- 2-Hydroxyimino-6-aza-pyrimidine nucleosides: Synthesis, DFT calculations, and antiviral evaluations
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The global public health concerns and economic impact caused by emerging outbreaks of RNA viruses call for the search for new direct acting antiviral agents. Herein, we describe the synthesis, DFT calculations, and antiviral evaluation of a series of novel 2-hydroxyimino-6-aza-pyrimidine ribonucleosides. DFT//B3LYP/6-311+G?? calculations of the tautomeric distributions of the 2-hydroxyimino nucleosides 7, 8, and 9 in aqueous environments indicate a predominance of the canonical 2-(E)-hydroxyimino structure, where the hydroxyl group points away from the sugar moiety. The conformer distributions of the latter geometrical isomers of 7, 8, and 9 support the formation of five membered rings via hydrogen bonding between the (E)-C2N-O-H moiety and N3-H of 7 and 8 and between (E)-C2N-O-H and N3 of 9, creating purine shaped nucleosides with the glycosidic linkage at the pyrimidine ring. The newly synthesized nucleosides were screened against an RNA viral panel, of which moderate antiviral activity was observed against Zika virus (ZIKV) and human respiratory syncytial virus (HRSV). 6-Aza-2-hydroxyimino-5-methyluridine derivative 18 showed activity against ZIKV (EC50 3.2 μM), while its peracetylated derivative 19 showed activity against HRSV (EC50 5.2 μM). The corresponding 4-thiono-2-hydroxyimino derivative 8 showed activity against HRSV (EC50 6.1 μM) and against ZIKA (EC50 2.4 μM). This study shows that the 6-aza-2-hydroxyimino-5-methyluracil derived nucleosides can be further optimized to provide potent antiviral agents. This journal is
- Abou-Elkhair, Reham A. I.,Wasfy, Abdalla A.,Mao, Song,Du, Jinxi,Eladl, Sobhy,Metwally, Kamel,Hassan, Abdalla E. A.,Sheng, Jia
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p. 19650 - 19662
(2020/12/05)
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- Method for preparing 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose
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The invention relates to the field of organic synthesis, in particular to a method for preparing 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose, which comprises the following steps: mixing D-ribose with methanol and a catalyst, heating to react, neutralizing, and concentrating to obtain a methyl esterification intermediate III; mixing the methyl esterification intermediate III with an organic solvent, 4-dimethylaminopyridine and an acid-binding agent, cooling, dropwise adding benzoyl chloride for reaction, washing with water for layering, and drying to obtain a benzoylated intermediateII; finally, mixing the benzoylated intermediate II with an organic solvent and acetic anhydride, then adding a catalyst, stirring, carrying out heat preservation reaction for 10-20 hours at the temperature of 0-70 DEG C, and after the reaction is qualified, cooling, crystallizing and centrifuging to obtain a crude product; finally, performing recrystallization and centrifugal drying to obtain the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose, and obtaining the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-1-beta-D-ribofuranose. The method has the advantages of short reaction steps, high chemicaland optical purity, simple operation, easily available raw materials, low cost, small amount of three wastes, environmental friendliness and the like, and is suitable for industrial production.
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- Preparation of the tri-arabino di-mycolate fragment of mycobacterial arabinogalactan from defined synthetic mycolic acids
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An efficient synthetic approach to tri-arabino di-mycolates, using structurally defined synthetic α-, keto and methoxy mycolic acids is described.
- Mohammed, Mohsin O.,Al Dulayymi, Juma'a R.,Baird, Mark S.
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supporting information
p. 36 - 42
(2016/11/25)
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- Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry
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Derivatives of ribosyl pyrophosphate have been synthesized, and examined with magnesium salts in the coupling of the ribose unit to various nucleophiles, including pyrazole and 2-chloroimidazole. Only with the magnesium salt present did they generate the ribosyl cation by binding to the leaving group and then couple the ribose derivative with nucleophiles. The role of magnesium salts in phosphorylation of methanol by ATP was also examined. Here a remarkable effect was seen: phosphorylation by ATP was slowed with low concentrations of Mg2+ but accelerated by higher concentrations. Related effects were also seen in the effect of Mg2+ on phosphorylation by ADP. The likely mechanisms explain these effects.
- Gopinath, Purushothaman,Ramalingam, Vijayakumar,Breslow, Ronald
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p. 12011 - 12014
(2015/10/12)
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- Facile synthesis of β- And α-arabinofuranosides and application to cell wall motifs of M. tuberculosis
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Propargyl 1,2-orthoesters of arabinose are exploited for the synthesis of 1,2-trans furanosides; easily accessible 1,2-trans ribofuranosides are converted to challenging 1,2-cis-arabinofuranosides by oxidoreduction. Utility of these protocols was demonstrated by the successful synthesis of major structural motifs present in the cell surface of Mycobacterium tuberculosis. Key furanosylations were carried out under gold-catalyzed glycosidation conditions.
- Thadke, Shivaji A.,Mishra, Bijoyananda,Hotha, Srinivas
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supporting information
p. 2466 - 2469
(2013/06/27)
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- Automated solid phase synthesis of oligoarabinofuranosides
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Automated solid phase synthesis enables rapid access to the linear and branched arabinofuranoside oligosaccharides. A simple purification step is sufficient to provide the conjugation ready oligosaccharides in good yield.
- Kandasamy, Jeyakumar,Hurevich, Mattan,Seeberger, Peter H.
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supporting information
p. 4453 - 4455
(2013/06/26)
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- Ready preparation of furanosyl n-pentenyl orthoesters from corresponding methyl furanosides
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The 3,5-di-O-benzoyl n-pentenyl orthoesters of the four pentofuranoses have been prepared. The first key intermediate in each case is the methyl pentofuranoside(s), and a user-friendly procedure for the preparation of each, based on the Callam-Lowary precedent, is described, whereby formation of the crucial α/β anomeric mixture is optimized. The mixture is used directly to prepare the corresponding perbenzoylated pentofuranosyl bromide(s) and then the title compounds.
- Ramamurty, Changalvala V. S.,Ganney, Parimala,Rao, C. Srinivas,Fraser-Reid, Bert
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supporting information; experimental part
p. 2245 - 2247
(2011/05/17)
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- A one-pot synthesis of 1-α- and 1-β-d-arabinofuranosyl-2- nitroimidazoles: Synthons to the markers of tumor hypoxia
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1-α- and 1-β-D-Arabinofuranosyl-2-nitroimidazole (α-AZA and β-AZ A) are synthons for a number of potential markers of tissue hypoxia. A one pot synthesis in which 2-nitroimidazole is coupled with a mixture of α-and β-1-O-acetyl-2,3,5-tri-O-benzoyl-D-arabi
- Naimi, Ebrahim,Kumar, Piyush,McEwan, Alexander J. B.,Wiebe, Leonard I.
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p. 173 - 178
(2007/10/03)
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- Synthesis and biological evaluation of novel apio nucleosides with thiazole-4-carboxamide and 1,2,4-triazole-3-carboxamide
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In view of biological activities of azole nucleosides and apio-dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3-O-isopropylidene-apio-β -D-furanose (3), which was prepared from D-mannose.
- Kim, Myong Jung,Jeong, Lak Shin,Kim, Joong Hyup,Shin, Ji Hye,Chung, Soon Yong,Lee, Sang Kook,Chun, Moon Woo
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p. 715 - 724
(2007/10/03)
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- Synthesis and antiviral properties of arabino and ribonucleosides of 1,3-dideazaadenine, 4-nitro-1,3-dideazapurine and diketopiperazine
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Different arabinosides and ribosides, viz. Ara-DDA or 9(1-β-D- arabinofuranosyl) 1,3-dideazaadenine (6), Ara-NDDP or 9(1-β-D- arabinofuranosyl) 4-nitro-1,3-dideazapurine (7), Ara-DKP or 1(1-β-D- arabinofuranosyl) diketopiperazine (8), Ribo-DDA or 9(1-β-D-
- Sinha, Sarika,Srivastava, Richa,De Clercq, Erik,Singh, Ramendra K.
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p. 1815 - 1824
(2007/10/03)
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- The synthesis and radiolabeling of novel markers of tissue hypoxia of the iodinated azomycin nucleoside class
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Seven second-generation hypoxic markers of the iodinated azomycin nucleoside class have been synthesized and tested for hypoxia marking activity with tumor cells in vitro and in vivo. β-D-lodoazomycin galactoside (IAZG) and β-D-lodoazomycin xylopyranoside (IAZXP) demonstrated superior hypoxia marking properties relative to IAZA because of their higher water solubilities, rapid plasma clearance rates from tumor-bearing mice and maximum tumor/blood (T/B) and tumor/muscle (T/M) ratios. Our studies with animal tumor models show that T/B or T/M ratios of these markers determined by scintigraphy or planar imaging can predict for the relative degree of tumor hypoxia and for tumor radioresistance.
- Schneider,Engelhardt,Stobbe,Fenning,Chapman
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p. 541 - 557
(2007/10/03)
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- Synthesis of new 2 substituted 9-β-D-ribofuranosyl-8-azahypoxanthines. VII
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Title compounds were synthesized from the protected β-D-ribofuranosyl-1-azide 2, the sodium salt of cyanoacetamide and the suitable ester. The deblocked 8-azainosines were ineffective as inhibitors of Adenosine Deaminase.
- Biagi,Giorgi,Livi,Scartoni
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p. 525 - 536
(2007/10/02)
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- Arsenic-containing Ribosides from the Brown Alga Sargassum lacerifolium: X-Ray Molecular Structure of 2-Amino-3-propane-1-sulphonic Acid
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Three novel arsenic-containing ribosides, methyl 5-deoxy-5-(dimethylarsinoyl)-β-D-riboside, 1-O-mannitol, and a dimethylarsonio-β-D-riboside have been isolated from extracts of the brown alga Sargassum lacerifolium.In addition, five previously reported arsenic-containing ribosides, and some arsenate, were isolated from Sargassum, and dimethylarsinic acid was also shown to be present.The compounds were identified chiefly by NMR spectroscopy, and an X-ray molecular structure is reported for one of them, 2-amino-3-propane-1-sulphonic acid.The stereochemistry of the aglycones in these arsenic-containing ribosides is discussed and the configuration of 3--2-hydroxypropane-1-sulphonic acid 4 was assigned as 2S on the basis of a comparison of NMR spectra with those of synthetic model compounds.
- Francesconi, Kevin A.,Edmonds, John S.,Stick, Robert V.,Skelton, Brian W.,White, Allan H.
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p. 2707 - 2716
(2007/10/02)
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- Improved procedure for the regiospecific synthesis of 2'-deoxyribonucleosides
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2'-Deoxyribonucleosides are regiospecifically synthesized in high yields by catalyzing with KI-dibenzo-18-crown-6 PTC the condensation between unprotected silylated purines and pyrimidines and the appropriate easily available 2-deoxy-ribofuranosyl or pyranosyl sugar derivatives.
- Baud,Chavis,Lucas,Imbach
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p. 4437 - 4440
(2007/10/02)
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- REGIOSELECTIVE O-DEACYLATION OF FULLY ACYLATED GLYCOSIDES AND 1,2-O-ISOPORPYLIDENEALDOFURANOSE DERIVATIVES WITH HYDRAZINE HYDRATE
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On hydrazinolyis in 1:4 acetic acid-pyridine, and in pyridine, partisl O-deacylation of fully acylated methyl glycosides and some other glycosyl compounds ( 23 compounds ) was found to be induced, to give, in good yields, products bearing one free hydroxy
- Ishido, Yoshiharu,Sakairi, Nobuo,Sekiya, Masao,Nakazaki, Nobuo
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