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Reductive openings of cyclic acetals are widely used in modern synthetic organic chemistry for the regioselective introduction of protecting groups. A systematic study was performed on the applicability and efficacy of various hydride donor and protic or Lewis acid reagent combinations in the reductive ring opening of glucosidic 4,6-halobenzylidene acetals bearing an ortho-, meta-, and para-chloro- or -bromo substituent on the benzene ring. Most of the reagent combinations tested cleaved the 4,6-O-halobenzylidene acetal rings at O4 or O6 efficiently and with the expected regioselectivity. The LiAlH4-AlCl3 and the BH3·THF-TMSOTf combinations produced the 4-O-halobenzyl ether/6-OH products with complete regioselectivity and high yields. The use of Me3N·BH3-AlCl3 reagent system in toluene was also effective in cleaving the acetal ring at O6 but was accompanied by Al-chelation-assisted debenzylation side reactions. The NaCNBH3-HCl and the Et3SiH-BF3·Et2O combinations were highly effective in yielding the 6-halobenzyl ether/4-OH derivatives. Et3SiH, in combination with TfOH, produced the 6-O-ether/4-OH products in rapid reactions but also triggered silylation and reductive halobenzylation as secondary transformations. Reductive opening of the 1,3-dioxane ring of pyranosidic 4,6-O-halobenzylidene acetals by the proper reagent combination was found to be an efficient method for the regioselective introduction of versatile halobenzyl protecting groups onto the pyranose ring.

Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conjugation methods. Three series of derivatives bearing two lipophilic groups were synthesized by attaching bis-alkylthio maleimides directly or through linkers of different lengths to the glycopeptide. Access to the fourth and fifth series of compounds was achieved by click chemistry, introducing single alkyl/aryl chains directly or through a tetraethylene glycol linker to the same position. A sixth group of semisynthetic derivatives was obtained by sulfonylation of the N-terminus. Of the 42 lipophilic teicoplanin pseudoaglycon derivatives tested, about half showed broad activity against influenza A and B viruses, with some of them having reasonable or no cytotoxicity. Minor differences in the side chain length as well as lipophilicity appeared to have significant impact on antiviral activity and cytotoxicity. Several lipoglycopeptides were also found to be active against human coronavirus., Graphical abstract Image 1, Highlights • Multiple series of lipophilic teicoplanin pseudoaglycon derivatives were prepared. • Alkyl or aryl chains were coupled to the N-terminus by various conjugation methods. • The activity of new antibiotic derivatives was evaluated against influenza viruses. • Half of the 42 derivatives showed high activity against influenza A and B viruses. • The length and lipophilicity of the side chains influence the antiviral activity.

Radical-mediated addition reactions of thiols to O-peracetylated exo-galactal and exo-xylal with 2,2-dimethoxy-2-phenylacetophenone as the photoinitiator resulted in high yielding formation of the corresponding β-d-glycopyranosylmethyl-sulfide derivatives (2,6-anhydro-1-deoxy-1-S-substituted-1-thio-alditols) with exclusive regio- and very high stereoselectivity, including disaccharide mimicks with Gly-CH2-S-Gly scaffolds.

A new reagent system consisting of a Lewis acid such as BF3·Et2O or Cu(OTf)2, the mild protic acid hexafluoroisopropanol and the reducing quenching agent triethylsilane was elaborated for O-, N- and S-detritylation of nucleoside, carbohydrate and amino acid derivatives. The method is compatible with acetyl, silyl, acetal and Fmoc groups.

Photorhabdus asymbiotica is a gram-negative bacterium that is not only as effective an insect pathogen as other members of the genus, but it also causes serious diseases in humans. The recently identified lectin PHL from P. asymbiotica verifiably modulates an immune response of humans and insects, which supports the idea that the lectin might play an important role in the host-pathogen interaction. Dimeric PHL contains up to seven l-fucose-specific binding sites per monomer, and in order to target multiple binding sites of PHL, α-l-fucoside-containing di-, tri- and tetravalent glycoclusters were synthesized. Methyl gallate and pentaerythritol were chosen as multivalent scaffolds, and the fucoclusters were built from the above-mentioned cores by coupling with different oligoethylene bridges and propargyl α-l-fucosides using 1,3-dipolar azide-alkyne cycloaddition. The interaction between fucoside derivates and PHL was investigated by several biophysical and biological methods, ITC and SPR measurements, hemagglutination inhibition assay, and an investigation of bacterial aggregation properties were carried out. Moreover, details of the interaction between PHL and propargyl α-l-fucoside as a monomer unit were revealed using X-ray crystallography. Besides this, the interaction with multivalent compounds was studied by NMR techniques. The newly synthesized multivalent fucoclusters proved to be up to several orders of magnitude better ligands than the natural ligand, l-fucose.

A selection of nine derivatives of teicoplanin pseudoaglycon were tested in vitro against clinical vancomycin-resistant Enterococcus strains possessing vanA, vanB or both genes. The bacteria were characterized by PCR for the identification of their resistance genes. The tested compounds contain lipoic acid, different carbohydrates and aryl groups as lipophilic moieties. About one-third of the teicoplanin-resistant strains were shown to be susceptible to one or more of the glycopeptide derivatives.

The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal infections in cystic fibrosis patients. Multivalent mannoside derivatives were prepared as potential inhibitors of lectin BC2L-A, one of the virulence factors deployed by B. cenocepacia in the infection process. An (α1→2)-thio-linked mannobioside mimic bearing an azide functionalized aglycon was conjugated to different multivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by azide-alkyne 1,3-dipolar cycloaddition. The interaction between the glycoclusters and the mannose binding BC2L-A lectin from B. cenocepacia was examined by isothermal microcalorimetry, surface plasmon resonance, inhibition of yeast agglutination and analytical ultracentrifugation.

A series of lipophilic teicoplanin pseudoaglycon derivatives, including alkyl-, aryl-, calixarene- and protected sugar-containing conjugates, were prepared using azide-alkyne click chemistry. Out of the conditions applied, the CuSO

Introduction of a sulfonatomethyl moiety into the primary position of thioglycosides by nucleophilic displacement of the corresponding 6-O-triflate is described. The 1→6 migration of the anomeric group, which inevitably occurs through a bicyclic sulfonium ion intermediate, from conformationally flexible β-thioglycosides was prevented by using an α-thioglycoside or conformationally locked β-thioglycoside as the starting material. The thioglycoside 6-sulfonic acids showed excellent α-selectivity during synthesis of uronic acid containing heparinoid trisaccharides.

A new reagent system consisting of a Lewis acid such as BF3·Et2O or Cu(OTf)2, the mild protic acid hexafluoroisopropanol and the reducing quenching agent triethylsilane was elaborated for O-, N- and S-detritylation of nucleoside, carbohydrate and amino acid derivatives. The method is compatible with acetyl, silyl, acetal and Fmoc groups.

Two different series of (2→5)-α-linked homologous keto-oligosaccharides up to tri- and tetrasaccharide were synthesized by an iterative approach, using 3,4,7-tri-O-benzyl-5-O-(2-naphthyl)methyl-1-deoxy-1-ethoxysulfonyl-α-d-gluco-hept-2-ulopyranosyl chloride as a key building block. An iterative cycle consisted of a glycosylation step followed by selective cleavage of the (2-naphthyl)methyl group.

Glycosylation reactions of the ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranose were studied applying different acceptors under different conditions. Elimination side-reactions affording exo- and endoglycals occured in all cases, however, with different proportions. Glycosyl chloride donor was applied to glycosylate a trisaccharide acceptor obtaining a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide in high yield.

Ethyl acetoacetate-sugar derivatives were prepared by standard alkylation of primary or secondary hydroxyls of diacetonide-protected sugars with ethyl 4-chloroacetoacetate. The obtained D-fructose, D-galactose, D-glucose and D-allose derivatives were conjugated to C60 using the Bingel reaction to afford hydrolytically stable, ether-linked fullerene-carbohydrates. Conjugation of an ester-protected mannose derivative to the C60 scaffold was carried out by the combination of the acetoacetate chemistry with the azide-alkyne click reaction.

The 4-O-sulfuric esters of methyl 6-deoxy-α-L-talo- and -α-L-mannopyranoside were prepared. The first ester is a component of the glycopeptidolipid-type cell surface antigens of M. avium. The isosteric isomers (sugar-4-CH2-SO3Na) of both sulfate esters (sugar-4-O-SO3Na) were synthesized using free radical addition reactions between sugar-exomethylene derivatives and either thioacetic acid or NaHSO3. The addition products of thioacetic acid were converted into sugar-CH2-sulfonic acids by oxidation with oxone. Characteristic 1 H- and 13 C-NMR data are given and discussed.

It is found that α-thioglycosides and conformationally locked beta-thioglycosides can be successfully transformed into biologically 6-sulfonatomethyl derivatives.

Exo- and endocyclic double bonds of glycals and terminal double bonds of enoses were reacted with various thiols by irradiation with UV light in the presence of a cleavable photoinitiator. The photoinduced radical-mediated hydrothiolation reactions showed highly varying overall conversions depending not only on the substitution pattern and electron-density of the double bond but also on the nature and substitution pattern of the thiol partner. Out of the applied thiols thiophenol, producing the highly stabilized thiyl radical, exhibited the lowest reactivity toward each type of alkene. In most cases, the hydrothiolations took place with full regio- and stereoselectivities. Successful addition of 1,2 : 3,4-di-O-isopropylidene-6-thio-α-D-galactopyranose to a 2,3-unsaturated N-acetylneuraminic acid derivative, providing a (3 → 6)-S-linked pseudodisaccharide, demonstrated that the endocyclic double bond of Neu5Ac-2-ene, bearing an electron-withdrawing substituent, shows sufficient reactivity in the photoinduced thiol–ene coupling reaction.

Thio-linked mono- and bivalent mimetics of α(2→3) and α(2→6)-linked sialosides were prepared by photoinduced hydrothiolation of alkenes and alkynes with the 2-mercapto sialic acid. Thiosialylation of 6-O-allyl- or 3-O-allyl-substituted galactose derivatives has been carried out by the thiol–ene click reaction. Double thiosialylation has also been achieved via thiol–yne chemistry using propargylated galactose derivatives as the alkyne components and the peracetylated 2-mercapto sialic acid as the thiol.

Free-radical hydrothiolation of the endocyclic double bond of enoses is reported. Reaction between 2-acetoxy-d-glucal and a range of thiols including amino acid, peptide, glycosyl thiols, and sugars with primary or secondary thiol functions gave S-linked α-glucoconjugates and S-disaccharides with full regio- and stereoselectivity. Addition of glycosyl thiols to a 2,3-unsaturated glycoside also proceeded with good selectivity and afforded a series of 3-deoxy-S-disaccharides.

Selective cleavage of the (2-naphthyl)methyl (NAP) group in the presence of p-methoxybenzyl (PMB), benzyl and benzylidene groups was achieved by catalytic hydrogenation with a series of monosaccharides. At a disaccharide level, the PMB group was stable upon hydrogenolysis of the NAP, however, partial cleavage of benzyl ether functions was observed.

[939-26-4] C11H9Br (MW 221.10) InChI = 1S/C11H9Br/c12-8-9-5-6-10-3-1-2-4-11(10)7-9/h1-7H,8H2 InChIKey = RUHJZSZTSCSTCC-UHFFFAOYSA-N (2-naphthylmethylating agent for heteroatomic functional groups and a widely applicable protecting group for alcohols, thiols, and amides) Alternate Name: 2-(bromomethyl)naphthalene, NAPBr. Physical Data: mp 51–54 °C; bp 213 °C/100 mm Hg; Fp > 230 °F (110 °C). Solubility: soluble in nearly all organic solvents. Form Supplied in: commercially available, 96% pure, slightly yellowish solid. Handling, Storage, and Precautions: irritating, lachrymatory agent. Should be kept in a cool, dry place.

[77196-31-7] C13H14O2 (MW 202.25) InChI = 1S/C13H14O2/c1-14-13(15-2)12-8-7-10-5-3-4-6-11(10)9-12/h3-9,13H,1-2H3 InChIKey = DUWXVMIEMVFNGD-UHFFFAOYSA-N (reagent used for the protection of diols as the versatile 2-naphthylmethylene acetal) Alternate Name: 2-naphthaldehyde dimethylacetal. Physical Data: bp 141–143 °C/2 mm Hg; d 1.10 g cm−3. Solubility: soluble in alcohol, ether, and most organic solvents. Form Supplied in: colorless clear liquid. The title reagent is not commercially available, it can be prepared from 2-naphthaldehyde which is commercially available. Preparative Methods: trimethyl orthoformate and Amberlite IR 120 (H+) resin were added to a solution of 2-naphthaldehyde in methanol and stirred overnight at room temperature. The mixture was filtered, neutralized with aq NaHCO3, and evaporated. The residue was dissolved in dichloromethane, washed with water, dried over MgSO4, and evaporated in vacuum. The residue is a yellowish clear liquid, pure enough for synthesis (> 95%). Vacuum distillation can be applied for further purification which gives a colorless liquid. A preparative method without solvent has also been described.1 Handling, Storage, and Precautions: should be kept in a cool and dry place.

In order to characterise the presumed epitopes of arabinogalactans, isolated from the extract of the cell-cultured Echinacea purpurea, two oligosaccharides were synthesized. The whole synthetic route was based on the successful combination of the (methoxydimethyl)methyl (MIP) and the (2-naphthyl)methyl ether (NAP) protecting groups. A β-(1→6)-linked trigalactoside was prepared, which contained a NAP ether at position 2'.This protecting group was selectively removed using either DDQ or Pd-C/H 2 and the acceptor was ready for further glycosylation.We have used two arabinofuranosyl donor compounds: 2,3,5-tri-O-acetyl arabinofuranosyl trichloroacetimidate and a peracetylated α-(1→5)-linked diarabinofuranosyl trichloroacetimidate. For the deprotection of the tetra- and pentasaccharides a common procedure was used. All of the synthesized compounds were characterized by 1 H and 1 3 C NMR spectroscopy, as well as by MALDI-TOF mass-spectrometry.

For the characterization of the supposed epitope of an arabinogalactan, isolated from the extract of the cell-cultured Echinacea purpurea, the title hexasaccharide was synthesized. The whole synthetic route was based on the 6-O-(methoxydimethyl)methyl ether (MIP) protecting group strategy. 2-O-Benzyl-3,4-O-isopropylidene-6-O-(methoxydimethyl)methyl-β- d -galactopyranosyl-(1→6)-1,2:3,4-di-O-isopropylidene-α- d -galactopyranose was used to prepare the desired glycosyl donor and glycosyl acceptor both carrying a persistent O-benzyl group at position 2′. Reaction of the digalactose donor and the digalactose acceptor resulted in a β-(1→6)-linked galactose-containing tetrasaccharide in which OH-2′ and OH-2′′′ were substituted with benzyl groups. Hydrogenolytic removal of the benzyl groups of the tetragalactose compound gave the diol aglycon which was diarabinosylated in one step to furnish the protected target compound, whose deprotection led to the title hexasaccharide. All of the synthesized compounds were characterized by 1H and 13C NMR spectra, as well as by MALDI-TOF mass-spectrometry measurements.