Synthesis of fully protected ?-l-fucopyranosyl-(1?2)-?-d-galactopyranosides with a single free hydroxy group at position 2, 3 or 4 using O-(2-naphthyl)methyl (NAP) ether as a temporary protecting group

újratöltve - BIBFORM02025

Synthesis of a sulfonic acid mimetic of the sulfated Lewis A pentasaccharide

The first sulfonic acid mimetic of the sulfated Lewis A pentasaccharide in which the natural L-fucose unit is replaced by a D-arabinose ring was synthesized. Formation of the sulfonic acid moiety at a pentasaccharide level could be successfully achieved by means of introduction of an acetylthio moiety into the terminal D-galactose residue and subsequent oxidation. The equatorial arrangement of the acetylthio group linked to C-3 of the galactose ring could be obtained by double nucleophilic substitutions; efficient formation of the gulo-triflate derivatives required low-power microwave (MW) activation. Oxidation of the acetylthio group was carried out using Oxone in the presence of acetic aci

Large-scale synthesis of 6-deoxy-6-sulfonatomethyl glycosides and their application for novel synthesis of a heparinoid pentasaccharide trisulfonic acid of anticoagulant activity

Multigram-scale syntheses of three 6-deoxy-6-sulfonatomethyl a-glucosides were accomplished viareactions of the corresponding primary triflate derivatives with the lithiated ethyl methanesulfonate.Chemoselective glycosylation reactions of different 6-C-sulfonatomethyl glucoside donors were studied.The sulfonic acid-containing building blocks were utilised in a novel [2+3] block synthesis of a trisulfonicacid isoster of the anticoagulant pentasaccharide idraparinu

SYNTHESIS OF AN IDRAPARINUX ANALOGUE PENTASACCHARIDE MONOSULFONIC ACID

Heparin is a linear, highly sulfated polysaccharide that has been used clinically as an antithrombotic agent since 1940s. For its anticoagulant effect a pentasaccharide fragment (DEFGH pentasaccharide) is responsible. Heparin interacts with antithrombin, a serine protease inhibitor that blocks thrombin and factor Xa in the coagulation cascade. Our research group has been dealing with the synthesis of sulfonic acid analogues of the anticoagulant pentasaccharide domain of heparin. Longer duration of action and increased activity of the molecules are expected by exchanging the primary sulfate esters to bioisosteric sodium-sulfonatomethyl moieties

Application of Carbohydrates with Methylene or Vinyl Groups in Heck–Mizoroki Cross-Coupling Reactions with O-Heterocycles

Structurally novel carbohydrate–O-heterocycle derivatives linked by various unsaturated carbon bridges were synthesized by palladium-catalyzed cross-coupling reactions

Synthesis of α- -Fucopyranoside-Presenting Glycoclusters and Investigation of Their Interaction with Lectin (PHL)

Photorhabdus asymbiotica is gram-negative bioluminescent bacteria that is not only as effective an insect pathogen as other members of the genus, but also a bacterium that causes serious diseases in humans. The recently identified bangle 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, alpha-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 -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 alpha-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

Tricyclanos: conformationally constrained nucleoside analogues with a new heterotricycle obtained from a D-ribofuranose unit

A novel type of nucleoside analogue in which the sugar part is replaced by a new tricycle, 3,7,10-trioxa-11-azatricyclo[5.3.1.05,11]undecane has been prepared by substrate-controlled asymmetric synthesis. 1,5-Dialdehydes obtained from properly protected or unprotected uridine, ribothymidine, cytidine, inosine, adenosine and guanosine by metaperiodate oxidation reacted readily with tris(hydroxymethyl)aminomethane to provide the corresponding tricyclic derivatives with three new stereogenic centers. Through a double cyclisation cascade process the tricyclic compounds were obtained in good to high yields, with very high diastereoselectivity. Formation of one stereoisomer, out of the eight possible, was observed in all cases. The absolute configuration of the new stereotriad-containing tricyclic systems was aided by conventional NMR experiments followed by chemical shift calculations using an X-ray crystal structure as reference that was in good agreement with H–H distances obtained from a new ROESY NMR method. The synthesis was compatible with silyl, trityl and dimethoxytrityl protecting groups. A new reagent mixture containing ZnCl2, Et3SiH and hexafluoroisopropanol was developed for detritylation of the acid-sensitive tricyclano nucleosides

Stereoselective Synthesis of Carbon-Sulfur-Bridged Glycomimetics by Photoinitiated Thiol-Ene Coupling Reactions

Oligosaccharidesandglycoconjugatesareabundantinalllivingorganisms,takingpartina multitude of biological processes. The application of natural O-glycosides in biological studies and drugdevelopmentislimitedbytheirsensitivitytoenzymatichydrolysis. Thisissuemadeitnecessary to design hydrolytically stable carbohydrate mimetics, where sulfur, carbon, or longer interglycosidic connections comprising two or three atoms replace the glycosidic oxygen. However, the formation of the interglycosidic linkages between the sugar residues in high diastereoslectivity poses a major challenge. Here, we report on stereoselective synthesis of carbon-sulfur-bridged disaccharide mimetics by the free radical addition of carbohydrate thiols onto the exo-cyclic double bond of unsaturated sugars. A systematic study on UV-light initiated radical mediated hydrothiolation reactions of enoses bearing an exocyclic double bond at C1, C2, C3, C4, C5, and C6 positions of the pyranosyl ring with various sugar thiols was performed. The effect of temperature and structural variations of the alkenes and thiols on the efficacy and stereoselectivity of the reactions was systematically studied and optimized. The reactions proceeded with high efficacy and, in most cases, with complete diastereoselectivity producing a broad array of disaccharide mimetics coupling through an equatorially oriented methylensulfide bridge.L