Synthesis of neoglycoproteins containing L-glycero-α-D- manno-heptopyranosyl-(1→4)- and -(1→5)-linked 3-deoxy-α-D-manno-oct-2- ulopyranosylonic acid (Kdo) phosphate determinants

Sekljic, Harald; Wimmer, Norbert; Hofinger, Andreas; Brade, Helmut; Kosma, Paul

doi:10.1039/a700497d

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…To simplify deprotection at the final stages, both 2-amino-2-deoxy-groups were protected as N -acetyl derivatives keeping in mind difficulties encountered in several reported glycosylation reactions describing the formation of the respective imidates. 14 Although these unwanted reactions were known, the variety of protecting groups had to be limited in order to minimize loss of material in the multistep synthesis. The reducing terminus was equipped with an α-configured 3-aminopropyl spacer glycoside amenable to eventual coupling to proteins as well as suitable for conversion into the corresponding 3-azidopropyl derivatives to be used as substrate for ensuing “click”-chemistry.…”

Section: Resultsmentioning

confidence: 99%

“…The pentasaccharide was assembled starting from the β-(1 → 6)-linked diglucosamine backbone to be subsequently elongated by the Kdo residues. To simplify deprotection at the final stages, both 2-amino-2-deoxy-groups were protected as N -acetyl derivatives keeping in mind difficulties encountered in several reported glycosylation reactions describing the formation of the respective imidates . Although these unwanted reactions were known, the variety of protecting groups had to be limited in order to minimize loss of material in the multistep synthesis.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

et al. 2017

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The pentasaccharide fragment α-d-Man-(1 → 5)-[α-d-Kdo-(2 → 4)-]α-d-Kdo-(2 → 6)-β-d-GlcNAc-(1 → 6)-α-d-GlcNAc equipped with a 3-aminopropyl spacer moiety was prepared by a sequential assembly of monosaccharide building blocks. The glucosamine disaccharide—as a backbone surrogate of the bacterial lipid A region—was synthesized using an 1,3-oxazoline donor, which was followed by coupling with an isopropylidene-protected Kdo-fluoride donor to afford a protected tetrasaccharide intermediate. Eventually, an orthogonally protected manno-configured trichloroacetimidate donor was used to achieve the sterically demanding glycosylation of the 5-OH group of Kdo in good yield. The resulting pentasaccharide is suitably protected for further chain elongation at positions 3, 4, and 6 of the terminal mannose. Global deprotection afforded the target pentasaccharide to be used for the conversion into neoglycoconjugates and “clickable” ligands.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

et al. 2017

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“…This notorious side reaction of N -acetyl amino groups has been observed previously and is deemed responsible for the low reactivity of N -acetylated glycosyl acceptor derivatives in glycosylation reactions. 18,19…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the α-linked 3-azidopropyl spacer group most likely had sterically blocked the imidate formation at the reducing residue, and only a single imidate had been formed. This notorious side reaction of N -acetyl amino groups has been observed previously and is deemed responsible for the low reactivity of N -acetylated glycosyl acceptor derivatives in glycosylation reactions. , …”

Section: Resultsmentioning

confidence: 99%

Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike

et al. 2019

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Lipooligosaccharides (LOS) from the bacterium Rhizobium radiobacter Rv3 are structurally related to antigenic mammalian oligomannoses on the HIV-1 envelope glycoprotein spike that are targets for broadly neutralizing antibodies. Here, we prepared a hybrid structure of viral and bacterial epitopes as part of a vaccine design strategy to elicit oligomannose-specific HIV-neutralizing antibodies using glycoconjugates based on the Rv3 LOS structure. Starting from a Kdo2GlcNAc2 tetrasaccharide precursor, a central orthogonally protected mannose trichloroacetimidate donor was coupled to OH-5 of the innermost Kdo residue. To assemble larger glycans, the N-acetylamino groups of the glucosamine units were converted to imides to prevent formation of unwanted imidate byproducts. Blockwise coupling of the pentasaccharide acceptor with an α-(1→2)-linked mannotriosyl trichloroacetimidate donor introduced the D1-arm fragment. Glycosylation of O-6 of the central branching mannose with an α-(1→2)-α-(1→6)-linked mannotriosyl trichloroacetimidate donor unit then furnished the undecasaccharide harboring a D3-arm extension. Global deprotection yielded the 3-aminopropyl ligand, which was activated as an isothiocyanate or adipic acid succinimidoyl ester and conjugated to CRM197. However, representative oligomannose-specific HIV-neutralizing antibodies bound the undecasaccharide conjugates poorly. Possible reasons for this outcome are discussed herein along with paths for improvement.

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“…The trichloroacetimidates of D-glucofuranose [59], D-mannofuranose [59], and D-galactofuranose [59, 601 have been prepared and used for the synthesis of furanosyl glycosides. With the heptosyl trichloroacetimidate some neoglycoconjugates containing Hep( 1 -4)Kdo and Hep( 1 -5)Kdo-4-phosphate-(2-6)GlcNAc residues were synthesized which are part of the inner core region of bacterial lipopolysaccharides [61]. A 5-thio-~-fucosyl trichloroacetimidate was used for the synthesis of 5-S-~-Fuca( 1-2)Gal and other disaccharides which have inhibitory activity against a-L-fucosidases [ 621.…”

Section: Miscellaneous Compoundsmentioning

confidence: 99%

Trichloroacetimidates

Schmidt¹,

Jung²

2000

Carbohydrates in Chemistry and Biology

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Synthesis of neoglycoproteins containing L-glycero-α-D- manno-heptopyranosyl-(1→4)- and -(1→5)-linked 3-deoxy-α-D-manno-oct-2- ulopyranosylonic acid (Kdo) phosphate determinants

Cited by 8 publications

References 22 publications

Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of Rhizobial and Agrobacterial Lipopolysaccharides

Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike

Trichloroacetimidates

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