- Anomalous interaction of tri-acyl ester derivatives of uridine nucleoside with a l-α-dimyristoylphosphatidylcholine biomembrane model: a differential scanning calorimetry study
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Objectives: Uridine was conjugated with fatty acids to improve the drug lipophilicity and the interaction with phospholipid bilayers. Methods: The esterification reaction using carbodiimides compounds as coupling agents and a nucleophilic catalyst allowed us to synthesize tri-acyl ester derivatives of uridine with fatty acids. Analysis of molecular interactions between these tri-acyl ester derivatives and l-α-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV) – as a mammalian cell membrane model – have been performed by differential scanning calorimetry (DSC). Key findings: The DSC thermograms suggest that nucleoside and uridine triacetate softly interact with phospholipidic multilamellar vesicles which are predominantly located between the polar phase, whereas the tri-acyl ester derivatives with fatty acids (myristic and stearic acids) present a strongly interaction with the DMPC bilayer due to the nucleoside and aliphatic chains parts which are oriented towards the polar and lipophilic phases of the phospholipidic bilayer, respectively. However, the effects caused by the tri-myristoyl uridine and tri-stearoyl uridine are different. Conclusions: We show how the structural changes of uridine modulate the calorimetric behaviour of DMPC shedding light on their affinity with the phospholipidic biomembrane model.
- Berrío Escobar, Jhon Fernando,Márquez Fernández, Diana Margarita,Giordani, Cristiano,Castelli, Francesco,Sarpietro, Maria Grazia
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Read Online
- NMR studies show monomeric 5-fluorouridine forms base pairs of increased stability compared with uridine in non-aqueous solvents
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The binding constants and geometries for nucleoside base pairs involving 5-fluorouridine (FUr) and adenosine were determined by 1H, 13C, and 19F NMR to better understand how FUr may perturb RNA structure. 5FU:A base pairs are more stable than U:A base pairs.
- Gmeiner,Anderson,Sahasrabudhe
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Read Online
- Chemoenzymatic synthesis of Park's nucleotide: toward the development of high-throughput screening for MraY inhibitors
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An efficient chemoenzymatic synthesis of UDP-N-acetylmuramyl-l-alanyl-γ-d-glutamyl-meso-diaminopimelyl-d-alanyl-d-alanine (Park's nucleotide) is reported. UDP-MurNAc is efficiently synthesized by a minimum number of protecting strategies. One-pot amino ac
- Kurosu, Michio,Mahapatra, Sebabrata,Narayanasamy, Prabagaran,Crick, Dean C.
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- Optimized synthesis of [3-15N]-labeled uridine phosphoramidites
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A short and high-yielding synthetic route to [3-15N]-labeled uridine phosphoramidite 1 (26% overall yield from uridine) has been developed. This will enable automated synthesis of isotopically labeled RNA strands and facilitate their use in str
- Baral, Bharat,Kumar, Pawan,Anderson, Brooke A.,?stergaard, Michael E.,Sharma, Pawan K.,Hrdlicka, Patrick J.
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- Cyclic sulfates as synthetic equivalents of α-epoxynucleosides
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A stable sulfate derivative of N-nitrouridine has been obtained for the first time; it shows synthetic advantages in relation to its α-epoxide counterpart. A new iodide-mediated denitration reaction is reported.
- Serra, Carme,Farras, Jaume,Vilarrasa, Jaume
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Read Online
- Anti-hepatitis B virus compound as well as preparation method and application thereof
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The invention provides an anti-hepatitis B virus compound and a preparation method and application thereof, the compound is 4-thiouridine isobutyrate, the molecular formula is C13H18N2O6S, and the structural formula is shown in the specification. The compound provided by the invention can effectively inhibit the activity of hepatitis B virus, can be used as a substitute drug for lamivudine and telbivudine, solves the problem of drug resistance of lamivudine and the like in the aspect of resisting hepatitis B virus, is high in drug effect, low in toxicity and low in price, and provides a direction for development of drugs for treating hepatitis B. In addition, the invention discloses a preparation method of the compound 4-thiouridine isobutyrate, and the preparation method is mild in condition, easy to synthesize and suitable for industrial production.
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Paragraph 0025-0028
(2021/06/22)
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- Transglycosylation in the Modification and Isotope Labeling of Pyrimidine Nucleosides
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Transglycosylation of pyrimidine nucleosides is demonstrated in a one-pot synthesis of uridine derivatives under microwave irradiation. Inductive activation of 2′,3′,5′-tri-O-acetyl uridine with a 5-nitro group produces a more-reactive glycosyl donor. Under optimized Vorbrüggen conditions, the 5-nitrouridine facilitates a reversible nucleobase exchange with a series of 5-substituted uracils. The protocol is also exemplified in a gram-scale reaction under thermal heating. The strategy provides easy access to isotopically labeled uridine.
- Gong, Yong,Chen, Lu,Zhang, Wei,Salter, Rhys
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supporting information
p. 5577 - 5581
(2020/07/24)
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- Concise synthesis and antibacterial evaluation of novel 3-(1,4-disubstituted-1,2,3-triazolyl)uridine nucleosides
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We report herein a simple and efficient synthesis of a new series of antibacterial uridine nucleosides. The strategy involved a sequential silylation/N-glycosylation/N-propargylation procedure of uracil 1 for preparing the dipolarophile 5 in good yield. A series of novel uridine-[1,2,3]triazole nucleosides 6a–j were efficiently synthesized via the copper-catalyzed azide–alkyne cycloaddition (CuAAC) from dipolarophile 5 with different selected azides. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvements were observed when reactions were carried out under sonication. Their antibacterial potential has been evaluated by means of a micro-dilution assay against either Gram-positive or Gram-negative bacteria. Compounds 6i and 6j have shown significant bactericidal activity against Staphylococcus aureus (MIC = 10 and 6 μM, respectively), and 6h against Escherichia coli (MIC = 8 μM). Moreover, antibacterial kinetic assays showed that 6i and 6j significantly reduced the S. aureus growth rate at the MIC concentration, after 6 h, compared to their deprotected analogs, 6k and 6l, respectively. Compound 6h also significantly reduced the growth of E. coli. These antibacterial effects may be related to the penetrating properties of these compounds, as revealed by the leakage of nucleic acids from the sensitive strains.
- Tachallait, Hamza,Bouyahya, Abdelhakim,Talha, Aicha,Bakri, Youssef,Dakka, Nadia,Demange, Luc,Benhida, Rachid,Bougrin, Khalid
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- Stereoselective Synthesis of Highly Functionalized Arabinosyl Nucleosides through Application of an N-Nitro Protecting Group
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2′-Deoxy-2′,5-disubstituted arabinosyl uridine derivatives bearing a halogen (Cl, Br or I) at C2′ and an ethynyl group at C5 have been synthesized in 6 steps from 2′,3′,5′-tri-O-acetyl-5-iodo-uridine in overall yields of 61% (compound 3, Cl), 47% (compound 4, Br), and 19% (compound 5, I). Stabilization of a 2′-O-triflyl leaving group intermediate to overcome spontaneous intramolecular 2,2′-anhydro uridine formation was pivotal to the synthesis. Specifically, to favor SN2 reaction with a halogen nucleophile over intramolecular cyclization, the nucleophilicity of O-2 oxygen was reduced by incorporation of an adjacent electron withdrawing nitro substituent at N-3. The introduction of the 3-N-nitro group proceeded rapidly (nitronium trifluoroacetate, 1 min) and in quantitative yield. A one-pot method to remove the 3-N-nitro group by reductive nitration (zinc metal in acetic acid, 5 min) and the silyl protecting groups of the alkyne and 3′,5′ hydroxyls (fluoride reagent, 16 h) was established as the final synthetic step. This application of the 3-N-nitro protecting group addresses the significant shortfalls of the conventional approach to synthesis of 2′ modified nucleosides, wherein condensation of a 2′ modified sugar fragment with a pyrimidine base provides poor stereocontrol of N-glycosylation, low yields and incompatibility with 2′ iodo sugars.
- Hilko, David H.,Bornaghi, Laurent F.,Poulsen, Sally-Ann
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supporting information
p. 11944 - 11955
(2018/09/25)
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- Effective synthesis of nucleosides utilizing O-acetyl-glycosyl chlorides as glycosyl donors in the absence of catalyst: Mechanism revision and application to silyl-hilbert-johnson reaction
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An effective synthesis of nucleosides using glycosyl chlorides as glycosyl donors in the absence of Lewis acid has been developed. Glycosyl chlorides have been shown to be pivotal intermediates in the classical silyl-Hilbert-Johnson reaction. A possible mechanism that differs from the currently accepted mechanism advanced by Vorbrueggen has been proposed and verified by experiments. In practice, this catalyst-free method provides easy access to Capecitabine in high yield.
- Liang, Chengyuan,Ju, Weihui,Ding, Shunjun,Sun, Han,Mao, Gennian
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- Selective Acylation of Nucleosides, Nucleotides, and Glycerol-3-phosphocholine in Water
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A convenient selective synthesis of 2′,3′-di-O-acetyl-nucleotide-5′-phosphates, 2′,3′-di-O-acetyl-nucleotide-5′-triphosphates and 2′,3′,5′-tri-O-acetyl-nucleosides in water has been developed. Furthermore, a long-chain selective glycerol-3-phosphocholine diacylation is elucidated. These reactions are environmentally benign, rapid, high yielding, and the products are readily purified. Importantly, this reaction may indicate a prebiotically plausible reaction pathway for the selective acylation of key metabolites to facilitate their incorporation into protometabolism.
- Fernández-García, Christian,Powner, Matthew W.
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supporting information
p. 78 - 83
(2016/12/26)
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- Synthesis of 4-thio-5-(2′′-thienyl)uridine and cytotoxicity activity against colon cancer cells: In vitro
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A novel anti-tumor agent 4-thio-5-(2′′-thienyl)uridine (6) was synthesized and the in vitro cytotoxicity activity against mice colon cancer cells (MC-38) and human colon cancer cells (HT-29) was evaluated by MTT assay. The results showed that the novel compound had antiproliferative activity toward MC-38 and HT-29 cells in a dose-dependent manner. The cell cycle analysis by flow cytometry indicated that compound 6 exerted in tumor cell proliferation inhibition by arresting HT-29 cells in the G2/M phase. In addition, cell death detected by propidium iodide staining showed that compound 6 efficiently induced cell apoptosis in a concentration-dependent manner. Moreover, the sensitivity of human fibroblast cells to compound 6 was far lower than that of tumor cells, suggesting the specific anti-tumor effect of 4-thio-5-(2′′-thienyl)uridine. Taken together, novel compound 6 effectively inhibits colon cancer cell proliferation, and hence would have potential value in clinical application as an antitumor agent.
- Zhang, Xiaohui,Li, Depeng,Qin, Jianzhong,Xu, Yaozhong,Ma, Kedong
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p. 70099 - 70105
(2016/08/05)
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- Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products
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Background: The peracetylation is a simple chemical modification that can be used to enhance the bioavailability of hydrophilic products and to obtain safe and stable pro-drugs. Results: A totally green, solvent-free and catalyst-free microwave (MW)-assisted method for peracetylation of natural products such as oleuropein, alpha-hederin, quercetin and rutin is presented. By simply tuning the MW heating program, polyols with chemical diverse -OH groups or thermolabile functionalities can be peracetylated to improve the biological activity without degradation of the natural starting molecules. An evaluation of the process greenness was performed. Conclusion: The method is potentially universally applicable for green acetylation of hydrophilic biological molecules, potentially easily scalable for industrial applications, including pharmaceutical, cosmetic and food industry.
- Oliverio, Manuela,Costanzo, Paola,Nardi, Monica,Calandruccio, Carla,Salerno, Raffaele,Procopio, Antonio
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supporting information
p. 2222 - 2233
(2016/11/17)
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- NMR studies on 4-thio-5-furan-modified and 4-thio-5-thiophene-modified nucleosides
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Systematic NMR characterization of 4-thio-5-furan-pyrimidine nucleosides or 4-thio-5-thiophene-pyrimidine nucleosides (ribonucleosides and 2′-deoxynucleosides) was performed. All proton and carbon signals of 4-thio-5-thiophene-ribouridine and related analogues were unambiguously assigned. The orientations of the base (4-thiouridine or its deoxy analogue) relative to the ring (furan or thiophene) are explored by a NMR approach and further supported by X-ray crystallographic studies. The procedures presented here would be applicable to other modified nucleosides and nucleotides. Copyright
- Zhang, Xiao-Hui,Xu, Yao-Zhong
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p. 887 - 892
(2016/10/24)
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- Fluorescent nucleoside derivatives as a tool for the detection of concentrative nucleoside transporter activity using confocal microscopy and flow cytometry
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The abundance and function of transporter proteins at the plasma membrane are likely to be crucial in drug responsiveness. Functional detection of human concentrative nucleoside transporters (hCNTs) is of interest for predicting drug sensitivity because of their ability to transport most nucleoside-derived drugs. In the present study, two fluorescent nucleoside analogues, uridine-furan and etheno-cytidine, were evaluated as tools to study in vivo nucleoside transporter-related functions. These two molecules showed high affinity interactions with hCNT1 and hCNT3 and were shown to be substrates of both transporters. Both fluorescence microscopy and flow cytometry experiments showed that uridine-furan uptake was better suited for distinguishing cells that express hCNT1 or hCNT3. These data highlight the usefulness of fluorescent nucleoside derivatives, as long as they fulfill the requirements of confocal microscopy and flow cytometry, for in vivo analysis of hCNT-related function.
- Claudio-Montero, Ana,Pinilla-Macua, Itziar,Fernández-Calotti, Paula,Sancho-Mateo, Carlos,Lostao, Mar?a Pilar,Colomer, Dolors,Grandas, Anna,Pastor-Anglada, Mar?al
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p. 2158 - 2166
(2015/06/16)
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- ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF
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The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
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Page/Page column 625
(2016/06/15)
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- ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF
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The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
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Page/Page column 633
(2016/06/28)
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- Alternative nucleic acid molecules and uses thereof
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The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
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- A general method for N-glycosylation of nucleobases promoted by (p-Tol)2SO/Tf2O with thioglycoside as donor
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Based on a preactivation strategy using the (p-Tol)2SO/Tf2O system, a series of nucleosides were synthesized by coupling various thioglycosides with pyrimidines and purines under mild conditions. High yields and excellent β-stereoselectivities were obtained with either armed or disarmed N-glycosylation donors by tuning the amount of (p-Tol)2SO additive.
- Liu, Guang-Jian,Zhang, Xiao-Tai,Xing, Guo-Wen
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supporting information
p. 12803 - 12806
(2015/08/06)
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- MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF
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The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.
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Page/Page column 292
(2014/07/07)
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- In search of flavivirus inhibitors: Evaluation of different tritylated nucleoside analogues
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Following up on a hit that was identified in a large scale cell-based antiviral screening effort, a series of triphenylmethyl alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against the dengue virus (DENV) and the yellow fever virus (YFV). Hereto, trityl moieties were attached at various positions of the sugar ring combined with subtle variations of the heterocyclic base. Several triphenylmethyl modified nucleosides were uncovered being endowed with submicromolar in vitro antiviral activity against the YFV. The most selective inhibitor in this series was 3′,5′-bis-O-tritylated-5-chlorouridine (1b) affording a selectivity index of over 90, whereas the 3′,5′-bis-O-tritylated inosine congener (5b) displayed the highest activity, but proved more toxic. The finding of these lipophilic structures being endowed with high antiviral activity for flaviviruses, should stimulate the interest for further structureeactivity research.
- Chatelain, Grégory,Debing, Yannick,De Burghgraeve, Tine,Zmurko, Joanna,Saudi, Milind,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
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supporting information
p. 249 - 255
(2013/10/01)
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- A chemo-enzymatic approach to specifically click-modified RNA
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The growing interest in single-molecule analysis of RNA calls for programmable enzymatic labeling strategies beyond the horizon of solid-phase synthesized RNAs. Herein we describe an easy and versatile chemo-enzymatic approach to label RNA at its termini or defined internal positions via click-chemistry.
- Dojahn, Claudine M.,Hesse, Marlen,Arenz, Christoph
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p. 3128 - 3130
(2013/06/05)
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- Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides
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Unambiguous characterization of 5-substituted-4-thiopyrimidine nucleosides (ribonucleosides and 2'-deoxynucleosides) was performed using NMR spectroscopy. Assignments of all proton and carbon signals of 5-bromo-4-thiouridine and related nucleosides were systematically carried out and firmly established by COSY and HMQC techniques. The NMR data of various 4-thiopyrimidine nucleosides are compared, and the key contributing factors discussed. The approach presented here is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright
- Zhang, Xiaohui,Wang, Jian,Xu, Yao-Zhong
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p. 523 - 529
(2013/09/02)
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- Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation
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Five ribofuranosyl pyrimidine nucleosides and their corresponding 1,2,3-triazole derivatives have been synthesized and characterized. Their inhibitory action to Ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are potent competitive inhibitors of RNase A with low μM inhibition constant (Ki) values with the ones having a triazolo linker being more potent than the ones without. The most potent of these is 1-[(β-d-ribofuranosyl)-1,2,3-triazol-4-yl]uracil being with Ki = 1.6 μM. The high resolution X-ray crystal structures of the RNase A in complex with three most potent inhibitors of these inhibitors have shown that they bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B1 subsite while the triazole moiety binds at the main subsite P1, where P-O5′ bond cleavage occurs, and the ribose at the interface between subsites P1 and P0 exploiting interactions with residues from both subsites. The effect of a susbsituent group at the 5-pyrimidine position at the inhibitory potency has been also examined and results show that any addition at this position leads to a less efficient inhibitor. Comparative structural analysis of these RNase A complexes with other similar RNase A - ligand complexes reveals that the triazole moiety interactions with the protein form the structural basis of their increased potency. The insertion of a triazole linker between the pyrimidine base and the ribose forms the starting point for further improvement of these inhibitors in the quest for potent ribonucleolytic inhibitors with pharmaceutical potential.
- Parmenopoulou, Vanessa,Chatzileontiadou, Demetra S.M.,Manta, Stella,Bougiatioti, Stamatina,Maragozidis, Panagiotis,Gkaragkouni, Dimitra-Niki,Kaffesaki, Eleni,Kantsadi, Anastassia L.,Skamnaki, Vassiliki T.,Zographos, Spyridon E.,Zounpoulakis, Panagiotis,Balatsos, Nikolaos A.A.,Komiotis, Dimitris,Leonidas, Demetres D.
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p. 7184 - 7193
(2013/01/15)
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- An efficient synthetic approach to 6,5′-(S)- and 6,5′-(R)- cyclouridine
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Here we present new routes for the efficient syntheses of 6,5′-(S)- and 6,5′-(R)-cyclouridine. The syntheses utilize readily accessible uridine as a starting material. This route to the R diastereomer is significantly more efficient than previous synthetic efforts, allowing us to obtain large amounts of pure material for future biological testing.
- Theile, Christopher S.,McLaughlin, Larry W.
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supporting information; experimental part
p. 5587 - 5589
(2012/07/17)
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- Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus
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Uridine-based nucleoside analogues have often been found to have relatively poor antiviral activity. Enzymatic assays, evaluating inhibition of influenza virus RNA polymerase, revealed that some uridine triphosphate derivatives displayed inhibitory activity on UTP incorporation into viral RNA. Here we report the synthesis, antiviral activity and enzymatic evaluation of novel ProTides designed to deliver the activated (monophosphorylated) uridine analogues inside the influenza virus-infected cells. After evaluation of the activation profile we identified two ProTides with moderate antiviral activity in MDCK cells (23a, EC99=49±38μM and 23b, EC99≥81μM) while the corresponding nucleoside analogue (2'-fluoro-2'-deoxyuridine) was inactive. Thus, at least in these cases the poor antiviral activity of the uridine analogues may be ascribed to poor phosphorylation.
- Meneghesso, Silvia,Vanderlinden, Evelien,Stevaert, Annelies,McGuigan, Christopher,Balzarini, Jan,Naesens, Lieve
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scheme or table
p. 35 - 43
(2012/07/28)
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- Design, synthesis, and spectroscopic properties of extended and fused pyrrolo-dC and pyrrolo-C analogs
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The syntheses of four fluorescent nucleoside analogs, related to pyrrolo-C (PyC) and pyrrolo-dC (PydC) through the conjugation or fusion of a thiophene moiety, are described. A thorough photophysical analysis of the nucleosides, in comparison to PyC, is reported.
- Noé, Mary S.,Ríos, Andro C.,Tor, Yitzhak
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scheme or table
p. 3150 - 3153
(2012/09/22)
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- Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors
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A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y2, P2Y4, and P2Y6 receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y2 receptor. 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 μM at P2Y2 and >70-fold selectivity versus P2Y4 and P2Y 6 receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y4 agonist (EC50 4.98 μM, >20-fold selective vs P2Y2 and P2Y6). In contrast, replacement of the 2-keto function in UDP by NH yielded a potent P2Y2 agonist (12g, iso-CDP, EC50 = 0.604 μM, >100-fold selective). In an attempt to obtain metabolically stable UTP analogues, β,γ-dichloro- and β,γ-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y2, and in some cases also by P2Y6, than by P2Y4 receptors. 4-Thio-β,γ-difluoromethylene-UTP (14g) was a potent P2Y2 agonist with an EC50 value of 0.134 μM and >50-fold selectivity. N3-Phenacyl-β,γ-dichloromethylene- UTP (14b) proved to be a potent P2Y6 receptor agonist (EC 50 0.142 μM) with high selectivity versus P2Y4 (50-fold) and moderate selectivity versus P2Y2 receptors (6-fold).
- El-Tayeb, Ali,Qi, Aidong,Nicholas, Robert A.,Müller, Christa E.
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supporting information; experimental part
p. 2878 - 2890
(2011/06/24)
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- An efficient approach to the synthesis of nucleosides: Gold(I)-catalyzed N-glycosylation of pyrimidines and purines with glycosyl ortho-alkynyl benzoates
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Persuaded with gold: The title reaction in the presence of [Ph 3PAuNTf2] (Tf=trifluoromethanesulfonyl) led conveniently to the corresponding nucleosides with excellent regioselectivity (see scheme). Even purine derivatives underwent this transformation owing to the mild conditions, which enabled the use of protecting groups that would not usually be compatible with N-glycosylation conditions. Copyright
- Zhang, Qingju,Sun, Jiansong,Zhu, Yugen,Zhang, Fuyi,Yu, Biao
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supporting information; experimental part
p. 4933 - 4936
(2011/06/24)
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- A versatile synthesis of 5'-fenctionalized nucleosides through regioselective enzymatic hydrolysis of their peracetylated precursors
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We describe a chemo-enzymatic synthesis of modified nucleosides through lipase-catalyzed hydrolysis of their peracetylated precursors. It was found from screening of a large number of substrates that these enzymesregioselectivities were affected by the sugar and the nucleobase structures. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monodeprotecled purine and pyrimidine nucleosides useful as intermediates for the synthesis of high-value nucleosides and mononucleotides. By this approach, the chemo-enzymatic preparation of doxifluridine (14) and uridine 5'-monophosphate (5'-UMP, 15) from peracetylated uridine 1 was carried out. Elimination of many of the processing stages associated with existing methods was achieved, and higher yields and products of increased purity were generated. Wiley-VCH Verlag GmbH & Co. KGaA.
- Bavaro, Teodora,Rocchietti, Silvia,Ubiali,Filice, Marco,Terreni, Marco,Pregnolato, Massimo
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experimental part
p. 1967 - 1975
(2009/09/08)
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- Ionic liquid mediated synthesis of 5-halouracil nucleosides: Key precursors for potential antiviral drugs
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Synthesis of antiviral 5-halouracil nucleosides, also used as key precursors for the synthesis of other potential antiviral drugs, has been demonstrated using ionic liquids as convenient and efficient reaction medium.
- Kumar, Vineet,Malhotra, Sanjay V.
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experimental part
p. 821 - 834
(2010/08/20)
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- Effective synthesis of nucleosides with glycosyl trifluoroacetimidates as donors
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Glycosyl trifluoroacetimidates have been disclosed to be effective glycosyl donors for the synthesis of nucleosides; the present N-glycosylation protocol requires only a catalytic amount of TMSOTf as promoter and proceeds smoothly at room temperature.
- Liao, Jinxi,Sun, Jiansong,Yu, Biao
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p. 5036 - 5038
(2008/12/21)
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- Synthesis and solution conformation studies of the modified nucleoside N4,2′-O-dimethylcytidine (m4Cm) and its analogues
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The dimethylated ribosomal nucleoside m4Cm and its monomethylated analogues Cm and m4C were synthesized. The conformations (syn vs anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O vs N methylation) was found to have an effect on the sugar pucker of cytidine.
- Mahto, Santosh K.,Chow, Christine S.
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p. 8795 - 8800
(2008/12/23)
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- Fe2(SO4)3·xH2O-catalyzed per-O-acetylation of sugars compatible with acid-labile protecting groups adopted in carbohydrate chemistry
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Fully acetylated saccharides are inexpensive and very useful starting materials for the synthesis of many naturally occurring glycosides, oligosaccharides, and glycoconjugates. Ferric sulfate hydrate (Fe2(SO4)3·xH2O) was found to be a valuable Lewis acid promoter in the per-O-acetylation reaction of saccharides with acetic anhydride in 100% of conversion rate and 88-99% yields. Interestingly, the procedure is perfectly compatible with the presence of a variety of acid-labile protecting groups, such as isopropylidene, benzylidene, trityl, and TBDMS groups. The reactions were simply performed by stirring the mixture of a sugar with a slight excessive acetic anhydride in the presence of 2.0 mol % of Fe2(SO4)3·xH2O at rt and the pure products were obtained by a simple dilution of the reaction mixture with dichloromethane and washings with aqueous Na2CO3.
- Shi, Lei,Zhang, Guisheng,Pan, Feng
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p. 2572 - 2575
(2008/09/19)
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- Water gelation abilities of alkylbenzyltriazole-appended 2′-deoxyribonucleoside and ribonucleoside
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Effective hydrogelators based on alkylbenzyltriazole-appended 2′-deoxyribonucleioside and ribonucleoside nucleobase-modified uridine were prepared and the dependence of gelation properties on the nature of single hydroxyl group was investigated. The nucleosides were synthesized by modifying the position of the uracin base with alkylbenzyltriazole units. The small molecular-based gelators of organic and aqueous solvents were prepared from amino acids, bis-ureas, sugars, nucleic acid, and steroids. It was found that the balance between the hydrophilic and hydrophobic characteristics and the nature of the gelators' interactions proved to be an important factors for the small molecular hydrogelators. It was also found that the uridine-based hydrogelators exhibited gelation behavior different to that of corresponding 2-deoxyuridine based systems. The results show that they possess relatively higher minimum gelation concentrations (MGC).
- Park, Sun Min,Shen, Yongcun,Kim, Byeang Hyean
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p. 610 - 612
(2008/03/14)
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- Pyridine-free and solvent-free acetylation of nucleosides promoted by molecular sieves
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A practical method for the acetylation of purine and pyrimidine nucleosides employing a combination of acetic anhydride and potassium-exchanged molecular sieves is described. Besides the high yields obtained for the acylated nucleosides, the procedure is simple, inexpensive and environmentally benign, avoiding the use of pyridine or co-solvents as additives. Georg Thieme Verlag Stuttgart.
- Sá, Marcus Mandolesi,Meier, Lidiane
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p. 3474 - 3478
(2007/10/03)
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- Hydrothermal deamidation of 4-N-acylcytosine nucleoside derivatives: Efficient synthesis of uracil nucleoside esters
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(Chemical Equation Presented) N,O-Peracylated cytidine and 2′-deoxycytidine derivatives in superheated water/DME solutions (oil bath at 125°C) undergo hydrolytic deamidation (and/or N-deacylation). Acylated starting materials derived from arylcarboxylic acids give the corresponding uridine esters cleanly, and such derivatives crystallize selectively from the cooled reaction mixtures in high yields.
- Nowak, Ireneusz,Robins, Morris J.
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p. 4903 - 4905
(2007/10/03)
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- Nucleophilic acyl substitutions of anhydrides with protic nucleophiles catalyzed by amphoteric, oxomolybdenum species
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(Chemical Equation Presented) Among six different group VIb oxometallic species examined, dioxomolybdenum dichloride and oxomolybdenum tetrachloride were the most efficient catalysts to facilitate nucleophilic acyl substitution (NAS) of anhydrides with a myriad array of alcohols, amines, and thiols in high yields and high chemoselectivity. In contrast to the well-recognized redox chemical behaviors associated with oxomolybdenum(VI) species, the catalytic NAS was unprecedented and tolerates virtually all kinds of functional groups. By using benzoic anhydride as a mediator for in situ generation of an incipient mixed anhydride-MoO2Cl2 adduct with a given functional alkanoic acid, one can achieve oleate, dipeptide, diphenylmethyl, N-Fmoc-α-amino, pyruvic, and tert-butylthio ester, N-tert-butylamide, and trityl methacrylate syntheses with appropriate protic nucleophiles. The amphoteric character of the Mo=O unit in oxomolybdenum chlorides was found to be responsible for the catalytic NAS profile as supported by a control NAS reaction of using an authentic adduct-MoOCl2(O2-CBu t)2 between pivalic anhydride and MoO2Cl 2 as the catalyst.
- Chen, Chien-Tien,Kuo, Jen-Huang,Pawar, Vijay D.,Munot, Yogesh S.,Weng, Shieu-Shien,Ku, Cheng-Hsiu,Liu, Cheng-Yuan
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p. 1188 - 1197
(2007/10/03)
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- PYRIMIDINES, SUCH AS URIDINE, IN TREATMENTS FOR PATIENTS WITH BIPOLAR DISORDER
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The invention is based on the discovery that specific dosages of pyrimidine compositions, such as uridine compositions, can be used to treat patients diagnosed with bipolar disorder.
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Page/Page column 14
(2008/06/13)
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- Simple and efficient per-O-acetylation of carbohydrates by lithium perchlorate catalyst
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Lithium perchlorate is demonstrated to be a highly efficient and convenient catalyst for the per-O-acetylation of various saccharides with excellent yields. Graphical Abstract
- Lu, Kuo-Cheng,Hsieh, Shu-Yi,Patkar, Laxmikant N.,Chen, Chien-Tien,Lin, Chun-Cheng
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p. 8967 - 8973
(2007/10/03)
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- Catalytic nucleophilic acyl substitution of anhydrides by amphoteric vanadyl triflate
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Figure presented Among four vanadyl species examined, vanadyl triflate was the most efficient catalyst to facilitate nucleophilic acyl substitution of anhydrides with a myriad array of alcohols, amines, and thiols in high yields and high chemoselectivity. By using mixed-anhydride technique, one can achieve oleate and peptide syntheses. In marked contrast to common metal Inflates, the amphoteric character of the V=O unit in vanadyl species was proven to be responsible for the catalytic profile in this process.
- Chen, Chien-Tien,Chang, I-Hsin,Lin, Jin-Sheng,Liu, Chin-Jing,Chou, Y-Chen,Kuo, Jen-Huang,Li, Chun-Hsin,Barhate,Hon, Sang-Wen,Li, Tai-Wei,Chao, Shi-Deh,Liu, Chia-Cheng,Li, Ying-Chieh
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p. 3729 - 3732
(2007/10/03)
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- Synthesis of novel branched nucleoside dimers containing a 1,2,3- triazolyl linkage
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Three branched nucleoside dimers containing a 1,2,3-triazole linkage have been synthesized using 1,3-dipolar cycloaddition of N-3 or C-5 acetylene nucleosides with 3'-azido-3'-deoxythymidine.
- Lazrek, Hassan B.,Engels, Joachim W.,Pfleiderer, Wolfgang
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p. 1851 - 1856
(2007/10/03)
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- One-pot synthesis of nucleosides using bismuth (III) bromide as catalyst
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A peracetylated α-D-ribofuranosyl bromide reacted with silylated heterocyclic bases in the presence of bismuth (III) bromide (a non-toxic catalyst) in a one-pot procedure to give the corresponding β-D-nucleoside in good yield.
- Winum, Jean-Yves,Kamal, Mehrnaz,Barragan, Veronique,Leydet, Alain,Montero, Jean-Louis
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p. 603 - 606
(2007/10/03)
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- 4-Substituted uridine 5′-triphosphates as agonists of the P2y2 purinergic receptor
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Undine 5′-O-triphosphate (UTP) is a potent agonist of the purinergic receptor designated P2Y2. UTP is rapidly metabolized in human tissue. To find a compound with similar activity that may be more slowly metabolized, a series of 4-substituted uridine 5′-triphosphates were prepared and evaluated in a P2Y2 receptor second messenger assay. Copyright
- Shaver, Sammy R.,Pendergast, William,Siddiqi, Suhaib M.,Yerxa, Benjamin R.,Croom, Dallas K.,Dougherty, Robert W.,James, Michael K.,Neil Jones,Rideout, Janet L.
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p. 1099 - 1102
(2007/10/03)
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- Treatment of carcinoma by administration of 2'-halomethylidenyl-2'-deoxynucleosides
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This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease stat
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- 2-'-ethenylidene cytidine, uridine and guanosine derivatives
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This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease stat
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- Transformations of thiopyrimidine and thiopurine nucleosides following oxidation with dimethyldioxirane
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A general and convenient method for the synthesis of several pyrimidine and purine nucleosides by selective oxidation of thionucleosides with dimethyldioxirane is reported. Thioketo moieties in the C-4 position of the pyrimidine ring, and in the C-6, and C-8 positions of the purine ring are the domain of oxidative nucleophilic substitution. Thioketo moieties in the C-2 position of both purine and pyrimidine rings are the domain of desulfurization or formation of disulfides.
- Saladino, Raffaele,Mincione, Enrico,Crestini, Claudia,Mezzetti, Maurizio
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p. 6759 - 6780
(2007/10/03)
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- Synthesis of 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl(thymine (d4T; stavudine) from 5-methyluridine
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A practical synthetic method of d4T (3) from 5-methyluridine (2a) was developed. The Marumoto-Mansuri method was modified using 2',3'-O-methoxyethylidene-5-methyluridine (10) as an intermediate to afford 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (6a) in high yield with less formation of byproducts. The reaction mechanism was also discussed.
- Shiragami,Ineyama,Uchida,Izawa
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- Ozonation of thionucleosides. A new chemical transformation of 4-thiouracil and 6-thioguanine nucleosides to cytosine and adenosine counterparts
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The ozonation of 4-thiopyrimidine and 6-thiopurine nucleosides in presence of amines afforded selectively and under mild experimental conditions several cytidine and adenosine nucleosides. The same reaction carried out in presence of alcohols afforded O4- or O6-alkylated derivatives of the nucleosides.
- Saladino, Raffaele,Crestini, Claudia,Occhionero, Francesca,Nicoletti, Rosario
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p. 3607 - 3616
(2007/10/02)
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