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Modification of the water hydrogen bond network imposed by disaccharides is known to serve as a bioprotective agent in living organisms, though its comprehensive understanding is still yet to be reached. In this study, aiming to characterize the dynamical slowing down and destructuring effect of disaccharides, we performed broadband dielectric spectroscopy, ranging from 0.5 GHz to 12 THz, of sucrose and trehalose aqueous solutions. The destructuring effect was examined in two ways (the hydrogen bond fragmentation and disordering) and our result showed that both sucrose and trehalose exhibit an obvious destructuring effect with a similar strength, by fragmenting hydrogen bonds and distorting the tetrahedral-like structure of water. This observation strongly supports a chaotropic (structure-breaking) aspect of disaccharides on the water structure. At the same time, hydration water was found to exhibit slower dynamics and a greater reorientational cooperativity than bulk water because of the strengthened hydrogen bonds. These results lead to the conclusion that strong disaccharide-water hydrogen bonds structurally incompatible with native water-water bonds lead to the rigid but destructured hydrogen bond network around disaccharides. Another important finding in this study is that the greater dynamical slowing down of trehalose was found compared with that of sucrose, at variance with the destructuring effect where no solute dependent difference was observed. This discovery suggests that the exceptionally greater bioprotective impact especially of trehalose among disaccharides is mainly associated with the dynamical slowing down (rather than the destructuring effect). [ABSTRACT FROM AUTHOR]

Glycosylhydrolases of various origins were used to produce fucose-containing disaccharides with prebiotic potential using different donor substrates and l-fucose as the acceptor substrate. Eight different disaccharides were synthesized as follows: three β-d-galactosyl-l-fucosides with glycosidase CloneZyme Gly-001-02 using d-lactose as a donor substrate, two with a structure similar to prebiotics; one β-d-galactosyl-l-fucose with β-d-galactosidase from Aspergillus oryzae using d-lactose as a substrate donor; and four α-d-glucosyl-l-fucosides with α-d-glucosidase from Saccharomyces cerevisiae using d-maltose as a donor substrate. All disaccharides were purified and hydrolyzed. In all cases, an l-fucose moiety was present, and it was confirmed for β-d-galactosyl-l-fucose by mass spectrometry. High concentrations of l-fucose as the acceptor substrate enhanced the synthesis of the oligosaccharides in all cases. The three enzymes were able to synthesize fucose-containing disaccharides when l-fucose was used as the acceptor substrate, and the highest yield was 20% using β-d-galactosidase from Aspergillus oryzae. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A. oryzae β-gal immobilized on glyoxyl agarose was tested in CPBR for the first time. • Highest Y Lu obtained was 0.6 g·g−1 for continuous operation in a packed bed reactor. • Flow, substrate molar ratio and enzyme/inert support affected CPBR performance. • Lactulose synthesis in CPBR is a sound alternative to conventional batch synthesis. Abstract Lactulose synthesis from fructose and lactose in continuous packed-bed reactor operation with glyoxyl-agarose immobilized Aspergillus oryzae β-galactosidase is reported for the first time. Alternative strategies to conventional batch synthesis have been scarcely explored for lactulose synthesis. The effect of flow rate, substrates ratio and biocatalyst-inert packing material mass ratio (M B /M IM) were studied on reactor performance. Increase in any of these variables produced an increase in lactulose yield (Y Lu) being higher than obtained in batch synthesis at comparable conditions. Maximum Y Lu of 0.6 g·g−1 was obtained at 50 °C, pH 4.5, 50% w/w total sugars, 15 mL·min−1, fructose/lactose molar ratio of 12 and M B /M IM of 1/8 g·g−1; at such conditions yield of transgalactosylated oligosaccharides (Y TOS) was 0.16 g·g−1, selectivity (lactulose/TOS molar ratio) was 5.4 and lactose conversion (X Lactose) was 28%. Reactor operation with recycle had no significant effect on yield, producing only some decrease in productivity. [ABSTRACT FROM AUTHOR]

Iminosugars are an important class of natural products and have been subject to extensive studies in organic synthesis, bioorganic chemistry and medicinal chemistry, yet only a limited number of these studies are on glycosylated iminosugars. Here, a general route of synthesis is presented towards glycosylated 1‐deoxynojirimycin derivatives based on the oxidation–reductive amination protocol that in the past has also been shown to be a versatile route towards 1‐deoxynojirimycin. The strategy can be applied on commercial disaccharides, as shown in four examples, as well as on disaccharides that are not commercially available and are synthesized for this purpose, as shown by a fifth example. The synthesis of five deoxynojirimycin‐configured aza‐disaccharides, starting from their corresponding disaccharides and featuring a double reductive amination on 5‐keto‐aldehydes, that returns the stereochemistry of the reducing end d‐glucopyranose is presented. As starting materials disaccharides, which are available in bulk, can be used, and alternatively be obtained by chemical synthesis. [ABSTRACT FROM AUTHOR]

Abstract: Xylobiose sequestration in a helical aromatic oligoamide capsule was evidenced by circular dichroism, NMR spectroscopy, and crystallography. The preparation of the 5 kDa oligoamide sequence was made possible by the transient use of acid‐labile dimethoxybenzyl tertiary amide substituents that disrupt helical folding and prevent double helix formation. Binding of other disaccharides was not detected. Crystallographic data revealed a complex composed of a d‐xylobiose α anomer and two water molecules accommodated in the right‐handed helix. The disaccharide was found to adopt an unusual all‐axial compact conformation. A dense network of 18 hydrogen bonds forms between the guest, the cavity wall, and the two water molecules. [ABSTRACT FROM AUTHOR]

A new methodology for the synthesis of the most challenging heparin building block has been developed. Orthogonally protected l‐idosyl glycosyl donors were prepared by C5 epimerization of the corresponding thioglucosides using the hydroboration/oxidation method followed by a 4,6‐acetal formation. The α‐anomeric configuration was crucial, and the bulky C4 substituent was advantageous for the high l‐ido diastereoselectivity. The 4,6‐arylmethylene group proved to be a directing element in glycosylation, whereby stereoselective α‐idosylation could be achieved by using idosyl donors without a C‐2 participating group. [ABSTRACT FROM AUTHOR]

A mild and convenient method for the synthesis of α‐glycosyl chlorides in high 80–96 % yields within 15–30 min using 2‐chloro‐1,3‐dimethylimidazolinium chloride (DMC) is disclosed. The method has a wide substrate scope and is compatible with labile OH protecting groups, including benzyl, acetyl, benzoyl, isopropylidene, benzylidene, TBDMS (tert‐butyldimethylsilyl), and TBDPS (tert‐butyldiphenylsilyl) groups. The excellent α selectivity obtained in this reaction is attributed to in‐situ isomerization of β‐glycosyl chlorides to the more stable α‐glycosyl chlorides, as demonstrated by 1H NMR spectroscopic studies. Disarmed sugars with OBz or OAc groups at C‐2 were chlorinated at a faster rate but ismomerized (β→α) at a slower rate than armed sugars with an OBn group at C‐2. More importantly, the method enables highly desirable one‐pot glycosylation reactions to take place, thus allowing efficient syntheses of disaccharides and simple O‐glycosylated sugars in high overall yields without the need for separation or purification of the α‐glycosyl chloride donors. This method will be especially useful for direct glycosylation reactions using glycosyl chloride donors that are unstable upon separation and purification. [ABSTRACT FROM AUTHOR]

A metal-free catalytic method for the synthesis of 2-deoxy glycosides and disaccharides has been developed using stable 2-deoxy glucosyl and galactosyl acetate donors. They could react with a variety of acceptors in the presence of catalytic amount of TMSOTf at 0°C to form glycosides, glycoconjugates, and disaccharides with excellent α-selectivity (> 19:1) and yields (up to 99%) in a short time (0.5 h). With this expedient method, several new compounds against human K562 and SMMC7721 cell lines were obtained and tested with in vitro antitumor bioactivities. [ABSTRACT FROM AUTHOR]

Glycosides as glycosyl donors using FeCl3 have been described. Under optimal reaction conditions, three kinds of propargyl glycosides were found to react with steroids and sugar-derived glycosyl acceptors to afford the corresponding disaccharides and glycoconjugates in good to excellent yields (66-91%). Meanwhile, the method can also realize one-pot synthesis of disaccharides, making it an effective, affordable, and green glycosylation procedure. [ABSTRACT FROM AUTHOR]

FlAlyA is an endolytic enzyme with a preference for polymannuronate. The crystal structure and mutagenesis studies elucidated that the structural variations at outer uronate-binding subsites +2, +3 and −2 control the enzymatic properties of PL-7 family enzymes. Lys158 mutations changed the pH dependency and enhanced the production of mono- and disaccharides. [ABSTRACT FROM AUTHOR]

1,5-Regioisomeric triazole linked disaccharides have been synthesized and screened for their inhibitory properties against ribonuclease A (RNase A). The angular constraint-driven ‘crescent shaped’ inhibitors accommodated themselves into the enzyme active site. An improved enzyme inhibition was observed with increased H-bonding ability of polar functional groups in the modified disaccharides. In this series, introduction of two carboxyl groups in the furanose rings elicited the best result with an inhibition constant of 50 ± 3 µM. This is the first ever report on the use of disaccharides as RNase A inhibitors. [ABSTRACT FROM AUTHOR]

A series of aryl substituted derivatives of xylose and xylobiose was synthesized. Biological tests revealed high insecticidal activity in the resulting compounds. [ABSTRACT FROM AUTHOR]

Low molecular weight gelators are important for the study of supramolecular chemistry and have useful applications for biomaterials. Glycomimetics that are easily accessible and have useful gelation properties are especially interesting molecules. In this research, nine per- O -acetyl lactosyl- and thirteen per- O -acetyl maltosyl triazole derivatives were synthesized and analyzed. Most of the maltosyl triazoles and one of the lactosyl derivatives were found to be effective molecular gelators. The supramolecular gels were characterized using rheology and optical microscopy and they exhibited morphologies ranging from fibers to planar sheets. The self-assembling properties of selected lactosyl and maltosyl triazole derivatives were studied using 1 H NMR spectroscopy at different temperatures. The NMR studies revealed that the triazole moiety in these compounds played an important role in the formation of the supramolecular assembly, but the sugar moiety configurations are more influential towards gelation. Naproxen and chloramphenicol were used as the model drugs to assess the potential of these compounds in drug delivery applications. A pH responsive gelator showed faster delivery of chloramphenicol at mild basic conditions than neutral conditions. The effective disaccharide triazole-based molecular gelators are useful for the preparation of advanced soft materials that have potential applications as matrix for immobilization of drugs or biomolecules. [ABSTRACT FROM AUTHOR]

Gram-scale syntheses of two kinds of bleomycin disaccharides are described. l -gulose subunit 12 was accomplished with a novel and short route in six steps and 37% overall yield from 4 , which could be easily prepared from the commercially available inexpensive material d -sorbitol, while 6-deoxy- l -gulose subunit was synthesized in 11 steps in 8% yield from d -glucolactone. The disaccharides were then prepared in a previously reported glycosidation coupling of the 3- O -carbamoyl-mannosyl donor with the l -gulopyranoside acceptors. Both disaccharides were finally obtained in gram-scale and the total synthesis of disaccharide 2 was achieved the first time. [ABSTRACT FROM AUTHOR]

The synthesis of pseudodisaccharides based on an oxaphosphinane heterocycle is described. Disaccharide mimetics 5 and 6 were readily obtained through glycosylation of a hydroxy group with appropriately protected furanosyl or pyranosyl carbohydrates using a trichloroacetamidate coupling strategy. Selective or complete deprotection then produced the chiral pseudodisaccharides in good yields. [ABSTRACT FROM AUTHOR]

A series of thermoresponsive hydrogels containing covalently incorporated trehalose, the well-known protein stabilizing disaccharide, was synthesized with the aim to obtain bioprotective carriers for protein release. Smart materials with trehalose present only in cross-links or both in cross-links and as pending moieties, were fabricated by redox-initiated radical copolymerization, with N -isopropylacrylamide used as the main monomer. In order to modify thermoresponsive properties, hydrogels containing more hydrophilic comonomers, acrylamide or N -(2-hydroxyethyl)acrylamide, were also obtained. The susceptibility of the cross-linker to undergo acid-catalyzed hydrolysis was used to disintegrate the polymer network and estimate the composition of the synthesized materials. The properties of hydrogels, which include: swelling capacity, thermoresponsive behavior, rheological characteristic, internal microstructure and the rate of acid-catalyzed degradation, were found to be dependent on both trehalose as well as hydrophilic comonomers. BSA and β-Galactosidase were chosen as model proteins for the release study from obtained hydrogels. The release profiles were shown to vary significantly depending on hydrogel form, the polymer network composition and temperature. [ABSTRACT FROM AUTHOR]

Polyene macrolides such as nystatin A1 and amphotericin B have been known to be potent antifungal antibiotics for several decades. Because the therapeutic application of polyenes is restricted by severe side effects such as nephrotoxicity, various chemical and biological studies to modify the polyene structure have been conducted to develop less-toxic polyene antifungals. A newly discovered nystatin-like polyene compound NPP was shown to contain an aglycone that was identical to nystatin but harbored a unique di-sugar moiety, mycosaminyl- N-acetyl-glucosamine, which led to higher solubility and reduced hemolytic toxicity. Additionally, a NPP-specific second sugar extending gene, nppY, was recently identified to be responsible for the transfer of a second sugar, N-acetyl-glucosamine, in NPP biosynthesis. In this study, we investigated biosynthesis of the glycoengineered NPP analog through genetic manipulation of the NPP A1 producer, Pseudonocardia autotrophica KCTC9441. NypY is another second sugar glycosyltransferase produced by Pseudonocardia sp. P1 that is responsible for the transfer of a mannose to the mycosaminyl sugar residue of nystatin. We blocked the transfer of a second sugar through nppY disruption, then expressed nypY in P. autotrophica △nppY mutant strain. When compared with nystain A1 and NPP A1, the newly engineered mannosylated NPP analog showed reduced in vitro antifungal activity, while exhibiting higher nephrotoxical activities against human hepatocytes. These results suggest for the first time that not only the number of sugar residues but also the type of extended second sugar moiety could affect biological activities of polyene macrolides. [ABSTRACT FROM AUTHOR]

Nonsymmetrical 1,1′-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1′-glycosylation strategy for the synthesis of nonsymmetrical 1,1′-disaccharides with diverse configurations and sugar components. The strategy is based on the joined forces of a new class of configurationally stable glycoside acceptors and stereodirecting thioglycoside donors. The new glycoside acceptors feature a picoloyl (Pico) protecting group at the remote C4/C3 position that confers unusual stability on TMS glycosides under acidic conditions. [ABSTRACT FROM AUTHOR]

A disaccharide repeating unit of the O-antigen from Burkholderia ambifaria , 6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-O(CH 2 ) 3 NH 2 ( 1 ), and its dimer and trimer, 6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-(1 → 3)-6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-O(CH 2 ) 3 NH 2 ( 2 ) and 6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-(1 → 3)-6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-(1 → 3)-6-deoxy-β- d -Alt-(1 → 4)-α- d -Rha-O(CH 2 ) 3 NH 2 ( 3 ), were synthesized via a convergent strategy. The key disaccharyl thioglycoside 4 as a glycosyl donor was stereoselectively assembled by glycosylation of rhammnosyl acceptor 5 with 6-deoxy-altrosyl trichloroacetimidate donor 6b . The glycosidation of 4 with 3-azidopropanol followed by global deprotection afforded the target disaccharide 1 . Further elongation of the carbohydrate chain of this glycosidation product with the disaccharyl donor 4 followed by global deprotection generated rapidly the dimeric tetrasaccharide 2 and the trimeric hexasaccharide 3 in a convergent [2 + 2] and [2 + 2 + 2] manner, respectively. [ABSTRACT FROM AUTHOR]

Rare sugars have recently attracted much attention because of their potential applications in the food, nutraceutical, and pharmaceutical industries. A systematic strategy for enzymatic production of rare sugars, named Izumoring, was developed > 10 years ago. The strategy consists of aldose-ketose isomerization, ketose C-3 epimerization, and monosaccharide oxidation-reduction. Recent development of the Izumoring strategy is reviewed herein, especially the genetic approaches to the improvement of rare sugar-producing enzymes and the applications of target-oriented bioconversion. In addition, novel non-Izumoring enzymatic approaches are also summarized, including enzymatic condensation, phosphorylation-dephosphorylation cascade reaction, aldose epimerization, ulosonic acid decarboxylation, and biosynthesis of rare disaccharides. [ABSTRACT FROM AUTHOR]

Crystalline acetylated ethyl 2-azido-2-deoxy-1-thio-α- d -cellobioside has been prepared on a multigram scale from cellobiose in an overall yield of 23% with no chromatography required and converted after deacetylation into the 4′,6′- O -benzylidene and 4′,6′- O -benzylidene-6- O -TBDMS protected derivatives. Applying a number of regioselective benzylation methods on these gave access to a variety of regioselectively protected derivatives, both mono-ols (2′- and 3-OH), diols (2′,6-, 2′,3-, and 3,6-di-OH), and triols (2′,3,6- and 2′,3′,3-tri-OH). A number of these derivatives were further processed by benzoylation followed by removal or opening of the benzylidene acetal and selective oxidation of the exposed primary alcohol to give heparin building block intermediates comprising a range of possible sulfation patterns. [ABSTRACT FROM AUTHOR]

Free-radical hydrothiolation of O-peracylated 1-C-(carbamoyl-, methoxycarbonyl- and cyano) substituted glycals with a range of sugar derived thiols gave the corresponding β-manno type 3-deoxy-3-S-disaccharides with full regio- and stereoselectivity. The configuration of the glycals (arabino vs. lyxo) and the size of the protecting groups had no significant effect on the outcome of the transformations. Formation of by-products was tracked down by LCMS studies and correlated with the electron density of the double bonds to show that the reactions were synthetically useful with a COOMe and especially with a CONH2 group as the 1-C-substituent. [ABSTRACT FROM AUTHOR]

As part of a search for selective, mechanism-based covalent inhibitors of human pancreatic α-amylase we describe the chemoenzymatic synthesis of the disaccharide analog α-glucosyl epi-cyclophellitol, demonstrate its stoichiometric reaction with human pancreatic α-amylase and evaluate the time dependence of its inhibition. X-ray crystallographic analysis of the covalent derivative so formed confirms its reaction at the active site with formation of a covalent bond to the catalytic nucleophile D197. The structure illuminates the interactions with the active site and confirms OH4' on the nonreducing end sugar as a good site for attachment of fluorescent tags in generating probes for localization and quantitation of amylase in vivo. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease. [ABSTRACT FROM AUTHOR]

A series of spacer-armed lactose derivatives with one or two O-sulfo groups in various positions, namely, 6- O-Su-Lac, 3´,6- O-Su2-Lac, 6´- O-Su-Lac, 6,6´- O-Su2-Lac, and 3´- O-Su-Lac (Su = SOH), was synthesized starting from the same precursor. All sulfated disaccharides were obtained in the form of 2-aminoethyl glycosides. [ABSTRACT FROM AUTHOR]

Terminal disaccharide fragment of phenolic glycolipid from Mycobacterium leprae (PGL-I) was synthesized as a glycoside with 4-(2-aminoethoxy)phenyl aglycon. The obtained 4-(2-aminoethoxy)phenyl 4- O-(3,6-di- O-methyl-β- d-glucopyranosyl)-2,3-di- O-methyl-α- l-rhamnopyranoside was used for the synthesis of a series of neoglycoconjugates with bovine serum albumin with different degrees of substitution. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to develop and validate an analytical method to determine the presence of hyaluronic acid derived disaccharides in equine synovial fluid. Findings: A high-performance liquid chromatography method for the determination of hyaluronic acid derived unsaturated disaccharides in equine synovial fluid was developed and validated. The method is based on the measurement of unsaturated disaccharides released by digestion of linear hyaluronic acid molecules. The method showed linearity (r2 = 0.996) over the full working concentration range 0.89-30 mg/l. Relative standard deviation of intra- and inter-day precision ranged from of 4.3-6.7% and 7.1-7.8% respectively. The detection limit was 0.3 mg/l corresponding to 20 mg/l in synovial fluid. Accuracy of the assay was 97-103%. This method was evaluated by determining the concentration of unsaturated disaccharides from hyaluronic acid in synovial fluid of horses with lameness in the metacarpo-/metatarsophalangeal joint localized with positive response to intra-articular anesthesia. Conclusions: The described method is valid for determination of hyaluronic acid derived disaccharides in equine synovial fluid. This method was applied to a larger research project dealing with a new form of intra-articular therapy in horses with arthritic diseases. [ABSTRACT FROM AUTHOR]

Disaccharide nucleosides constitute an important group of naturally-occurring sugar derivatives. In this study, we report on the synthesis of disaccharide nucleosides by the direct O-glycosylation of nucleoside acceptors, such as adenosine, guanosine, thymidine, and cytidine, with glycosyl donors. Among the glycosyl donors tested, thioglycosides were found to give the corresponding disaccharide nucleosides in moderate to high chemical yields with the above nucleoside acceptors using p-toluenesulfenyl chloride (TolSCl) and silver triflate (AgOTf) as promoters. The interaction of these promoters with nucleoside acceptors was examined by 1H NMR spectroscopic experiments. [ABSTRACT FROM AUTHOR]

Synthesis of an array of differentially sulfated GlcN–IdoA disaccharides, accessible on good scale, directly from l -iduronate components is described. These are specifically directed to provide the sulfation variability at the key most common biologically relevant sulfation-variable l -IdoA O-2 and d -GlcN O-6 and amino sites of this heparin disaccharide. This sulfation-varied matrix has allowed the first evaluation of using Raman/ROA spectroscopy to characterize changes in spectra as a function of both site and level of sulfation with pure, defined heparin-related disaccharide species. This provides analysis of both similarities and differences to digest native heparin and this shows evidence of different types of changes in conformations and conformational freedom as a function of some specific sulfation changes at the disaccharide level. It is anticipated that this data set will open the way for applications to further site-specific sulfated saccharides and demonstrates the capability offered by Raman–ROA towards fingerprinting sulfation in heparin fragments. [ABSTRACT FROM AUTHOR]

Synthesis of amphiphilic, cyclic di- and tetrasaccharides, which incorporate a methylene moiety at the inter-glycosidic bond, is reported. The amphiphilic properties of the new cyclic tetrasaccharide host were identified through assessing the solubilities of guests in aqueous and in organic solvents. The glycosidic bond stability of the cyclic tetrasaccharide under aqueous acidic condition was also verified. [ABSTRACT FROM AUTHOR]

The facile synthesis of a partially protected OSW-1 disaccharide moiety, having a 2-O-p-methoxybenzoyl-β-D-xylopyranosyl-(1 → 3)-2-O-acetyl-L-arabinopyranoside structure, was elaborated by glycosylation in aβ-stereoselective fashion. The xylopyranose donors were synthesized by a short synthetic approach via convenient selective 1,2-diacetal protection of 3,4-trans-diequatorial hydroxyl group. Regioselective ring opening of 1,2-diacetal-protected substrates efficiently led to the arabinopyranose acceptor with a free 3-hydroxyl group. Glycosylation of the xylopyranose donor with the arabinopyranose acceptor provided theβ-disaccharide. [ABSTRACT FROM AUTHOR]

A facile and stereoselective method for Ferrier glycosylation was developed using ruthenium(III) chloride. Using this protocol, the glycal donor reacted smoothly with several acceptors comprising different functionalities to afford corresponding 2,3-unsaturated glycosides in good to excellent yields. [ABSTRACT FROM AUTHOR]

Highlights: [•] The synthesis of beta-d-GlcNAc-(1→4)-d-Glc disaccharide starting from lactose is described. [•] The approach involves the transformation of the beta-d-galactopyranosyl unit into a N-acetyl-beta-d-glucosaminyl one. [•] The conversion of the β-d-talopyranosyl disaccharide into the β-d-mannopyranosyl one is achieved by stereoselective hydroboration–oxidation. [•] The β-d-mannopyranosyl unit is transformed into the beta-d-N-acetyl-glucosaminyl one by amination with inversion of configuration by SN2 displacement. [Copyright &y& Elsevier]

A series of unique nonreducing disaccharides, galactopyranosyl-(1→2)-N-acetylneuraminic acids and glucopyranosyl-(1→2)-N-acetylneuraminic acids, which hadN-acetylneuraminic acid linked to the anomeric position of another sugar, were synthesized. In these syntheses, the anomeric thiophenyl group of phenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside and phenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside was deprotected selectively to afford the corresponding hemiacetals that were used as glycosyl acceptors. These glycosyl acceptors were then coupled with phenyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate usingN-iodosuccinimide and trifluoromethanesulfonic acid as promoters in acetonitrile at −30°C, followed by sequential deprotection of the acetyl, methyl ester, and benzyl groups, to afford the title compounds. The ability of neuraminidase to hydrolyze these compounds was evaluated, and a correlation between the hydrolysis rates and structures was observed. [ABSTRACT FROM AUTHOR]

A simple multiple collision model for collision induced dissociation (CID) in quadrupole was applied for the estimation of the activation energy (E) of the fragmentation processes for lithiated and trifluoroacetated disaccharides, such as maltose, cellobiose, isomaltose, gentiobiose, and trehalose. The internal energy-dependent rate constants k(E) were calculated using the Rice-Ramsperger-Kassel-Marcus (RRKM) or the Rice-Ramsperger-Kassel (RRK) theory. The E values were estimated by fitting the calculated survival yield (SY) curves to the experimental ones. The calculated E values of the fragmentation processes for lithiated disaccharides were in the range of 1.4-1.7 eV, and were found to increase in the order trehalose < maltose < isomaltose < cellobiose < gentiobiose. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Selective conversion of biomass derived carbohydrates into fine chemicals is of great significance for the replacement of petroleum feedstocks and the reduction of environmental impacts. Levulinic acid, 5-hydroxymethyl furfural (HMF) and their derivatives are recognized as important precursor candidates in a variety of different areas. In this study, the synthesis, characterization, and catalytic activity of acidic TiO2 nanoparticles in the conversion of biomass derived carbohydrates were explored. This catalyst was found to be highly effective for selective conversion to value-added products. The nanoparticles exhibited superior activity and selectivity towards methyl levulinate from fructose in comparison to current commercial catalysts. The conversion of fructose to methyl levulinate was achieved with 80% yield and high selectivity (up to 80%). Additionally, conversions of disaccharides and polysaccharides were studied. Further, the production of versatile valuable products such as levulinic esters, HMF, and HMF-derived ethers was demonstrated using the TiO2 nano-sized catalysts in different solvent systems. [ABSTRACT FROM AUTHOR]

Highlights: [•] Trichinella spiralis. [•] Synthesis of cell surface N-glycan. [•] 1,2-cis-β Glycosidic linkages. [•] Protein carbohydrate interaction study. [•] Saturation transfer difference (STD) NMR. [ABSTRACT FROM AUTHOR]

Abstract: NIS/NaN3 mediated ring opening of various donor–acceptor cyclopropanes has been investigated. The study shows the necessity of the donor oxygen lone pair in such ring opening reactions. This methodology has been utilized in the synthesis of C-1 linked pseudodisaccharides through the use of click chemistry. [Copyright &y& Elsevier]

The oxidation of per- O-acetyl S-(1→3)- and S-(1→4)-linked thiodisaccharides containing glucose, gulose and galactose residues with an excess of m-chloroperbenzoic acid gave the corresponding sulfoxides or sulfones. Sulfones were formed when the oxidation reaction was left for longer times. The sulfoxides were obtained as diastereomeric mixtures due to the chirality of the sulfur atom. Both diastereoisomers of the S-(1→3)-linked thiodisaccharide sulfoxides were isolated by column chromatography, whereas the S-(1→4)-linked analogues could not be separated. The absolute configuration of the sulfur stereocentre of the sulfoxides was assigned using NMR spectroscopy, taking into account the preferred conformations of the molecules, and the shielding/deshielding of proton signals caused by the anisotropy of the S=O bond and related effects. Most of the thiodisaccharide sulfoxides were successfully O-deacetylated with MeOH/Et3N/H2O, but the sulfones underwent elimination reactions under these conditions. Therefore, the oxidation was performed on unprotected thiodisaccharides, and the corresponding sulfones were obtained in very good yields. [ABSTRACT FROM AUTHOR]

β-Galactosidase from Aspergillus oryzae was used for the production of galactosyl-xylose. This disaccharide is well known as a fragment of the highly concerved linkage region between the core protein and the polysaccharide chain (glycosaminoglycan) in proteoglycans of connective tissue. At the same time, galactosyl-xylose is a substrate analog of lactose and has a potential application in diagnostics of lactase insufficiency (lactose intolerance). In the order to optimize the conditions of transglycosylation reaction some parameters were examined. The ratio of donors (oNPGal, oNPGlc) and acceptor (xylose), enzyme concentration, temperature and pH were investigated and optimal conditions were established (10:1, 6520 IU, 40 °C and pH 5.5, respectively). The products of the enzyme reaction were analyzed by TLC. It was observed that b-galacosidase from Aspergillus oryzae transferred galactose and glucose from lactose used as a substrate and produced galactosyl-xylose and glucosyl-xylose. [ABSTRACT FROM AUTHOR]

Over the past decade, disaccharide phosphorylases have received increasing attention as promising biocatalysts for glycoside synthesis. Unfortunately, these enzymes typically have a very low affinity for non-carbohydrate acceptors, which urges the addition of cosolvents to increase the dissolved concentration of these acceptors. However, commonly applied solvents such as methanol and dimethyl sulfoxide (DMSO) are not compatible with many intended applications of carbohydrate-derived products. In this work, the solubility of a wide range of relevant acceptors was assessed in the presence of ionic liquids (ILs) as alternative and ‘green’ solvents. The IL AMMOENG 101 was found to be the most effective cosolvent for compounds as diverse as medium- and long-chain alcohols, flavonoids, alkaloids, phenolics and terpenes. Moreover, this IL was shown to be less deleterious to the stability and activity of sucrose phosphorylase than the commonly used dimethyl sulfoxide. To demonstrate the usefulness of this solvent system, a process for the resveratrol glycosylation was established in a buffer containing 20% AMMOENG 101, 1 M sucrose and saturated amounts of the acceptor. A single regioisomer 3-O-α-d-glucopyranosyl-(E)-resveratrol was obtained as proven by NMR spectroscopy. [ABSTRACT FROM AUTHOR]

AlfB and AlfC α-L-fucosidases from Lactobacillus casei were used in transglycosylation reactions, and they showed high efficiency in synthesizing fucosyldisaccharides. AlfB and AlfC activities exclusively produced fucosyl-α-1,3-N-acetylglucosamine and fucosyl-α-1,6-N-acetylglucosamine, respectively. The reaction kinetics showed that AlfB can convert 23% p-nitrophenyl-α-L-fucopyranoside into fucosyl-α-1,3-N-acetylglucosamine and AlfC at up to 56% into fucosyl-α-1,6-N-acetylglucosamine. [ABSTRACT FROM AUTHOR]

Abstract: Nucleotide-activated di- and oligosaccharides represent a novel class of glycoconjugates. They are components of human milk with still unknown biological function. Synthetic access to a wide range of nucleotide di- and oligosaccharides would also facilitate their utilization as donor substrates or inhibitors of Leloir-glycosyltransferases. We here present for the first time the synthesis of β1-3-linked nucleotide activated disaccharides by recombinant β3-galactosidase C from Bacillus circulans. UDP-Glc, UDP-GlcNAc, and UDP-GalNAc reacted as acceptor substrates in the transglycosylation reaction with p-nitrophenyl-β-galactoside as donor substrate. In an attempt to optimise the transglycosylation reaction, focused microwave irradiation was investigated. In comparison to conventional thermal heating product compositions and product yields were affected by microwave irradiation and depended on the used acceptor substrate. Microwave irradiation was advantageous for syntheses with UDP-GlcNAc as preferred acceptor substrate of β3-galactosidase C. The β1,3 linked UDP-disaccharide was the main product with minor fractions of UDP-tri- and UDP-tetrasaccharide. In summary, access to important UDP-disaccharides such as UDP-LacNAc type 1 and UDP-Thomsen-Friedenreich(T)-antigen was accomplished for further studies of their role as donor substrates or inhibitors of glycosyltransferases. [Copyright &y& Elsevier]

Abstract: In the present study, commercially available whey was used as a lactose source, and immobilized β-galactosidase and glucose isomerase were used to synthesize lactulose from whey lactose in the absence of fructose. Optimal reaction conditions, such as lactose concentration, temperature, ionic strength of the buffer, and ratio of immobilized enzymes, were determined to improve lactulose synthesis using immobilized enzymes. Lactulose synthesis using immobilized enzymes improved markedly after optimizing the reaction conditions. When the lactulose synthesis was carried out at 53.5°C using 20% (w/v) whey lactose, 12U/ml of immobilized β-galactosidase and 60U/ml of immobilized glucose isomerase in 100mM sodium phosphate buffer at pH 7.5, the lactulose concentration and specific productivity were 7.68g/l and 0.32mg/Uh, respectively. Additionally, when the immobilized enzymes were reused for lactulose synthesis, their catalytic activity was 57.1% after 7 repeated uses. [Copyright &y& Elsevier]

Abstract: A facile synthesis of 6′-deoxy-6′-fluorosucrose has been developed. The title compound is available in six linear steps in 44% overall yield from commercially available sucrose. The synthesis involves rapid and convenient fluorination and deprotection conditions. This procedure would be very useful for the incorporation of radioactive [18F]. [Copyright &y& Elsevier]

Trehalose is a unique disaccharide capable of protecting proteins against environmental stress. A novel trehalose synthase (TreS) gene from Rhodococcus opacus was cloned and expressed in Escherichia coli Top10 and BL21 (DE3) pLysS, respectively. The recombinant TreS showed a molecular mass of 79 kDa. Thin layer chromatography (TLC) result suggested that this enzyme had the ability to catalyze the mutual conversion of maltose and trehalose. Moreover, high-performance liquid chromatography (HPLC) result suggested that glucose appeared as a byproduct with a conversion rate of 12 %. The purified recombinant enzyme had an optimum temperature of 25 °C and pH optimum around 7.0. Kinetic analysis revealed that the K for trehalose was around 98 mM, which was a little higher than that of maltose. The preferred substrate of TreS was maltose according to the analysis of k/ K. Both 1 and 10 mM of Hg, Cu and Al could inhibit the TreS activity, while only 1 mM of Ca and Mn could increase its activity. Five amino acid residues, Asp, Glu, Asp, His and His, were shown to be conserved in R. opacus TreS, which were also important for α-amylase family enzyme catalysis. [ABSTRACT FROM AUTHOR]

Abstract: Dipyrranes bearing peracetylated mono- or disaccharidic C-1-deoxyalditol moieties were prepared from d-galactose, d-glucose, d-mannose, and lactose. A partially hydrolyzed polysaccharide (agarose) was also used as starting material for the synthesis of a disaccharide-containing C-glycoside dipyrrane. These compounds were synthesized as follows: the sugar starting materials were first submitted to a mercaptolysis–acetylation one-pot procedure (EtSH/HCl–Ac2O/pyridine). The resulting peracetylated diethyl dithioacetals were converted into dipyrranes through carbonyl deprotection (H5IO6, THF–Et2O) followed by TFA-catalyzed pyrrole condensation with yields up to 62%. Overall yields from sugar starting materials were up to 49%. [Copyright &y& Elsevier]

Abstract: Here we report a high yielding, stereoselective synthesis of the naturally occurring 1,1′-disaccharide neotrehalosadiamine (NTD) and some related analogs. Following an eleven-step sequence, seven of which did not require chromatographic separation, NTD was generated in 60% overall yield from the inexpensive, commercially available precursor 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. The key α,β-linkage of NTD was formed in a highly stereoselective manner by taking advantage of the participating effect of the acyl group at O-2 of the donor glycoside. The influence of electronic effects of disarmed, armed, and superarmed glycosyl donors and acceptors on the outcome of 1,1′-glycosidation was also observed. Antibacterial studies using NTD and its analogs show detectable but weak anti-staphylococcal activity. [Copyright &y& Elsevier]

Methyl 2,3-di-O-benzyl-1-deoxy-1-(prop-2-enyl)-α-D-galactopyranuronate and benzyl 2,3-di-Obenzyl- 1-deoxy-1-(prop-2-enyl)-α-D-galactopyranuronate were prepared as glycosyl acceptors. The glycosyl donors benzyl 4-O-acetyl-2,3-di-O-benzyl-1-(trichloroacetimidoyloxy)-α-Dgalactopyranosyluronate and benzyl 4-O-acetyl-2,3-di-O-benzyl-1-(trichloroacetimidoyloxy)-β- D-galactopyranosyluronate were synthesized in 98% and 76% yields respectively. Disaccharides methyl (methyl 4-O-acetyl-2,3-di-O-benzyl-α/β-D-galactopyranosyluronate)-(1→4)-2,3-di-Obenzyl- 1-deoxy-1-(prop-2-enyl)-α-D-galactopyranuronate and benzyl (benzyl 4-O-acetyl-2,3-di- O-benzyl-α/β-D-galactopyranosyluronate)-(1→4)-2,3-di-O-benzyl-1-deoxy-1-(prop-2-enyl)-α-Dgalactopyranuronate were synthesized in 53% and 44% yields respectively and with moderate stereoselectivity. The synthesis of 1,2-O-acetyl-3,4-di-O-benzyl-L-rhamnopyranose (α/β) and 2- O-acetyl-1-bromo-3,4-di-O-benzyl-α-L-rhamnopyranosyl suitable as glycosyl donors is described. The disaccharide methyl (2-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranosyl)-(1→4)- 2,3-di-O-benzyl-1-deoxy-1-(prop-2-enyl)-α-D-galactopyranuronate, and benzyl (2-O-acetyl-3,4- di-O-benzyl-α-L-rhamnopyranosyl)-(1→4)-2,3-di-O-benzyl-1-deoxy-1-(prop-2-enyl)-α-D-galactopyranuronate were obtained in 54% and 56% yield respectively. [ABSTRACT FROM AUTHOR]

We report the chemical synthesis of a series of disaccharides of arabinofuranose with a glycosidic sulfur linker as mimics of the acceptor for arabinofuranosyltransferases with and without using any activator to avoid any complex reactions. These analogs were tested for in vitro activity against MTB strain H37Ra and 3 MAC clinical isolates. MICs were determined using a colorimetric microdilution broth assay. Bactericidal activity was studied with kill curves over a period of seven days. Intracellular activity against MTB H37Ra was determined in the Mono Mac 6 (MM6) human monocytic cell line. [ABSTRACT FROM AUTHOR]