Galacto Configuration Research Articles

Structure of the disaccharide repeating unit of O-specific polysaccharide isolated from Aeromonas veronii strain Bs8 pathogenic to common carp (Cyprinus carpio)

The O-specific polysaccharide (OPS) was isolated from the lipopolysaccharide of Aeromonas veronii strain Bs8, which is pathogenic to common carp (Cyprinus carpio), after mild acid hydrolysis followed by gel-permeation chromatography. The high-molecular-mass OPS fraction was investigated using chemical methods, mass spectrometry, and 1H and 13C NMR spectroscopy techniques, including 2D homonuclear 1H,1H TOCSY, DQF COSY, NOESY, and heteronuclear 1H-detected 1H,13C HSQC, and HMBC experiments. The analysis revealed that the O-specific polysaccharide contains sugars with the galacto configuration of the ring and is composed of a disaccharide repeating unit with the following structure:

Structural Insights into the Binding of Sugar Receptors (Lectins) to a Synthetic Tricyclic Tn Mimetic and Its Glycopeptide Version

AbstractCycloadduct 1 is a conformationally constrained mimetic of the tumor‐associated Tn antigen. It maintains the 4C1 conformation and the α‐O‐glycosidic linkage of the natural epitopes. Due to its tricyclic structure, the anomeric linkage is constrained and its conformation “frozen”. Using saturation transfer difference NMR spectroscopy experiments, epitope mapping for binding by three lectins [i.e., from Erythrina cristagalli (ECL), human macrophages (MGL), and from Helix pomatia (HPA)] was carried out. Striking differences in the epitope viewed from the ligand's perspective were revealed by this comparison. Evidently, the structural change around the C‐2 position has a major impact, if the contact pattern to the ligand is not mostly restricted to galacto configuration with the axial hydroxyl group at C‐4, in combination with C‐3/C‐6. These measurements thus provide insights into actual contacts, which help predict applicability as an inhibitor for distinct lectins, and as an elicitor of specific antibodies.

‘Click’ glycosylation of peptides through cysteine propargylation and CuAAC

‘Click’ glycosylation of cysteine-containing peptides were carried out in good yield by Copper(I)-catalyzed Azide–Alkyne Cycloaddition (CuAAC). For that peptides were functionalized though direct propargylation of the cysteine residue allowing their use in CuAAC with suitable free or protected azido sugars of gluco, manno and galacto configuration. Among these free and protected glycopeptides a series of ‘glycoRGD’ peptides were obtained and submitted to in vitro platelet aggregation tests, showing that the pseudoglycosylation of the adhesion sequence lowers the IC50 value and thus could improve the in vivo pharmacokinetic properties.

Synthesis and in vitro evaluation of antifungal and cytotoxic activities of eugenol glycosides

Six eugenol glycosides were prepared in order to assess their antifungal activity against Candida species. They were synthesized by glycosylation of eugenol with the appropriate glycosyl bromides followed by deacetylation with sodium methoxide in methanol and were evaluated in vitro for their antifungal activity through a Mueller–Hinton broth microdilution method. The peracetyl glycoside (derivative 4) was the most promising one since it was able to inhibit growth of C. albicans, C. tropicalis and C. glabrata with IC50 values much lower than that of the prototype eugenol. Derivative 4 showed to be 160.0 and 3.4 times more potent than eugenol and fluconazole, respectively, against C. glabrata with low cytotoxity (selectivity index of 45). Moreover, it was possible to verify the positive effect of gluco configuration and lipophilicity on antifungal activity, since glucose peracetyl derivatives were more active than the free sugars of galacto configuration.

ChemInform Abstract: Convenient One‐Pot Synthesis of Thiosugars and Their Efficient Conversion to Polyoxygenated Cycloalkenes.

AbstractA one‐pot protocol for the synthesis of thiosugars with xylo, ribo, gluco, manno, fuco, and galacto configuration via thioetherification of diols with sodium sulfide is developed.

Synthesis of new C-glycosyl aza-β3-amino acids building blocks

New C-glycosylated Nβ-protected aza-β3-amino acid building blocks have been prepared from C-glycosyl aldehydes of gluco and galacto configuration by reductive amination and subsequent N-alkylation. These moieties were elaborated to β-dipeptides by elongation at the C- or the N-terminus establishing their ability to be incorporated in original glycosylated foldamers.

Epoxidation of glycals with oxone–acetone–tetrabutylammonium hydrogen sulfate: a convenient access to simple β- d-glycosides and to α- d-mannosamine and d-talosamine donors

The addition of a phase transfer catalyst during the epoxidation of perbenzylated glycals with oxone–acetone under biphasic conditions allows their complete epoxidation. The epoxides were readily transformed into methyl 1,2- trans-β- d-glycosides or 1,2- trans-β- d-glycopyranosyl azides ( d- gluco and- d- galacto configurations) bearing a free hydroxyl group at the 2-position. These glycosyl azides were converted to alkyl 1,2- trans-2-acetamido-2-deoxy-α- d-pyranosides or alkyl 2-allyloxycarbonylamino-2-deoxy-α- d-pyranosides ( d- manno and d- talo configurations) by a Staudinger reaction and a double inversion of configuration at C-1 and C-2.

ChemInform Abstract: Synthesis of 4-Epoxy-4-C-methyleneglycosylceramides, Potential Glycosyltransferase Inhibitors.

D-Glucose was transformed into the 4-deoxy-4-C-methylene derivative 1. Dihydroxylation of 1 and then selective O-tosylation afforded 4-C-(tosyloxymethyl)glucoside 3. Subsequent hydrogenolytic O-debenzylation, selective O-acetylation, treatment with a base, selective removal of the anomeric O-acetyl group, and then treatment with trichloroacetonitrile in the presence of a base furnished 4-epoxy-4-C-methyleneglucosyl donor 7 (α,β mixture). Reaction of 7 with 3-O-acyl-protected azidosphingosines 8a–c in the presence of Et2O.BF3 gave β-glycosides 9a–c. Compounds 9a–c were transformed into the corresponding glucosylceramide derivatives 10a–c by treatment with triphenylphosphane/water and acyl anhydrides. Satisfactory removal of the O-benzoyl protective group was difficult; however, O-acetyl and O-isobutyryl protective groups could be removed by methanolysis, thus affording from 10b, c the target molecules 11 and 12 with varying alkyl-chain length. The epoxide 16 with galacto configuration, readily obtained from 1, on treatment with p-toluenesulfonic acid furnished 4-C-(tosyloxymethyl)galactoside 18; this was transformed, as outlined for 3, into the target molecules 25b, c having galacto configuration in the sugar moiety.

Synthesis of anomeric sulfonamides and their behaviour under radical-mediated bromination conditions

O-Peracetylated methyl 3-( d-glycopyranosylthio)propanoates of β- d- gluco, and α- and β- d- galacto configurations were oxidized to the corresponding S,S-dioxides (sulfones) by Oxone ® or MCPBA. Oxidation of the β- d- gluco derivative with H 2O 2/Na 2WO 4 gave the corresponding S-oxide (sulfoxide). DBU-induced elimination of methyl acrylate from the β- d- gluco and β- d- galacto configured S,S-dioxides (sulfones) gave O-peracetylated β- d-glycopyranosyl-1- C-sulfinates which, on treatment with H 2NOSO 3H, furnished the corresponding β- d-glycopyranosyl-1- C-sulfonamides. Radical-mediated bromination of the protected methyl 3-(β- d-glycopyranosylthio)propanoate S,S-dioxides gave mixtures of 1- C- and 5- C-bromoglycosyl compounds. Similar brominations of the O-peracetylated β- d-glycopyranosyl-1- C-sulfonamides resulted in the formation of α- d-glycopyranosyl bromides and 1- C- and 5- C-bromoglycosyl sulfonamides. A rationale for these observations was proposed. Methyl 3-(β- d-glucopyranosylthio)propanoate, its S,S-dioxide, and β- d-glucopyranosyl-1- C-sulfonamide proved inefficient when tested as inhibitors of rabbit muscle glycogen phosphorylase b.

Structure determination of discoidin II from Dictyostelium discoideum and carbohydrate binding properties of the lectin domain

The social amoeba Dictyostelium discoideum adopts a cohesive stage upon starvation and then produces Discoidin I and II, two proteins able to bind galactose and N-acetyl-galactosamine. The N-terminal domain or discoidin domain (DS) is widely distributed in eukaryotes where it plays a role in extracellular matrix binding while the C-terminal domain displays sequence similarities to invertebrate lectins. We present the first X-ray structures of the wild-type and recombinant Discoidin II in unliganded state and in complex with monosaccharides. The protein forms a homotrimer which presents two binding surfaces situated on the opposite boundaries of the structure. The binding sites of the N-terminal domain contain PEG molecules that could mimics binding of natural ligand. The C-terminal lectin domain interactions with N-acetyl-D-galactosamine and methyl-beta-galactoside are described. The carbohydrate binding sites are located at the interface between monomers. Specificity for galacto configuration can be rationalized since the axial O4 hydroxyl group is involved in several hydrogen bonds with protein side chains. Titration microcalorimetry allowed characterization of affinity and demonstrated the enthalpy-driven character of the interaction. Those results highlight the structural differentiation of the DS domain involved in many cell-adhesion processes from the lectin activity of Dictyostelium discoidins.

Hantzsch-Type Three-Component Approach to a New Family of Carbon-Linked Glycosyl Amino Acids. Synthesis of C-Glycosylmethyl Pyridylalanines,

C-Glycosylmethyl pyridylalanines reported in this paper constitute a novel family of glycosyl amino acids that contain a pyridine ring linking the carbohydrate and amino acid residues. These amino acids may serve to prepare nonnatural glycopeptides displaying firmly bound carbohydrate fragments through a rigid and highly stable tether. A viable route to these new hybrid molecules has been opened via thermally induced Hantzsch-type cyclocondensation using an aldehyde-ketoester-enamino ester system. To one of these reagents was attached a C-glycosyl residue, while to another was bound an amino acid fragment. In a one-pot optimized methodology, the dihydropyridine was not isolated while its purification was carried out by removal of unreacted material and side products using polymer-supported scavengers. Then the dihydropyridine (mixture of diastereoisomers) was oxidized by a polymer-bound oxidant to give the target pyridine bearing the two bioactive residues. In this way a range of eight compounds (58-68% yield) was prepared in which the elements of diversity were (i) the gluco and galacto configurations of the pyranose ring, (ii) the alpha- and beta-configurations at the anomeric center, and (iii) the positions of the carbohydrate and amino acid sectors in the pyridine ring. The orthogonal functional group protection in these amino acids allowed their easy incorporation into oligopeptides via sequential amino and carboxylic group coupling.

Preparation of diamino pseudodisaccharide derivatives from 1,6-anhydro-β- d-hexopyranoses via aziridine-ring cleavage

Twelve positional isomers of diamino pseudodisaccharide derivatives with gluco–gluco configuration have been prepared using aziridine-ring cleavage of epimino derivatives of 1,6-anhydro-β- d-hexopyranoses of the d- allo, d- manno, and d- galacto configuration by 2-, 3-, and 4-amino derivatives of 1,6-anhydro-β- d-glucopyranose. The N-substitution of the aziridine ring by a 2-nitrobenzenesulfonyl group and ionic-liquid solvent ( N-methylpyridinium tosylate) was used to obtain cleavage products in high yield (64–93%). The cleavage reactions proceeded according to the Fürst–Plattner rule and only trans-diaxial stereoisomers were formed.

A study of n-pentenylorthoesters having manno, gluco and galacto configurations in regioselective glycosylations

Kochetkov’s extensive investigations of glycosyl orthoester and their analogs as glycosyl donors revealed that the alkyl derivatives were plagued by competition between the departing alcohol and the incoming acceptor. n-Pentenyl orthoesters (NPOEs) obviate competition by sequestering the departing pentenyl alcohol as a 2-halomethyl tetrahydrofuran. Exquisitely regioselective glycosidations of diol acceptors can be carried out with NPOEs triggered specifically with Yb(OTf) 3/NIS. However with Sc(OTf) 3, double glycosidation is the major reaction. manno, gluco and galacto NPOEs have been investigated. The latter two, which require a different experimental procedure for the manno counterpart, also give an excellent regioselectivity with Yb(OTf) 3, but the yields are much lower than with manno.

Modeling ring puckering in strained systems: application to 3,6-anhydroglycosides

Different conformations of methyl 3,6-anhydroglycosides with the β- d- galacto, α- d- galacto, and β- d- gluco configurations were studied by molecular mechanics (using the program mm3) and by quantum mechanical (QM) methods at the HF/- and B3LYP/6-31+G** levels, with and without solvent emulation. Using molecular mechanics, the energies were plotted against the ϕ, θ puckering coordinates of Cremer and Pople. In such strained systems, only two extreme conformations of the six-membered ring are likely: 1 C 4 and B 1,4, or any one close to either of them. Results show the preponderance of a distorted chair conformation over that of the distorted boat, though the energy difference is lower and the distortions are larger for the compound with the β- d- galacto configuration. For derivatives of this compound, experimental data in solution indicate both chair and boat forms, depending on the compound and the solvent, whereas for the remaining compounds, experimental data always show the preponderance of the chair conformation. The more accurate DFT calculations lead to the lower energy differences, suggesting that HF and mm3 underestimate the stability of the boat-like conformations. Similar studies on model compounds depict the importance of the anomeric effect in the conformational preferences.

Synthesis of 2-Amino-2-deoxy-β-D-galactopyranosyl-(1→4)-2-amino-2-deoxy-β-D-galactopyranosides: Using Various 2-Deoxy-2-phthalimido-D-galactopyranosyl Donors and Acceptors

A systematic study is presented of the efficiency of the most common glycosylation methods using standard 2-deoxy-2-phthalimidogalactopyranosyl donors ethyl 4-O-acetyl-3,6-di-O- benzyl-2-deoxy-2-phthalimido-1-thio-β-D-galactopyranoside (3a), 4-O-Acetyl-3,6-di-O-benzyl- 2-deoxy-2-phthalimido-β-D-galactopyranosyl bromide (4), 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranosyl fluoride (5b), O-(4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranosyl) trichloroacetimidate (7) and ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-galactopyranoside (8), pent-4-enyl 3,6-di-O-benzyl- and 3-O-allyl-6-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranoside (10a) and (10b) and pent-4-enyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-4-O-(trimethylsilyl)-β-D-galactopyranoside (11) as glycosyl acceptors in the synthesis of 2-amino-2-deoxy-β-D-galactopyranosyl-(1→4)-2-amino-2-deoxy-β-D-galactopyranosides 12, 16a and 17a. It was found that due to a low reactivity of the axial OH(4) group of glycosyl acceptors, disaccharides 16b and 17b with α(1→4) bond were also formed. The unexpected intermolecular migration of ethylsufanyl group from the reducing end of glycosyl acceptor 8 the reducing end of the activated form of glycosyl donor 4 in the glycosylation step to give ethylsulfanyl derivative 3a was proved. For preparation of the glycosyl donors and glycosyl acceptors with galacto configuration an approach based on epimerization of 4-O-mesyl derivatives of appropriate synthons with gluco configuration 2a and 2b was employed.

Crystal structure of penta- O-acetyl-β- d-galactopyranose with modeling of the conformation of the acetate groups

The crystal structure of penta- O-acetyl-β- d-galactopyranose was determined with Mo K α radiation at 150 K to R=0.029. The space group is P2 12 12 1, and the unit cell dimensions are, a=8.348, b=9.021 and c=25.418 Å. The ring has the usual 4 C 1 shape and O-6 is in the tg position as frequently observed for sugars having the axial galacto configuration at C-4. Conformations of the acetate groups were compared with those from the literature. Nearly eclipsed, ‘ Z’ conformations are found for the ester moieties, and the torsion angles for the sequence involving the ring hydrogen, carbon, alkoxy oxygen and carbonyl carbon for both 1 and related compounds are eclipsed-to-gauche. Orientations and conformations of the acetate substituents were modeled with both mm3 molecular mechanics and various levels of quantum mechanics theory. Higher levels of theory and more complete models provided better prediction of the experimental observations.

An easy route to seven-membered iminocyclitols from aldohexopyranosyl enamines

A new stereocontrolled and high yielding synthesis of biologically active polyhydroxyperhydroazepines is reported starting from easily available glycosylenamines (D- gluco, D- manno, and D- galacto configurations), which are transformed into 1,6-azaanhydropyranose derivatives. O- and N-Deprotection of the latter, followed by reduction with sodium cyanoborohydride, gives the target chiral iminocyclitols. The method is based on the capacity of the dialkoxycarbonylvinyl group to stabilize an amide ion, and the only limitation is the necessity for the starting glycosylenamine to have β-D-configuration. The inhibitory activity of several intermediate iminocyclitols and aldopyranosylenamines on different α- and β-glycosidases is also reported.

The saccharide–hydrazide linkage: molecular and crystal structures of the semicarbazide derivatives of d-glucose, d-galactose, and d-xylose, including a ‘forbidden’ conformation of the galactose derivative

The X-ray crystal structures of the semicarbazide derivatives of d-glucose, d-galactose, and d-xylose are described. All are glycopyranosyl derivatives in the solid state. The glucose semicarbazide crystallizes as a dihydrate. Two different conformations of the galactose semicarbazide are found, one having the gg side-chain orientation unfavorable for monosaccharides having the 4 C 1- d- galacto configuration. In the two other known examples, this conformation is stabilized by an intramolecular hydrogen bond, but in the current structure, the hydrogen bonds involving the side chain are intermolecular. In these semicarbazides the NNCO torsional angle is approximately 180°, in contrast to the angles of 0.60 and 13.9° in the two solid-state conformations of 2-benzoyl-1-(α- d-xylopyranosyl)hydrazine [Ernholt, B. V.; Thomsen, I. B.; Lohse, A.; Plesner, I. W.; Jensen, K. B.; Hazell, R. G.; Liang, X.; Jakobsen, A.; Bols, M. Chem. Eur. J. 2000, 6, 278–287]. The water molecules and the carbonyl oxygen are heavily involved in H-bonding.

A convenient route to higher sugars by two-carbon chain elongation using Wittig/dihydroxylation reactions.

The combination of a Wittig olefination and a dihydroxylation reaction constitutes a facile synthetic protocol for the transformation of unprotected carbohydrates into higher sugars. The Wittig reaction is carried out with tert-butyl or diphenylmethyl ester stabilized phosphoranes to give (E)-configured alpha,beta-unsaturated esters as the only products in most cases. These are dihydroxylated in a diastereoselective fashion using OsO(4)/NMO. The stereochemical outcome in the dihydroxylation follows Kishi's empirical rule and gives high diastereoselectivity (5:1-8:1) when starting from sugars with the 2,3-threo configuration. When starting from sugars with the 2,3-erythro configuration, the diastereoselectivity in the dihydroxylation is low (2:1-2.5:1). As a result, the Wittig/dihydroxylation protocol is most effective for producing higher sugars with the galacto configuration at the reducing end. The two steps can either be carried out individually or, more efficiently, as a one-pot procedure.

Homologation of O-Acetylated Methyl Hexopyranosides with a Grignard C1 Reagent

Three methyl 2,3,4-tri-O-acetyl-α-D-hexopyranosides of the manno, gluco, and galacto configuration were oxidized to the corresponding methyl hexodialdo-1,5-pyranosides and then reacted with allyloxymethylmagnesium chloride. Methyl heptopyranosides of the D- and L-glycero-α-D-manno-, -α-D-gluco, and -α-D-galacto configuration were obtained in moderate yields. Migration of the 4-O-acetyl group in the products was observed. An interpretation of the results was proposed.