68733-20-0Relevant academic research and scientific papers
Improved synthesis of 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-α-D- mannopyranose
Teodorovic, Peter,Slaettegard, Rikard,Oscarson, Stefan
, p. 2675 - 2676 (2005)
By improved (anhydrous) work-up conditions of a triflate displacement reaction, the yield in the preparation of the versatile synthetic intermediate 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-α-D-mannopyranose has been significantly enhanced. This important precursor is now available in three efficient steps from D-glucose.
Sweet Drugs for Bad Bugs: A Glycomimetic Strategy against the DC-SIGN-Mediated Dissemination of SARS-CoV-2
Abreu Mota, Tiago,Aliu, Butrint,Cattaneo, Ivan,Ciancaglini, Matias,Cramer, Jonathan,Ernst, Beat,Jakob, Roman P.,Jiang, Xiaohua,Klein, Sebastian,Lakkaichi, Adem,Maier, Timm,Rabbani, Said,Schwardt, Oliver,Zimmer, Gert
, p. 17465 - 17478 (2021/11/04)
The C-type lectin receptor DC-SIGN is a pattern recognition receptor expressed on macrophages and dendritic cells. It has been identified as a promiscuous entry receptor for many pathogens, including epidemic and pandemic viruses such as SARS-CoV-2, Ebola virus, and HIV-1. In the context of the recent SARS-CoV-2 pandemic, DC-SIGN-mediated virus dissemination and stimulation of innate immune responses has been implicated as a potential factor in the development of severe COVID-19. Inhibition of virus binding to DC-SIGN, thus, represents an attractive host-directed strategy to attenuate overshooting innate immune responses and prevent the progression of the disease. In this study, we report on the discovery of a new class of potent glycomimetic DC-SIGN antagonists from a focused library of triazole-based mannose analogues. Structure-based optimization of an initial screening hit yielded a glycomimetic ligand with a more than 100-fold improved binding affinity compared to methyl α-d-mannopyranoside. Analysis of binding thermodynamics revealed an enthalpy-driven improvement of binding affinity that was enabled by hydrophobic interactions with a loop region adjacent to the binding site and displacement of a conserved water molecule. The identified ligand was employed for the synthesis of multivalent glycopolymers that were able to inhibit SARS-CoV-2 spike glycoprotein binding to DC-SIGN-expressing cells, as well as DC-SIGN-mediated trans-infection of ACE2+ cells by SARS-CoV-2 spike protein-expressing viruses, in nanomolar concentrations. The identified glycomimetic ligands reported here open promising perspectives for the development of highly potent and fully selective DC-SIGN-targeted therapeutics for a broad spectrum of viral infections.
Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks
Alex, Catherine,Visansirikul, Satsawat,Zhang, Yongzhen,Yasomanee, Jagodige P.,Codee, Jeroen,Demchenko, Alexei V.
, (2020/01/03)
Reported herein is the synthesis of a number of building blocks of 2-amino-2-deoxy-D-mannose from common D-glucose precursors.
Enhancing Potency and Selectivity of a DC-SIGN Glycomimetic Ligand by Fragment-Based Design: Structural Basis
Medve, Laura,Achilli, Silvia,Guzman-Caldentey, Joan,Thépaut, Michel,Senaldi, Luca,Le Roy, Aline,Sattin, Sara,Ebel, Christine,Vivès, Corinne,Martin-Santamaria, Sonsoles,Bernardi, Anna,Fieschi, Franck
, p. 14659 - 14668 (2019/11/11)
Chemical modification of pseudo-dimannoside ligands guided by fragment-based design allowed for the exploitation of an ammonium-binding region in the vicinity of the mannose-binding site of DC-SIGN, leading to the synthesis of a glycomimetic antagonist (compound 16) of unprecedented affinity and selectivity against the related lectin langerin. Here, the computational design of pseudo-dimannoside derivatives as DC-SIGN ligands, their synthesis, their evaluation as DC-SIGN selective antagonists, the biophysical characterization of the DC-SIGN/16 complex, and the structural basis for the ligand activity are presented. On the way to the characterization of this ligand, an unusual bridging interaction within the crystals shed light on the plasticity and potential secondary binding sites within the DC-SIGN carbohydrate recognition domain.
Cu-free Sonogashira Type Cross-Coupling of 6-Halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl) Quinazolin-4(3H)-ones as Potential Antimicrobial Agents
Poudapally, Suresh,Gurram, Venkateshwarlu,Garlapati, Ramesh,Tulluri, Chiranjeevi,Addepally, Uma,Vidya,Sharma, Somesh,Sen, Subhabrata,Pottabathini, Narender
, p. 2272 - 2286 (2017/07/24)
C(sp)–C(sp2) bond formation via Sonogashira cross-coupling reactions on 6-halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-ones with appropriate alkynes was explored. Optimization of reaction conditions with various catalysts, ligands, bases, and solvents was conducted. The combination of PdCl2(MeCN)2 with X-Phos proved to be the best metal–ligand system for this conversion in the presence of triethylamine (Et3N) in tetrahydrofuran at room temperature for iodosubstrates, at 80°C for the bromosubstrates in 8?h, and also for the chlorosubstrates in 16?h. We also demonstrated synthesis of a successful diversity-oriented synthesis library of highly functionalized quinazolinones via Cu-free Sonogashira coupling of diverse aryl halides and azido-alkyne (“click”) ligation reactions with substituted azides. The library exhibited significant antimicrobial activity when screened against several microorganisms.
Chemoenzymatic synthesis of GDP-azidodeoxymannoses: Non-radioactive probes for mannosyltransferase activity
Marchesan, Silvia,Macmillan, Derek
supporting information; experimental part, p. 4321 - 4323 (2009/03/12)
GDP-2-, 3-, 4- or 6-azidomannoses can be successfully prepared from the corresponding azidomannose-1-phosphates and GTP using the enzyme GDP-Mannosepyrophosphorylase (GDP-ManPP) from Salmonella enterica and may serve as useful probes for mannosyltransferase activity. The Royal Society of Chemistry.
IMMUNOGENS FOR MENINGITIDIS-A VACCINES
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Page/Page column 33, (2008/06/13)
An oligosaccharide useful for a Meningitidis A vaccine contains a first mannose unit having a spacer in the alpha configuration at C-1, which spacer is capable of conjugating to a protein, and which is connected to a second mannose unit through a 1,6-linkage which connects C-6 of the first unit to C-1 of the second unit, wherein the 1,6-linkage comprises a phosphonate. Related methods of making such compounds, analogous compounds, or intermediates thereof are also disclosed.
A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-acetamido-2-deoxy-d-mannopyranosides
Popelová, Alena,Kefurt, Karel,Hlavá?ková, Martina,Moravcová, Jitka
, p. 161 - 166 (2007/10/03)
4-Nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α- and β-d-mannopyranosides were prepared from methyl 4,6-O-benzylidene-α-d- glucopyranoside and 1,3,4,6-tetra-O-acetyl-α-d-glucopyranose, respectively. Chemoselective reduction of both azides with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-α-d- and -β-d-mannopyranosides in higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation yielded 4-nitrophenyl 2-acetamido-2-deoxy-α-d- mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-β-d-mannopyranoside in 20% and 44% overall yields, respectively.
Synthesis of 4-nitrophenyl 2-acetamido-2-deoxy-β-D-mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside
Krist, Pavel,Kuzma, Marek,Pelyvas, Istvan F.,Simerska, Pavla,Kren, Vladimir
, p. 801 - 811 (2007/10/03)
The title compounds were synthesized by the selective reduction of the azido group in 4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-mannopyranoside (8) and 4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-mannopyranoside (11), and by subsequent acetylation. Compound 8 was prepared by opening of the epoxide ring in methyl 2,3-anhydro-4,6-O-benzylidene-α-D-glucopyranoside (1) with sodium azide, followed by inversion of the configuration at C-3 in the resulting altropyranoside and glycosidation with 4-nitrophenol.
Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation
Saxon, Eliana,Luchansky, Sarah J.,Hang, Howard C.,Yu, Chong,Lee, Sandy C.,Bertozzi, Carolyn R.
, p. 14893 - 14902 (2007/10/03)
The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. Here we investigate the conversion of a panel of azide-functionalized mannosamine and glucosamine derivatives into cell-surface sialosides. A key tool in this study is the Staudinger ligation, a highly selective reaction between modified triarylphosphines and azides that produces an amide-linked product. A preliminary study of the mechanism of this reaction, and refined conditions for its in vivo execution, are reported. The reaction provided a means to label the glycoconjugate-bound azidosugars with biochemical probes. Finally, we demonstrate that the cell-surface Staudinger ligation is compatible with hydrazone formation from metabolically introduced ketones. These two strategies provide a means to selectively modify cell-surface glycans with exogenous probes.
