbamoyl group.

The specific activity and catalytic efficiency (k(cat)/K(m)) of the recombinant putative protein from Providencia stuartii was the highest for D-lyxose among the aldose substrates, indicating that it is a D-lyxose isomerase. Gel filtration analysis suggested that the native enzyme is a dimer with a molecular mass of 44 kDa. The maximal activity for D-lyxose isomerization was observed at pH 7.5 and 45 degrees C in the presence of 1 mM Mn(2+). The enzyme exhibited high isomerization activity for aldose substrates with the C2 and C3 hydroxyl groups in the left-hand configuration, such as D-lyxose, D-mannose, L-ribose, D-talose, and L-allose (listed in decreasing order of activity). The enzyme exhibited the highest activity for D-xylulose among all pentoses and hexoses. Thus, D-lyxose was produced at 288 g/l from 500 g/l D-xylulose by D-lyxose isomerase at pH 7.5 and 45 degrees C for 2 h, with a conversion yield of 58% and a volumetric productivity of 144 g l(-1) h(-1). The observed k(cat)/K(m) (920 mM(-1) s(-1)) of P. stuartiid-lyxose isomerase for D-xylulose is higher than any of the k(cat)/K(m) values previously reported for sugar and sugar phosphate isomerases with monosaccharide substrates. These results suggest that the enzyme will be useful as an industrial producer of D-lyxose.

A formal and improved synthesis of natural (+)-varitriol from d -glucose and dimethyl l -tartrate, respectively, are reported. The key steps are the Pd(II)/Cu(II)-catalysed bicyclisation of O-benzyl protected triols l -xylo-15 and l -xylo-15/ l -lyxo-15, respectively, followed by ring opening of intermediate dianhydro- l -gulitol 16. The syntheses of key intermediate of the furanoside portion 17 proceed in 13 steps with 5% (from bisacetone- d -glucose), and in 12 steps with 7.6% over-all yield from dimethyl l -tartrate, respectively.

Glyco-particles bearing glucose units have been prepared via a one-step controlled/living ab initio cross-linking emulsion polymerization of styrene based on self-assembly via a glucose RAFTstab (reversible addition−fragmentation chain transfer colloidal stabilizer). The RAFTstab was synthesized from the monomer 2-(methacrylamido)glucopyranose (MAG) and the hydrophobic trithiocarbonate RAFT agent S-methoxycarbonylphenylmethyl dodecyltrithiocarbonate (MCPDT). In order to obtain glyco-particles stable for biomedical applications, a degradable bis(2-acryloyloxyethyl) disulfide cross-linker (disulfide diacrylate, DSDA) was employed in the emulsion polymerization. The cross-linked glyco-particles were stable in N,N-dimethylacetamide (DMAc), in contrast to the corresponding non-cross-linked glyco-particles which disintegrate to form linear glycopolymers in solution. The cross-linked particles underwent reductive degradation into the constituent linear (primary) chains upon treatment with 1,4-dithiothreitol (DDT...

A synthetic strategy has been developed for the preparation of new globular carbosilane dendrimers with mannose groups at the periphery. It consists of hydrosilylation reaction of allyl tetraacetylmannose with carbosilane dendrimers containing monohydrosilane end groups and the subsequent deacetylation reaction. Evaluation of dendrimer toxicities in dendritic cells by MTT assay were carried out, and evidence a good biocompatibility.

The syntheses of three new diamide-linked γ-cyclodextrin dimers joined by substitution at either a glucopyranose C6 A or C3 A carbon are reported. The syntheses involve the reaction of either C6 A or C3 A amino-substituted γ-cyclodextrin with bis(4-nitrophenyl)succinate to form succinamide linked γ-cyclodextrin dimers or reaction of C6 A azide-substituted γ-cyclodextrin with carbon dioxide to form a urea linked γ-cyclodextrin dimer.

The Baylis–Hillman reaction of 3-O-benzyl-α- d -xylo-pentodialdo-1,4-furanose 2 afforded a diastereomeric mixture of l -ido- and d -gluco-configurated α-methylene-β-hydroxy esters 3a and 3b, respectively, in 1:1 ratio. Conjugate addition of benzyl amine on 3a gave adduct 4a as a major product while, addition of benzyl amine to 3b gave only one diastereomer 4b. Reduction of ester functionality in 4a/4b, opening of 1,2-acetonide functionality followed by reductive amino-cyclization under hydrogenation condition afforded azocanes 1c/1d in good yield.

The application of carbohydrate-derived amino alcohols in the asymmetric arylation of aldehydes by using arylboronic acids as the source of transferable aryl groups is described. The best ligand is derived from the readily available sugar D-xylose and it mediates the addition of a range of arylboronic acids to various aromatic aldehydes in excellent yields and high enantiomeric excesses.

We investigated the hydrothermal conversion of the carbohydrates including glucose, cellulose, and starch to lactic acid using NaOH and Ca(OH)2 as alkaline catalysts. Both catalysts significantly promoted the lactic acid formation. The highest yield of lactic acid from glucose was 27% with 2.5 M NaOH and 20% with 0.32 M Ca(OH)2 at 300°C for 60 s. The lactic acid yields from cellulose and starch were comparable with the yield from glucose with 0.32 M Ca(OH)2 at 300°C, but the reaction time in the case of cellulose was 90 s. The mechanism of lactic acid formation from glucose was discussed by identifying the intermediate products. Lactic acid may be formed via the formation of aldoses of two to four carbons including aldose of three carbons, which are all formed by reverse aldol condensation and double bond rule of hexose. This implies that carbon–carbon cleavage occurs at not only C3C4 but also at C2C3. © 2010 American Institute of Chemical Engineers AIChE J, 2010

The activity of ribose-5-phosphate isomerases (RpiB) from Clostridium difficile for D-ribose isomerization was optimal at pH 7.5 and 40 degrees C, while that from Thermotoga maritima for L-talose isomerization was optimal at pH 8.0 and 70 degrees C. C. difficile RpiB exhibited activity only with aldose substrates possessing hydroxyl groups oriented in the right-handed configuration (Fischer projections) at the C2 and C3 positions, such as D-ribose, D-allose, L-talose, L-lyxose, D-gulose, and L-mannose. In contrast, T. maritima RpiB displayed activity only with aldose substrates possessing hydroxyl groups configured the same direction at the C2, C3, and C4 positions, such as the D- and L-forms of ribose, talose, and allose.

Two bioactive flavonol glucosides, hyperoside and quercitrin, were successfully isolated in one step from the phytochemically unknown medicinal plant Osteomeles schwerinae by high-speed counter-current chromatography using a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (0.5:5.5:1.5:4.5 v/v). From 160 mg of crude extract, 2.1 mg of hyperoside (98.6% purity, 83.3% recovery) and 4.5 mg of quercitrin (99.2% purity, 81.7% recovery) were separated and then their chemical structures were identified by (1)H and (13)C NMR analysis. In addition, the isolates were subjected to an in vitro bioassay to evaluate their inhibitory activity on rat lens aldose reductase. Both quercitrin and hyperoside showed excellent inhibitory activities toward rat lens aldose reductase with the IC(50) values of 0.16 and 4.33 microM, respectively, as compared with positive control, 3,3-tetramethyleneglutaric acid (28.7 microM). So far, chemical constituents and biological activities of O. schwerinae have never been reported. This is the first report on the chemical constituents and biological activity of this plant using semi-preparative high-speed counter-current chromatography separation technique.

We report a new strategy to synthesize densely functionalized highly and hyperbranched glycopolymers. Our methodology combines living radical polymerization and click chemistry. Hyperbranched “clickable” scaffolds synthesized via RAFT polymerization are functionalized with carbohydrate groups using an array of “click” chemistry reactions, namely Cu(I)-catalyzed Huisgen 1,3-cycloaddition of azides and alkynes (CuAAC), thiol−ene addition, and thiol−yne addition. This simple and flexible method yields glycopolymers of unique structures, which are potential candidates for biomedical applications.

Molecular recognition of Glu, Glc 2 -Glc 6 and Mal 3 by a tetrakis(bile acid)―porphyrin conjugate has been studied by using ESI-FTICR mass spectrometry. The bile acid conjugate was observed to form 1:1 noncovalent complexes with saccharides. The conjugate was found to have size-selectivity towards saccharides with three or more glucose residues. The Glc 3 and Glc 4 also formed kinetically the most stable complexes. The electron capture dissociation (ECD) experiments revealed that in complexation of an oligosaccharide three glucose residues interact with the bile acid conjugate, whereas additional glucose residues are susceptible to fragmentation. The ECD results also showed the significance of the porphyrin centre for complexation of an intact oligosaccharide. It is obvious that the complexation of an intact sugar requires at least one bile acid side arm and the porphyrin centre.

In the course of our current studies on the reactivity of alkylidenecarbenes, prepared with the trimethylsilylazide/Bu2SnO method, on conveniently functionalized α-cyanomesylates derived from d -allose, d -arabinose, and d -threose, we have observed the unexpected, but mechanistically interesting formation of enantiomerically β-substituted polyhydroxylated furans. These compounds are the result of a series of cascade fragmentation reactions on unstable intermediates obtained during 1,5C–H insertion reactions from alkylidenecarbenes. The mechanism of the reaction has been investigated by computational methods using DFT analysis.

More than 20 types of carbohydrate epimerase have been reported to date. Distinctly different en- zymes recognize the C1, C2, C3, C4, C5 or C6 position of carbohydrate substrates. They include, for instance, aldose 1-epimerase, N-acetyl-D-glucosamine 2-epimerase, UDP-N-acetylglucosamine 2-epimerase, cellobiose 2- epimerase, D-ribulose-5-phosphate 3-epimerase, L-ribulose-5-phosphate 4-epimerase, UDP-galactose 4- epimerase, dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase, GDP-mannose 3,5-epimerase and ADP-L-glycero-D- mannoheptose 6-epimerase. Their biological properties, catalytic mechanisms and tertiary structures are very diverse. This review focuses on the catalysis, structures and applications of carbohydrate epimerases that have recently been characterized in detail.

The synthesis and testing of configurational stability of chirally monodeuterated PMB- and THP-substituted oxymethyllithiums are described. Macroscopically they are configurationally stable up to −35 °C, the limit of their chemical stability, and microscopically even up to 0 °C. Furthermore, THP-protected oxy-[D1]methyllithium has been applied in the formal synthesis of (6R)-[6-D1]- d -glucose (four steps, 40% yield), an example of its use as a homochiral hydroxymethyl synthon.

The nonproteinogenic amino acids (3S,4S)-L- and (3S,4S)-D-β-hydroxyenduracididine (βhEnd), each containing a cyclic guanidine group and three contiguous stereocenters, have been synthesized for the first time, starting from commercially available diacetone D-glucose. The key inversion reactions for the introduction of the two nitrogen groups at C-2 and C-4 afford products that are diastereomerically pure and easy to purify, thereby allowing the gram-scale preparation of βhEnd derivatives that are suitably protected for peptide coupling reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Two kinds of glucose- and lactose-containing methacrylate-based radiopaque glycopolymers (MGI and MLI) were synthesized and characterized. The first glycopolymer was prepared from 2-(2′,3′,4′,6′-tetra- O -acetyl-β- d -glucosyloxy)ethyl methacrylate (AcGEMA), 2-(2′-iodobenzoyl)-ethyl methacrylate (2-IEMA) and methyl methacrylate (MMA) via bulk radical polymerization, followed by the deacetylation. The second glycopolymer was synthesized directly from 2-lactobionamidoethyl methacrylate (LAMA), 2-IEMA and MMA via radical polymerization in DMSO. The cleavage of the ester bond in 2-IEMA of MGI was determined by 1 H NMR analysis during the deacetylation. The in vitro radiopacity of these glycopolymers was demonstrated with both an X-ray detector and a CT scanner. The in vivo CT-imaging tests performed by intravenous administration of a saline solution containing the selected MLI sample in a mouse model exhibited enhanced visibility of the liver and kidney organs.

The aim of this study was to investigate the effect of various selected solid low-molecular cosolutes ( d -glucose, d -fructose, d -galactose, lactose, saccharose; target concentrations in samples 1% w/w) on viscoelastic properties of model processed cheese (40% w/w dry matter and 50% w/w fat in dry matter) without and with pectin addition (target concentrations in final products: 0.2% w/w and 0.4% w/w, respectively). Dynamic oscillation rheometry with parallel plate geometry was used to evaluate the changes in viscoelastic properties of samples. All applied low-molecular cosolutes (1% w/w) decreased the firmness of processed cheese. The nature of cosolute was not significant, i.e. the firmness of final products was declined by various cosolutes to the similar level regardless of their (i) reducing or non-reducing ability; (ii) structure (mono- or disaccharide, aldose or ketose); or (iii) steric arrangement (comparison of two epimers – d -glucose and d -galactose). The reduction of sample rigidity due to cosolute addition was observed in both cases, i.e. in processed cheese without and also with pectin.

From readily available di-O-isopropylidene-D-glucose, a D-ribofuranoid glycoaminoxy acid and its tBu ester have been efficiently prepared as a new family of sugar building blocks by introducing the phthalimido aminoxy group by a Mitsunobu reaction. We found that the tBu ester can be selectively deprotected with 13.7 % TFA in CH2Cl2 at 0 °C in the presence of the 1,2-O-isopropylidene acetal. This selective deprotection has made possible the synthesis of homo-oligomers of glycoaminoxy acids (up to six sugar units) as a novel type of oligosaccharide mimetics. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

This review summarizes recent approaches towards the selective formation of anomeric aldose and aldulosonic acid phosphates of biological relevance, in particular as precursors for the synthesis of nucleotide-activated sugars.

A series of 4-functionalized phenyl-O-β- d -glycosides were designed, synthesized and evaluated as a new class of mushroom tyrosinase inhibitors. The results demonstrated that compounds 6a–13a bearing a thiosemicarbazide moiety exhibited potent activities with IC50 values range from 0.31 to 52.8 μM. Particularly, compound 9a containing acetylated glucose moiety was found to be the most active molecule with an IC50 value of 0.31 μM. SARs analysis suggested that (1) the thiosemicarbazide moiety remarkably contributed to the increase of inhibitory effects on tyrosinase; (2) the configuration and bond type of sugar moiety also played a very important role in determining their inhibitory activities. The inhibition kinetics and inhibition mechanism study revealed that compound 9a was reversible and competitive type inhibitor, whereas compound 13a was reversible and competitive–uncompetitive mixed-II type inhibitor.

Rare sugars are used for many industrial and medical purposes and are produced by the interconversion between aldoses and ketoses catalyzed by sugar and sugar-phosphate isomerases. Recently, Clostridium thermocellum d-ribose-5-phosphate isomerase (CTRPI), an aldose-ketose isomerase, was cloned in order to synthesize d-allose and its substrate specificity was further characterized for industrial usage. CTRPI has a novel substrate specificity that differs from those of other isomerases, which have broad substrate specificities. CTRPI prefers aldose substrates such as l-talose, d-ribose and d-allose. CTRPI was purified and crystallized in order to determine its three-dimensional structure and thus to elucidate its enzymatic reaction mechanism and understand its substrate specificity. The crystal belonged to the trigonal space group P3(2)21, with unit-cell parameters a = b = 69.5, c = 154.4 angstrom, and diffracted to 1.9 angstrom resolution. According to Matthews coefficient calculations, the crystallographic structure consists of a dimer in the asymmetric unit, with a V(M) of 3.2 angstrom(3) Da(-1) and a solvent content of 61.7%.

A recombinant L-fucose isomerase from Caldicellulosiruptor saccharolyticus was purified as a single 68 kDa band with an activity of 76 U mg(-1). The molecular mass of the native enzyme was 204 kDa as a trimer. The maximum activity for L-fucose isomerization was at pH 7 and 75 degrees C in the presence of 1 mM Mn(2+). Its half-life at 70 degrees C was 6.1 h. For aldose substrates, the enzyme displayed activity in decreasing order for L-fucose, with a k (cat) of 11,910 min(-1) and a K (m) of 140 mM, D-arabinose, D-altrose, and L-galactose. These aldoses were converted to the ketoses L-fuculose, D-ribulose, D-psicose, and L-tagatose, respectively, with 24, 24, 85, 55% conversion yields after 3 h.

An assessment of the relative reactivities of the 4-OH of N-acetylglucosamine acceptors bearing simple protecting groups, beta-linked or alpha-linked D or L sugars at O-3 is presented, using a per-O-acetylated alpha-D-glucosyl trichloroacetimidate donor under activation by BF(3) x OEt(2). The presence of either an acyl or carbonate protecting group at O-3 did not impact the reactivity at O-4 with all glycosylations proceeding successfully. On the other hand, the presence of peracetylated sugars at O-3 of N-acetylglucosamine acceptors did impact the reactivity of the 4-OH. The acceptors with an alpha-D-Man, beta-D-Gal, or beta-D-Glc at O-3 reacted promptly. In comparison, the acceptors bearing a beta-L-Fuc, alpha-L-Fuc, or alpha-L-Rha underwent glucosylation slowly, and unreacted acceptor was recovered from the reaction mixtures. Systematic searches carried out on the disaccharide acceptors and trisaccharide products carrying either a peracetylated beta-D-Gal or beta-L-Fuc at O-3 of the glucosamine residue suggest that, for these two acceptors, a conformational reorientation necessary around the fucosidic linkage contributes to the lower reactivity of the beta-fucosylated acceptor. The acceptors bearing a beta-linked D-Gal, D-Glc, or L-Fuc residue at O-3 each gave trisaccharide products that were mostly stable in the reaction conditions. In contrast, the alpha-linked residues at O-3 were rather unstable in these reaction conditions and the degradation of either the acceptors or trisaccharide products led to low glycosylation yields. In these later reactions, it was impossible to clearly assess which of the acceptor or product underwent degradation as comigration and detection issues prevented us from following these glycosylations by TLC or RP-HPLC. In contrast, the glycosylation of an acceptor carrying an alpha-linked perbenzylated L-Fuc residue at O-3 could be easily monitored by RP-HPLC. The data obtained when monitoring this glycosylation showed that the acceptor underwent prompt glycosylation but a decrease in the absorbance peak corresponding to the trisaccharide along with the appearance of a peak corresponding to a perbenzylated fucose hemiacetal indicated that the trisaccharide product was unstable in the reaction conditions.

An enantioselective synthesis of suitably protected (1R,2S,4S,5S)-4-amino-1-(hydroxymethyl)bicyclo[3.1.0]hexan-2-ol, a key starting material for the synthesis of conformationally locked carbocyclic nucleosides, including the antiviral active North-methanocarbathymidine, is reported. Starting from 2-deoxyribose the target Boc-protected amine was prepared in 33% overall yield under conditions that are ecologically friendlier than previous methods.

A general synthetic approach has been developed for the asymmetric synthesis of chiral δ-lactones and verbalactone using d -glucose. The key intermediate used in this approach was α-diazoketone.

Condensation products of aliphatic aldehydes with 3-sulfanylpropionic acid hydrazide exist in solution as mixtures of linear hydrazone and cyclic 1,3,4-thiadiazepine tautomers. Hydrazones derived from 3-sulfanylpropionic acid hydrazide and aromatic aldehydes and ketones have mostly linear structures of different stereoisomers arising from Z-E isomerism with respect to the double C=N bond and restricted rotation about the C(O)-N bond. Condensation products of 3-sulfanylpropionohydrazide with a series of aldoses give rise to ring-chain-ring tautomeric equilibrium between α,β-isomeric pyranose structures, open-chain aldose hydrazone tautomer, and two diastereoisomeric seven-membered cyclic 1,3,4-thiadiazepine forms.

New copolymers of the vinyl saccharide 2-deoxy-2-methacrylamido-D-glucose (M1) with acrylic and methacrylic (M2) acids differing in composition and molecular mass have been synthesized by free-radical copolymerization. The relative activities of the comonomers are determined. It is found that, for acrylic acid, r 1 = 3.03 ± 0.15 and r 2 = 0.5 ± 0.08 and, for methacrylic acid, r 1 = 1.070 ± 0.1 and r 2 = 1.18 ± 0.13. As is evidenced by potentiometric and viscometric measurements, the vinyl saccharide and acid units are capable of interacting, a circumstance that affects the conformational states of macromolecules.

(13)C-Perlabeled cellulose was obtained in a seven-step approach from (13)C(6)-labeled d-glucose with a cationic ring-opening polymerization as the key step. Isopropylidene protection, benzylation of the remaining free 3-O-position and subsequent deprotection afforded 3-O-benzyl-(13)C(6)-glucose (2). Regioselective bis-pivaloylation followed by subsequent ortho-esterification provided the precursor for the cationic ring-opening polymerization, 3-O-benzyl-(13)C(6)-glucopyranose 1,2,4-orthopivalate (4). The actual polymerization step gave a stereo- and regioregular (13)C-perlabeled (1--4)-beta-glucopyranan derivative, which was deprotected into fully labeled (13)C-cellulose, as the cellulose II allomorph with a DP of 40, in an overall 28% yield. All reaction steps were optimized beforehand with nonlabeled compounds toward high yields and high reproducibility and the final compound was comprehensively analytically characterized.

Addition reactions to a 3,4-anhydroheptanose gave heptanoside analogues of carbohydrate derivatives in good to excellent stereochemical purity. Characterization of the products by (1)H and (13)C NMR, COSY, HSQC-DEPT, HMBC, 1D TOCSY, and NOE experiments were performed to obtain the stereochemistry of addition. The 3,4-anhydroheptanose used in this study is obtained from the ring-expansion of a cyclopropanated galactal and thus demonstrates the synthetic utility of heptanose synthesis via cyclopropanated carbohydrates.

Phase behavior of 1-alkyl-3-methyl imidazolium tetrafluoroborate ([C(n)mim][BF(4)], n = 2 to 10), 6-(hydroxymethyl)oxane-2,3,4,5-tetrol and water has been determined at temperatures in the range of (242.15 to 308.15) K. Binodal Curves, tie-lines, and the slope of the tie-line (STL) for [C(3)min][BF(4)]/[C(4)mim][BF(4)] + glucose + H(2)O systems were obtained at different temperatures of T = (278.15, 288.15, 298.15, and 308.15) K. Results show that, as the temperature decreases, the two-phase area expands and the STIL increases. Binodal curves were correlated using ail empirical equation, and tie-lines were correlated according to the Othmer-Tobias and Bancroft equations. These equations satisfactorily represented the experimental data. The molecular structure is used as ail argument to describe the phase-forming mechanism.