The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations

Comegna, Daniela; Bedini, Emiliano; Nola, Annalida Di; Iadonisi, Alfonso; Parrilli, Michelangelo

doi:10.1016/j.carres.2007.02.009

Cited by 23 publications

(15 citation statements)

References 30 publications

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“…Glycosylation of diol 5 was firstly tested with 2,3,4-tri-O-benzyl ethyl thiofucoside 10 [46] at different temperatures ranging from −30 to 25 • C using N-iodosuccinimide (NIS)/TMSOTf as thioglycoside activator system and a 5:3 v/v CH 2 Cl 2 -DMF as α-stereodirecting solvent mixture [33,47], that also allowed to conduct the reaction under homogeneous conditions. Since 2,3,4-tri-O-benzyl fucosyl N-phenyl-trifluoroacetimidate 11 [48] is also known to act as an efficient glycosyl donor in fucosylations [49], glycosylation of diol 5 was performed also with this Fuc donor. Polysaccharide products 12-i-iv obtained by precipitation with suitable solvents from the crude glycosylation mixtures showed rather complex 1 H NMR spectra (Figurs S7-S10) that impeded any structural characterization.…”

Section: Semi-synthesis Of Fcssmentioning

confidence: 99%

A Study for the Access to a Semi-synthetic Regioisomer of Natural Fucosylated Chondroitin Sulfate with Fucosyl Branches on N-acetyl-Galactosamine Units

et al. 2019

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Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan found up to now exclusively in the body wall of sea cucumbers. It shows several interesting activities, with the anticoagulant and antithrombotic as the most attractive ones. Its different mechanism of action on the blood coagulation cascade with respect to heparin and the retention of its activity by oral administration make fCS a very promising anticoagulant drug candidate for heparin replacement. Nonetheless, its typically heterogeneous structure, the detection of some adverse effects and the preference for new drugs not sourced from animal tissues, explain how mandatory is to open an access to safer and less heterogeneous non-natural fCS species. Here we contribute to this aim by investigating a suitable chemical strategy to obtain a regioisomer of the natural fCS polysaccharide, with sulfated l-fucosyl branches placed at position O-6 of N-acetyl-d-galactosamine (GalNAc) units instead of O-3 of d-glucuronic acid (GlcA) ones, as in natural fCSs. This strategy is based on the structural modification of a microbial sourced chondroitin polysaccharide by regioselective insertion of fucosyl branches and sulfate groups on its polymeric structure. A preliminary in vitro evaluation of the anticoagulant activity of three of such semi-synthetic fCS analogues is also reported.been the most intensely studied in the last two decades. It attracted a constantly increasing interest for its activity in biological events related to inflammation, hyperglycemia, atherosclerosis, cellular growth, cancer metastasis, angiogenesis, and, above all, coagulation and thrombosis [2]. The anticoagulant and antithrombotic activity is observed also on antithrombin (AT) and heparin cofactor II (HC-II)-free plasmas, for which the most widespread and long-term used anticoagulant drug-unfractionated heparin-is inactive, due to some differences in the mechanism of action of fCS on the blood coagulation cascade [3,4]. Furthermore, oral administration of fCS retains its activity, because it is digested neither during its adsorption in the gastrointestinal tract nor by intestinal bacterial enzymes [5]. These features make fCS a very promising anticoagulant drug candidate for heparin replacement [6].From a structural point of view, fCS shares the same linear core backbone as chondroitin sulfate (CS) polysaccharide, with alternating N-acetyl-d-galactosamine (GalNAc) and d-glucuronic acid (GlcA) residues linked together through alternating β-1→3 and β-1→4 glycosidic bonds and sulfated to a different extent on their hydroxyls. The unique structural peculiarity of fCSs is the additional presence of variously sulfated fucose (Fuc) branches [7,8], which are essential for the observed biological activities [9][10][11]. Very often the branches are constituted of a single Fuc unit α-glycosidically linked at O-3 site of GlcA residues. Nonetheless, fCSs from some sea cucumbers species with slightly different structural features have also been found [12]. Indeed, Ludwigothurea grisea [13], Eupentacta f...

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Section: Semi-synthesis Of Fcssmentioning

confidence: 99%

A Study for the Access to a Semi-synthetic Regioisomer of Natural Fucosylated Chondroitin Sulfate with Fucosyl Branches on N-acetyl-Galactosamine Units

et al. 2019

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“…Attempts to synthesize trisaccharide 3 : With thioglucoside 6 and L ‐colitose N ‐trifluorophenylacetimidate 5 in hand, we attempted the synthesis of trisaccharide 3 (Scheme ). Owing to the high reactivity of deoxysugars,16 the reaction was performed at −50 °C with 1.25 equivalents of glycosylating agent 5 per nucleophile. After 1 h, the target trisaccharide was mainly observed, along with deletion sequences.…”

Section: Resultsmentioning

confidence: 99%

“…Following Dess-Martin oxidation, [14] aldehyde 18 was converted into the corresponding hemiacetal by removal of the Nap ether protecting group with DDQ. This time, we opted to convert the colitose hemiacetal into N-trifluorophenylacetimidate [15] 5, which is an attractive alternative to the previously synthesized colitose trichloroacetimidate, owing to its more moderate reactivity [16] and its lower tendency to undergo O!N isoamide-to-amide rearrangement at the anomeric center.…”

Section: Synthesis Of the Building Blocksmentioning

confidence: 99%

“…Owing to the high reactivity of deoxysugars, [16] the reaction was performed at À50 8C with 1.25 equivalents of glycosyla-A C H T U N G T R E N N U N G ting agent 5 per nucleophile. Owing to the high reactivity of deoxysugars, [16] the reaction was performed at À50 8C with 1.25 equivalents of glycosyla-A C H T U N G T R E N N U N G ting agent 5 per nucleophile.…”

Section: Introductionmentioning

confidence: 99%

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Total Synthesis of theEscherichia coliO111O‐Specific Polysaccharide Repeating Unit

Calin

Eller

Hahm

et al. 2013

Chemistry A European J

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The first total synthesis of the O-antigen pentasaccharide repeating unit from Gram-negative bacteria Escherichia coli O111 was achieved starting from four monosaccharide building blocks. Key to the synthetic approach was a bis-glycosylation reaction to combine trisaccharide 10 and colitose 5. The colitose building block (5) was obtained de novo from non-carbohydrate precursors. The pentasaccharide was equipped at the reducing end with an amino spacer to provide a handle for subsequent conjugation to a carrier protein in anticipation of immunological studies.

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“…Thus, 21 was subjected to Zemplén deacetylation followed by hydrolysis of the Kdo methyl ester group to furnish the 4′-azido-4′-deoxy-disaccharide derivative 22 in 95 % yield, which was purified by chromatography on BioGel P2. The reduction of the azido group of 22 was accomplished by treatment with dithiothreitol (DTT)26 in aqueous pyridine/diisopropylamine, which left the allyl group intact and provided the 4′-amino-4′-deoxy- l -arabinopyranosyl derivative 23 . Purification was performed by ion-exchange chromatography on Dowex WX50 (H + form) eluted with 1 M aqueous NH 3 followed by desalting on BioGel P2 to give the β- l -Ara4N-(1→8)-Kdo allyl glycoside as the ammonium salt 23 in 60 % yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Neoglycoconjugates Containing 4‐Amino‐4‐deoxy‐L‐arabinose Epitopes Corresponding to the Inner Core of Burkholderia and Proteus Lipopolysaccharides

et al. 2011

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Disaccharides that contain 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and d-glycero-d-talo-oct-2-ulosonic acid (Ko) substituted at the 8-position by 4-amino-4-deoxy-β-l-arabinopyranosyl (Ara4N) residues have been prepared. Coupling an N-phenyltrifluoroacetimidate-4-azido-4-deoxy-l-arabinosylglycosyl donor to acetyl-protected allyl glycosides of Kdo and Ko afforded anomeric mixtures of disaccharide products in 74 and 90 % yield, respectively, which were separated by chromatography. Further extension of an intermediate Ara4N-(1→8)-Kdo disaccharide acceptor, which capitalized on a regioselective glycosylation with a Kdo bromide donor under Helferich conditions, afforded the branched trisaccharide α-Kdo-(2→4)[β-l-Ara4N-(1→8)]-α-Kdo derivative. Deprotection of the protected di- and trisaccharide allyl glycosides was accomplished by TiCl4-promoted benzyl ether cleavage followed by the removal of ester groups and reduction of the azido group with thiol or Staudinger reagents, respectively. The reaction of the anomeric allyl group with 1,3-propanedithiol under radical conditions afforded the thioether-bridged spacer glycosides, which were efficiently coupled to maleimide-activated bovine serum albumin. The neoglycoconjugates serve as immunoreagents with specificity for inner core epitopes of Burkholderia and Proteus lipopolysaccharides.

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The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations

Cited by 23 publications

References 30 publications

A Study for the Access to a Semi-synthetic Regioisomer of Natural Fucosylated Chondroitin Sulfate with Fucosyl Branches on N-acetyl-Galactosamine Units

A Study for the Access to a Semi-synthetic Regioisomer of Natural Fucosylated Chondroitin Sulfate with Fucosyl Branches on N-acetyl-Galactosamine Units

Total Synthesis of theEscherichia coliO111O‐Specific Polysaccharide Repeating Unit

Synthesis of Neoglycoconjugates Containing 4‐Amino‐4‐deoxy‐L‐arabinose Epitopes Corresponding to the Inner Core of Burkholderia and Proteus Lipopolysaccharides

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