Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown
Published: Jan. 1, 2023
Language: Английский
Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(22), P. 7773 - 7801
Published: Jan. 1, 2023
The structural complexity of glycans poses a serious challenge in the chemical synthesis glycosides, oligosaccharides and glycoconjugates. Glycan complexity, determined by composition, connectivity, configuration far exceeds what nature achieves with nucleic acids proteins. Consequently, glycoside ranks among most complex tasks organic synthesis, despite involving only simple type bond-forming reaction. Here, we introduce fundamental principles bond formation summarize recent advances oligosaccharide synthesis.
Language: Английский
Citations
45
The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(3), P. 1618 - 1625
Published: Jan. 18, 2024
Minimal structural differences in the structure of glycosyl donors can have a tremendous impact on their reactivity and stereochemical outcome glycosylation reactions. Here, we used combination systematic reactions, characterization potential reactive intermediates, in-depth computational studies to study disparate behavior systems involving benzylidene glucosyl mannosyl donors. While these been studied extensively, no satisfactory explanations are available for observed between 3-
Language: Английский
Citations
11
Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Chemical 1,1'-glycosylation for the synthesis of non-reducing disaccharides is complicated by need to simultaneously control stereochemistry at two anomeric centers. While considerable progress has been made in α,α-disaccharides, assembly 1,1'-β,β- and 1,1'-β,α-linked sugars received comparatively less attention. Many naturally occurring their biologically active mimetics feature asymmetrically located functional groups different positions on pyranose rings, highlighting demand reliable stereoselective methods synthesize fully orthogonally protected 1,1'-conjugated suitable targeted functionalisation create important biomolecules. By exploiting specific electronic torsional effects imposed protecting both glycosyl donor lactol acceptor molecules, we achieved highly β,β- β,α-1,1'-glycosylation successfully synthesised a library β,α-linked diglucosamines. Our approach based premise that reactivity can greatly influence stereochemical outcome glycosylation reaction. We show tailored choice orthogonal alter preferences acceptors, stabilising conformations, group-driven modulation nucleophilicity useful tool achieve 1,1'-glycosidic bond formation. Structure-activity relationships have established number donor-lactol pairs, with focus optimizing facilitate 1,1'-β,α-glycosylation side enhance neighboring stereoselectivity side.
Language: Английский
Citations
0
Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 369 - 406
Published: Feb. 17, 2025
Stereoselective glycosylations are one of the most challenging tasks synthetic glycochemists. The protecting building blocks on glycosides contribute significantly in attaining required stereochemistry resulting glycosides. Strategic installation suitable groups C-2 position, vicinal to anomeric carbon, renders neighbouring group participation, whereas distal C-3, C-4, and C-6 positions often claimed exhibit remote participation with carbon. Neighbouring being widely studied help glycochemists design protocols for multistep synthesis complex oligosaccharides turn, standardise process glycosylation towards a particular stereochemical output. While has been quite effective achieving produced glycosides, exhibits comparatively less efficacy complete stereoselectivity reactions. Remote is still highly debated topic scientific community. However, implementing participating role reactions practised achieve better stereocontrol facilitate formation synthetically glycosidic linkages.
Language: Английский
Citations
0
Science Advances, Journal Year: 2025, Volume and Issue: 11(15)
Published: April 9, 2025
The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance pathogenic Campylobacter jejuni . capsular polysaccharides these bacteria, containing unique 6-deoxy-β- d - ido -heptopyranosyl or l glycero -β- residues, have emerged as attractive antigens. Expeditious assembly oligosaccharides derived from glycans is challenging β- -idopyranosidic linkages formidable to directly construct. Furthermore, whether synthetic C. could induce sufficient immunogenicity potential antigens remains unexplored. Here, we report a protocol for forming bonds using α- -6-deoxy- -heptopyranosyl, -idopyranosyl, and -/ -α- ortho -hexynylbenzoates glycosylating agents under gold(I) catalysis. To demonstrate versatility methods, concise synthesis conjugatable di-/tetra-/hexa-/octasaccharides, having backbone [→3)-6-deoxy-β- -heptopyranosyl-(1→4)-2-acetamido-2-deoxy-β- -glucopyranosyl-(1→], has been achieved. assessment glycoconjugates, prepared by conjugating synthesized cross-reactive material 197, reveals disaccharide O -antigen developing campylobacteriosis. This work should facilitate development infections.
Language: Английский
Citations
0
Handbook of experimental pharmacology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown
Published: May 8, 2025
The stereodirecting effect of various distal benzoyl esters on the anomeric selectivity in galactopyranosylations was investigated. It found that O-6 galactosyl donors phenyl thioglycoside type had a negligible influence selectivity. Instead, α-selective galactosylations were observed with 4-O-benzoyl, 3,4-di-O-benzoyl, and 4,6-di-O-benzoyl protected donors, highly electron-withdrawing p-nitrobenzoyl (pNO2Bz) protecting group providing most galactosylations. Furthermore, α-selectivity enhanced by replacing thiophenyl aglycon functionality reactive cyclohexyl functionality. These findings enabled successful synthesis biologically relevant α-d-Gal(1→4)Gal linkage. obtained results do not suggest participation as course for selectivities.
Language: Английский
Citations
0
Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(25), P. 14052 - 14063
Published: June 13, 2023
Zwitterionic polysaccharides (ZPSs) are exceptional carbohydrates, carrying both positively charged amine groups and negatively carboxylates, that can be loaded onto MHC-II molecules to activate T cells. It remains enigmatic, however, how these bind receptors, understand the structural features responsible for this "peptide-like" behavior, well-defined ZPS fragments required in sufficient quantity quality. We here present first total synthesis of
Language: Английский
Citations
8
Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown
Published: July 9, 2024
L-Idose thioglycosides are useful glycosyl donors for the construction of glycosaminoglycan oligosaccharides. When activated with NIS and catalytic TMSOTf in presence methanol, stereoselectivity O-glycosylation displays an intriguing dependence on reaction temperature, increased preference formation α-glycoside at higher temperatures. Using a combination vt-NMR spectroscopy DFT calculations, we show how simple mechanistic model, based competing reactions iodinated thioglycoside, can explain main features temperature dependence. In this selectivity high is attributed to differences among entropy energy terms pathways. Neighbouring-group participation (giving intermediate acyloxonium ion) plays increasingly dominant role as raised. The general kinetic regime may also apply more broadly other glycosylations that likewise favour temperature.
Language: Английский
Citations
2
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown
Published: June 13, 2024
Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)-mediated inflammation, including upregulation various transcription factors activation pro-inflammatory pathways important for surveillance. Dysfunction PRRs-mediated signaling has been implicated in autoimmune diseases, while overactivation PRRs-driven responses during can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure-based design develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one ubiquitous PRRs, Toll-like Receptor 4 (TLR4). Taking advantage an exo-anomeric conformation specific molecular shape synthetic nonreducing β,β-diglucosamine, which was investigated by NMR, we developed two sets lipid A mimicking glycolipids capable either potently activating innate inhibiting signaling. Stereoselective 1,1'-glycosylation towards fully orthogonally protected GlcNβ(1↔1')βGlcN followed stepwise assembly differently functionalised phosphorylated provided biologically active molecules that were evaluated their ability trigger inhibit cellular responses. Two LPS mimetics, identified potent TLR4-specific inducers intracellular pathways, serve vaccine adjuvant- immunotherapy candidates, anionic with TLR4-inhibitory potential hold therapeutic promise management chronic inflammation.
Language: Английский
Citations
2