Pyranosyl Bromide Research Articles

Synthesis of 2-Indolyl C-Glycoside Neopetrosins A and C and Congeners via Ni-Catalyzed Photoreductive Cross-Coupling.

The synthesis of neopetrosins A and C, two 2-indolyl C-α-d-mannopyranosides, and their congeners has been realized via a direct Ni/photoredox-catalyzed reductive coupling of 3-methoxycarbonyl-2-iodo-1H-indoles with pyranosyl bromides.

Phenanthroline Catalysis in Stereoselective 1,2-cis Glycosylations.

The National Research Council's report in 2012 recognized glycosidic bond forming (glycosylation) reactions as critical due to the central importance of carbohydrates to the glycosciences. This report emphasized the need for the development of reproducible and broadly applicable glycosylation technologies to facilitate the stereoselective synthesis of biomedically relevant glycan libraries for tool development and for research applications by nonspecialists. In response to this report with NIH Common Fund support, the publications of new catalytic diastereoselective glycosylation protocols, some with broad generality under mild conditions, have been recently reported by our group and others. These recent discoveries have also advanced the understanding of the glycosylation reaction mechanism involving the coupling of a sugar electrophile bearing a leaving group at its C1-anomeric center with an alcohol nucleophile. This glycosidic bond forming reaction can lead to a mixture of two stereoisomers that differ in the configuration of the anomeric center.In our group, we discovered that readily available phenanthroline, a rigid and planar organic compound with two fused pyridine rings, could be utilized as a nucleophilic catalyst to promote highly diastereoselective glycosylation of an alcohol nucleophile with a sugar bromide electrophile. The phenanthroline catalysis process allows access to a myriad of high yielding and diastereoselective 1,2-cis pyranosides and furanosides. This catalyst-controlled approach has been applied to the synthesis of a potential vaccine adjuvant α-glucan octasaccharide. For pyranosyl bromide electrophiles, an extensive mechanistic investigation illustrated that two phenanthrolinium ion intermediates, a 4C1 chair-liked equatorial-conformer and a B2,5 boat-like axial-conformer, are formed in a ratio of 2:1 (equatorial/axial). To obtain high levels of axial-1,2-cis selectivity, a Curtin-Hammett scenario was proposed wherein interconversion of the 4C1 equatorial-conformer and B2,5 axial-conformer is more rapid than nucleophilic addition. Hydroxyl attack takes place from the axial-face of the more reactive 4C1 chairlike equatorial intermediate to afford an axial-1,2-cis glycoside product. The phenanthroline catalysis system is applicable to a number of furanosyl bromide electrophiles to provide the challenging 1,2-cis substitution products in good yield and diastereoselectivity. NMR experiments and density-functional theory (DFT) calculations support an associative mechanism in which the rate-determining step takes place from an invertive displacement of the faster reacting furanosyl phenanthrolinium ion intermediate with an alcohol nucleophile. Overall, this work stands at the underdeveloped intersection of operationally simple conditions, catalysis, and stereocontrolled glycosidic bond formation, each of which represents an important theme in the preparation of biologically important oligosaccharides and glycopeptides for applications to human health and medicine.

Alkyl Radical-Free Cu(I) Photocatalytic Cross-Coupling: A Theoretical Study of Anomerically Specific Photocatalyzed Glycosylation of Pyranosyl Bromide.

Previously, we reported a visible light-activated Cu(I) photocatalyst capable of facilitating C-O bond formation of glycosyl bromides and aliphatic alcohols with a high degree of diastereoselectivity. This catalyst functions equally well in the presence of radical traps, suggesting an entirely inner sphere mechanism atypical for heteroleptic Cu photocatalysis. Further, experimental estimates put the chromophore reducing power at -1.30 V vs Ag/AgCl. This is much more positive than the ∼-2.0 V vs Ag/AgCl onset observed for irreversible reduction of glycosyl bromides in our experiments. Theoretical investigations were undertaken to explain the function of the catalyst. Outer sphere electron transfer from a chromophore to substrate was discounted based on thermodynamics and electron transfer barriers determined by Marcus theory and non-equilibrium solvation calculations. Unactivated and activated chromophores were found to disproportionate to Cu(0) and Cu(II) species. The resulting Cu(0) species undergoes oxidative addition with a glycosyl bromide generating a Cu(II) species. Addition of a nucleophilic alcohol and oxidation of the Cu(II) species to Cu(III) result in rapid reductive elimination forming products and resetting the catalytic cycle.

NaBH3CN and other systems as substitutes of tin and silicon hydrides in the light or heat-initiated reduction of halosugars: a tunable access to either 2-deoxy sugars or 1,5-anhydro-itols

UV light-promoted reduction of acetobromoglucose by NaBH3CN in t-BuOH afforded 1,3,4,6-tetra-O-acetyl-2-deoxy-α-d-arabino-hexopyranose in high yield and purity, via a Surzur–Tanner rearrangement, while, with 10 mol % thiophenol added, acetylated 1,5-anhydro-d-glucitol was cleanly obtained. Such tin-free and mild reductions, presumed to proceed via radical pathways, were more efficient with NaBH3CN compared to NaBH4 or NaBD4, and do not occur with acetochloroglucose. Similar reductions to 1,3,4,6-tetra-O-acetyl-2-deoxy-α-d-arabino-hexopyranose were achieved upon heating to 80 °C t-BuOH or CH3CN solutions of NaBH3CN and AIBN, but with a lower selectivity due to competing ionic reactions. With other pyranosyl bromides, reductions by NaBH3CN could be tuned similarly (d-galacto), but some (d-manno, 5-thio-d-xylo) gave mainly or exclusively 1,5-anhydro-itols. Other conditions, or reagents promoting SET process, afforded also reduced products, but with lower rates or selectivities. Primary iodides were reduced readily with NaBH3CN under UV light.

Synthesis and In Vitro Antiviral Evaluation of Novel 1-Arylpyrazoles and Their N- and S-Glycosides

A series of 1-arylpyrazole and their N- and S- glycosides has been synthesized. The key step is the synthesis of 3- (furan-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde 1 via Vilsmeier -Haack reaction on the hydrazone of 2-acetylfuran. Compound 1 was transformed to N,N-dialkyl acrylamide (and/or acetamide) derivatives 3a, 3b and 6 through reaction with malonic acid and application of Willgerodt-Kindler reaction followed by reaction with dialkylamine. Moreover, the aglycons 5-[3-(furan-2-yl)-1-phenyl-1H-pyrazol-4-yl]-1,3,4-oxadiazole-2(3H)-thione 10 and 6-(furan-2-yl)-4-[3-(furan-2- yl) -1-phenyl-1H-pyrazol-4-yl]-2-oxo -1,2-dihydro-pyridine-3-carbonitrile 14b were prepared and coupled with 2,3,4,6- tetra-O-acetyl-α-D-gluco pyranosyl bromide under basic conditions to yield S-and N-glycoside derivatives 12 and 15, respectively. All the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectral studies. Antiviral activity was shown for most of the synthesized compounds. Compounds 4 and 14b exhibited a promising antiviral activity against vesicular stomatitis virus (VSV). Keywords: Antiviral Activity, Cytotoxicity, N-Nucleosides, Oxadiazoles, Pyrazoles, Thioglycosides, anticoagulant activity, S- Glycosides, 1H NMR, N- Glycosides, t vesicular stomatitis virus (VSV)., β-substituted acrylic acid, N, N- dimethylacetamide derivative, Acetamide, Esterification, hydrazinolysis

Synthesis of Andrographolide Glucopyranoside and Selective Cleavage of O‐acetyl Groups in Sugar Moiety

AbstractAndrographolide glucopyranosides were synthesized from andrographolide and tetra‐O‐acetyl‐β‐D‐gluco‐ pyranosyl bromide via a Koenigs‐Knorr reaction and deacetylation with a moderate deacetylation reagent dibutyltin oxide in methanol for the first time. The structures of the andrographolide derivatives were confirmed by IR, NMR, and HRMS. Deprotection of the acetylated andrographolide glucopyranoside with dibutyltin oxide in methanol selectively removed all acetyl groups of the sugar moiety, whereas the acetyl group of the andrographolide part and the base‐ or acid‐sensitive functional groups were retained.

SULFUR GLYCOSYLATION REACTIONS INVOLVING 3-ALLYL-2-THIOHYDANTOIN NUCLEOSIDE BASES AS POTENTIAL ANTIVIRAL AND ANTITUMOR AGENTS

3-Allyl-5-(Z)-arylidene-2-thiohydantoins 8a-f were synthesized from the direct condensation of the aromatic aldehydes 7a–f with 3-allyl-2-thiohydantoin (6), which in turn was prepared from the reaction of glycine and allyl isothiocyanate. The alkylation of 8a–f with alkyl bromides 9a, b gave 3allyl-5-(Z)-arylidene-2-(alkylmercapto)hydantoins 1a–1, S-Glycosylation and S-ribosylation took place on the reaction of 8a–f with pyranosyl bromides 11a, b and furanosyl bromide (15) under anhydrous alkaline conditions. The S-nucleoside structure, and not that of the N-nucleoside isomer, has been selected for the products. This structure has been confirmed from a model study of the coupling of 8a with α-D-glucose pentaacetate (13) and α-D-ribose tetrabenzoate (16) under Lewis acid conditions. The compounds do not display any antiviral and antitumoral activity.

Lignin model glycosides: preparation and optical resolution

R. F. Helm, M. Toikka, K. Li and G. Brunow, J. Chem. Soc., Perkin Trans. 1, 1997, 533 DOI: 10.1039/A603786K

Conformational effects in 2‐deoxyglucopyranos‐1‐yl radicals

2-Unsubstituted and 2-substituted (fluoro, tosylamino, n-propyl) 3,4,6-tri-O-acetyl-2-deoxypyranosyl radicals are obtained by reaction of the corresponding pyranosyl bromides or phenylselenides with photolytically generated trimethyltin radicals in benzene solution. Analysis of the ESR hyperfine splittings reveals that the 2-deoxy-2-fluoroglucopyranosyl radical exists in a boat-like conformation at room temperature, whereas the others retain the 4C1 chair conformation of the starting material. The observed conformational effects are explained by a “quasi-homo-anomeric” frontier orbital interaction of the nx lone pair of the ring oxygen atom with the σ* MO of the β-C-O bond, in which the singly occupied p orbital at C-1 acts as a mediator for this 1,3-anomeric interaction.

ChemInform Abstract: Synthesis and Preliminary Evaluation of 2‐(F‐Alkyl)ethyl Glycosides, a Series of New F‐Alkylated Surfactants for in vivo Uses.

AbstractThe glycosides (V) ‐ (VII) mentioned in the title are synthesized in three steps from the corresponding pyranosyl bromides using the ortho ester method.

ChemInform Abstract: Synthesis of 1‐Thioglycosides in a Catalytic Two‐phase System.

AbstractAn improved preparation of the thioglycosides (III) involves a reaction of the 1,2‐cis‐gluco‐ (Ia) and ‐galacto‐ (Ib) pyranosyl bromides with the thiols (II) in a catalytic two‐phase system.

ChemInform Abstract: Darstellung von β‐D‐Olivosyl(1 → 3)‐D‐olivosiden aus Mithramycin.

AbstractDas 4‐OH‐freie Rhamnosid (I) wird benzyliert und anschließend zum 1,2‐Dibromderivat (II) umgesetzt.

Darstellung Von β-D-Olivosyl(1→3)-D-olivosiden Aus Mithramycin

Abstract The benzyl glycoside 4 obtained from 2-bromo-2-deoxy-α-0-quinovosyl bromide 1, readily accessible by the dibromomethyl methyl ether reaction of 2, is deformylated to give the monohydroxy compound 5 which is used in glycosidation reactions. Treatment of 3 with dibromomethyl methyl ether results in the formation of the labile β-furanosyl bromide 7 and the cyrstalline pyranosyl bromide 8 in a ratio of 1:2, both of which are further characterized by their methyl glycosides 10 and 11, respectively. Action of dibromomethyl methyl ether at room temperature on the benzyl ether 6, conventionally prepared from 3, is shown to proceed initially to the glycosyl bromide 9. Compound 9 is cleaved to the 4-formyl-blocked pyranosyl bromide 12, and only after prolonged reaction time gives the pyranosyl halide 8. The glycosidation of the glycosyl bromide 1 with benzyl-4–0-benzyl-α-D-olivoside 13 in the presence of silver carbonate and silicate is a sluggish reaction and gives rather low yields of the β-and the α, l-3-linked disaccharides 15 and 16 in the ratio 3–4:1. With silver triflate the yield is improved to the 61% and the ratio 6:1 in favour of 15. Further transformations lead to both the syrupy olivosyl olivosides 17. and 18. In a more favourable reaction sequence 1 is condensed with the alcohol component 5 and silver triflate as promoter and yields the crystalline β-(19) and the α, 1→3-linked disaccharides (20) in 92% and a ratio of 6.5: 1. By subsequent transformations the protected title tetradeoxy disaccharide 21 is obtained.

Reaction of acylated methyl arabinosides with hydrogen bromide

Treatment of methyl tri- O-acetyl-β- D-arabinopyranoside ( 1a) with hydrogen bromide in benzene or in acetic acid gave, in addition to the pyranosyl bromide ( 2a), a considerable proportion of tri- O-acetyl- D-arabinofuranosyl bromide ( 5). Similar treatment of methyl tri- O-benzoyl-β- D-arabinopyranoside ( 1b) gave a good yield of the pyranosyl bromide ( 2b); no furanoid derivative was formed. Ring contraction also took place when methyl 4- O-acetyl-2,3-di- O-benzoyl-β- D-arabinopyranoside ( 7) was treated with hydrogen bromide, whereas the isomeric 3- O-acetyl-2,4-di- O-benzoyl compound ( 12) gave the pyranosyl bromide 13 in high yield. Thus, methyl pyranosides with an O-acetyl group at C-4 undergo ring contraction on treatment with hydrogen bromide. The corresponding compounds with O-benzoyl groups at C-4 gave pyranosyl bromides only.

Reactions of acylated pentoses and acylated methyl pentosides with dibromomethyl methyl ether. Preparation of bromo-deoxy-pentoses

When acylated pentoses or acylated methyl pentosides are treated with dibromomethyl methyl ether and zinc bromide, acylated pentopyranosyl bromides are formed rapidly. In a further, slow reaction the pyranosyl bromides are converted into bromo-deoxy-pentosyl bromides, mostly with the bromo-substituent at C-2. Acetylated D-xylo-, D-arabino, and D-lyxo-pyranosyl bromides all yield 3,4-di-O-acetyl-2-bromo-2-deoxy-D-xylopyranosyl bromide, whereas tri-O-acetyl-D-ribopyranosyl bromide forms 3,4-di-O-acetyl-2-bromo-2-deoxy-D-arabino-pyranosyl bromide. The yields of 2-bromo-2-deoxy-products are low in the acetate series, but treatment of tri-O-benzoyl-D-xylopyranosyl bromide with dibromomethyl methyl ether gives a high yield of 2-bromo-2-deoxy-D-xylose derivatives.

Substituted cerebrosides : Part III. 1- O-(4- O-β- D-hexopyranosyl-β- D-glucopyranosyl)dihydroceramides

Condensation of 2,3,6,-tri- O-acetyl-α- D-glucopyranosyl bromide with 3- O-benzoyl- N-octadecanoyl- DL-dihydrosphingosine afforded the dihydrocerebroside derivative 3- O-benzoyl- N-octadecanoyl-1- O(2,3,6-tri- O-acetyl-β- Dglucopyranosyl- DL-dihydrosphingosine (5).Reaction of the same bromide with methanol, followed by p-toluenesulfonylation, gave a good yield of methyl 2,3,6-tri- O- p-tolysulfonyl-β- D-glucopyranoside (3). Dihydroceramide dihexosides that are β- D-(1→4)-linked were prepared by reaction of 5 with 2,3,4,5-tetra- O-acetyl-α- D-gluco (or galacto) pyranosyl bromide. The anomeric configuration of the interglycosidic linkage depended on the conditions of the reaction; under relatively mild conditions, β-cellobiosyldihydroceramide and β-lactosyldihydroceramide (“dihydrocytolipin H”) resulted.