- A novel synthesis and biological activity of several 5-halo-5'-amino analogues of deoxyribopyrimidine nucleosides.
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A novel synthetic procedure has been developed for the large-scale synthesis of 5-chloro-, 5-bromo-, and 5-iodo-5'-amino-2',5'-dideoxyuridine (4c-e) as well as of two new analogues, 5-iodo-5'-amino-2',5'-dideoxycytidine and 5-fluoro-5'-amino-2',5'-dideoxyuridine (4a and 4b), in good yield. The starting materials, 5-halo-2'-deoxyuridine and 5-halo-2'-deoxycytidine, are readily available and the method is straightforward. This report describes the synthesis and the biologial activities of these compounds.
- Lin,Prusoff
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- Sulfur [18F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis
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The lack of efficient [18F]fluorination processes and target-specific organofluorine chemotypes remains the major challenge of fluorine-18 positron emission tomography (PET). We report here an ultrafast isotopic exchange method for the radiosynthesis of novel PET agent aryl [18F]fluorosulfate enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully automated 18F-radiolabeling of 25 structurally and functionally diverse aryl fluorosulfates with excellent radiochemical yield (83-100%, median 98%) and high molar activity (280 GBq μmol-1) at room temperature in 30 s. The purification of radiotracers requires no time-consuming HPLC but rather a simple cartridge filtration. We further demonstrate the imaging application of a rationally designed poly(ADP-ribose) polymerase 1 (PARP1)-targeting aryl [18F]fluorosulfate by probing subcutaneous tumors in vivo.
- Zheng, Qinheng,Xu, Hongtao,Wang, Hua,Du, Wen-Ge Han,Wang, Nan,Xiong, Huan,Gu, Yuang,Noodleman, Louis,Sharpless, K. Barry,Yang, Guang,Wu, Peng
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- Stereoselective Syntheses of 3-Hydroxyamino- A nd 3-Methoxyamino-2,3-Dideoxynucleosides
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Aminonucleosides are used as key motifs in medicinal and bioconjugate chemistry; however, existing strategies toward 3-hypernucleophilic amine systems do not readily deliver deoxyribo-configured products. We report diastereoselective syntheses of deoxyribo- A nd deoxyxylo-configured 3-hydroxyamino- A nd 3-methoxyamino-nucelosides from 3-imine intermediates. The presence or absence of the 5-hydroxyl-group protection dictates facial selectivity via inter-or intramolecular delivery of hydride from BH3 (borane). Protecting group screening gave one access to previously unknown 3-methoxyamino-deoxyguanosine derivatives.
- Bose, Sritama,Hodgson, David R. W.
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- Antiviral activities of β-enantiomers of 3′-substituted-3′-deoxythymidine analogs
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Several β-L-3′-substituted-3′-deoxythymidine were stereospecifically synthesized. None of these analogs inhibited HIV-1 nor HBV replication in vitro suggesting that these β-L-pyrimidine derivatives may not be efficiently phosphorylated inside the cells Copyright
- Faraj, Abdesslem,Alaoui, M. Abdelaziz El,Pavia, Geraldine,Gosselin, Gilles,Imbach, Jean-Louis,Schinazi, Raymond F.,Sommadossi, Jean Pierre
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- Stereochemistry of internucleoside phosphorus atom affects sugar pucker and acid hydrolysis of N3′-P5′ thio-phosphoramidates
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Investigation of the sugar pucker of the two diastereomers of dinucleotide N3′-P5′-thio-phosphoramidates TNPSTNH2 and TNPSTOH shows that the Sp isomer adopts a more C3′-endo (North) sugar ring configuration than the Rp counterpart. In contrast, P-stereochemistry of oligonucleotide phosphorothioate (O3′-P5′) compounds has no effect on the nucleoside sugar puckering. This difference is also reflected in the different rate of acid hydrolysis for the two isomers. Thus, the Rp stereoisomer with less prevalent C3′-endo configuration has an acid hydrolysis rate constant ~50% higher than that of the Sp molecule. The TNPOTNH2 and TNPOTOH dinucleotides are hydrolyzed an order of magnitude faster than TNPSTNH2 and TNPSTOH, respectively. In addition, dinucleotides with the terminal 3′-OH group are hydrolyzed two times faster than their 3′-NH2 counterparts.
- Pourshahian, Soheil,Gryaznov, Sergei M.
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- 1,3-Dipolar cycloaddition of alkenes to 3'-azido-3'-deoxythymidine as a route to 3'-deoxythymidin-3'-yl derivatives
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1,3-Cycloaddition of acrylonitrile, acrylamide, vinyl acetate and allyl alcohol to azido group of 3'-azido-3'-deoxythymidine under mild conditions afforded the corresponding adducts which were tested as inhibitors of HIV reverse transcriptase.
- Solyev, Pavel N.,Novikov, Roman A.,Kukhanova, Marina K.,Jasko, Maxim V.
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- Probing the binding requirements of modified nucleosides with the dna nuclease snm1a
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SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.
- Dürr, Eva-Maria,McGouran, Joanna F.
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- Selective Inhibition of DNA Polymerase β by a Covalent Inhibitor
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DNA polymerase β (Pol β) plays a vital role in DNA repair and has been closely linked to cancer. Selective inhibitors of this enzyme are lacking. Inspired by DNA lesions produced by antitumor agents that inactivate Pol β, we have undertaken the development of covalent small-molecule inhibitors of this enzyme. Using a two-stage process involving chemically synthesized libraries, we identified a potent irreversible inhibitor (14) of Pol β (KI = 1.8 ± 0.45 μM, kinact = (7.0 ± 1.0) × 10-3 s-1). Inhibitor 14 selectively inactivates Pol β over other DNA polymerases. LC-MS/MS analysis of trypsin digests of Pol β treated with 14 identified two lysines within the polymerase binding site that are covalently modified, one of which was previously determined to play a role in DNA binding. Fluorescence anisotropy experiments show that pretreatment of Pol β with 14 prevents DNA binding. Experiments using a pro-inhibitor (pro-14) in wild type mouse embryonic fibroblasts (MEFs) indicate that the inhibitor (5 μM) is itself not cytotoxic but works synergistically with the DNA alkylating agent, methylmethanesulfonate (MMS), to kill cells. Moreover, experiments in Pol β null MEFs indicate that pro-14 is selective for the target enzyme. Finally, pro-14 also works synergistically with MMS and bleomycin to kill HeLa cells. The results suggest that pro-14 is a potentially useful tool in studies of the role of Pol β in disease.
- Yuhas, Shelby C.,Laverty, Daniel J.,Lee, Huijin,Majumdar, Ananya,Greenberg, Marc M.
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supporting information
p. 8099 - 8107
(2021/06/21)
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- Thiourea Modified Doxorubicin: A Perspective pH-Sensitive Prodrug
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A novel approach to the synthesis of pH-sensitive prodrugs has been proposed: thiourea drug modification. Resulting prodrugs can release the cytotoxic agent and the biologically active 2-thiohydantoin in the acidic environment of tumor cells. The concept of acid-catalyzed cyclization of thioureas to 2-thiohydantoins has been proven using a FRET model. Dual prodrugs of model azidothymidine, cytotoxic doxorubicin, and 2-thiohydantoin albutoin were obtained, which release the corresponding drugs in the acidic environment. The resulting doxorubicin prodrug was tested on prostate cancer cells and showed that the thiourea-modified prodrug is less cytotoxic (average IC50 ranging from 0.5584 to 0.9885 μM) than doxorubicin (IC50 ranging from 0.01258 to 0.02559 μM) in neutral pH 7.6 and has similar toxicity (average IC50 ranging from 0.4970 to 0.7994 μM) to doxorubicin (IC50 ranging from 0.2303 to 0.8110 μM) under mildly acidic conditions of cancer cells. Cellular and nuclear accumulation in PC3 tumor cells of Dox prodrug is much higher than accumulation of free doxorubicin.
- Krasnovskaya, Olga O.,Malinnikov, Vladislav M.,Dashkova, Natalia S.,Gerasimov, Vasily M.,Grishina, Irina V.,Kireev, Igor I.,Lavrushkina, Svetlana V.,Panchenko, Pavel A.,Zakharko, Marina A.,Ignatov, Pavel A.,Fedorova, Olga A.,Jonusauskas, Gediminas,Skvortsov, Dmitry A.,Kovalev, Sergey S.,Beloglazkina, Elena K.,Zyk, Nikolay V.,Majouga, Alexander G.
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p. 741 - 750
(2019/03/02)
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- 5′-silylated 3′-1,2,3-triazolyl thymidine analogues as inhibitors of West Nile Virus and Dengue virus
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West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-silyl group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ silyl group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).
- Vernekar, Sanjeev Kumar V.,Qiu, Li,Zhang, Jing,Kankanala, Jayakanth,Li, Hongmin,Geraghty, Robert J.,Wang, Zhengqiang
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p. 4016 - 4028
(2015/05/27)
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- Synthesis and Self-Assembly of Bolaamphiphiles Based on β-Amino Acids or an Alcohol
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The synthesis of bolaamphiphiles from unusual β-amino acids or an alcohol and C12 or C20 spacers is described. Unusual β-amino acids such as a sugar amino acid, an AZT-derived amino acid, a norbornene amino acid, and an AZT-derived amino alcohol were coupled with spacers under standard conditions to get the novel bolaamphiphiles 5-8 (Scheme 1), 12 and 13 (Scheme 2), and 17 and 20 (Scheme 3). Some of these compounds, on precipitation from MeOH/H2O, self-assembled into organized molecular structures. Copyright
- Mainkar, Prathama S.,Sridhar, Chirumarry,Sudhakar, Ambadi,Chandrasekhar, Srivari
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- Antimycobacterial activities of 5-alkyl (or halo)-3′-substituted pyrimidine nucleoside analogs
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Several 5-alkyl (or halo)-3′-azido (amino or halo) analogs of pyrimidine nucleosides have been synthesized and evaluated against Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium. Among these compounds, 3′-azido-5-ethyl-2′,3′-dideoxyuridine (3) was found to have significant antimycobacterial activities against M. bovis (MIC 50 = 1 μg/mL), M. tuberculosis (MIC50 = 10 μg/mL) and M. avium (MIC50 = 10 μg/mL).
- Srivastav, Naveen C.,Shakya, Neeraj,Bhavanam, Sudha,Agrawal, Amogh,Tse, Chris,Desroches, Nancy,Kunimoto, Dennis Y.,Kumar, Rakesh
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supporting information; experimental part
p. 1091 - 1094
(2012/03/26)
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- Investigation of reactions postulated to occur during inhibition of ribonucleotide reductases by 2′-azido-2′-deoxynucleotides
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Model 3′-azido-3′-deoxynucleosides with thiol or vicinal dithiol substituents at C2′ or C5′ were synthesized to study reactions postulated to occur during inhibition of ribonucleotide reductases by 2′-azido-2′-deoxynucleotides. Esterification of 5′-(tert-
- Dang, Thao P.,Sobczak, Adam J.,Mebel, Alexander M.,Chatgilialoglu, Chryssostomos,Wnuk, Stanislaw F.
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experimental part
p. 5655 - 5667
(2012/09/25)
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- Synthesis and biological activities of novel s-triazine bridged dinucleoside analogs
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A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H2O. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated. Copyright
- Shen, Fengjuan,Li, Xiaoliu,Zhang, Xiaojuan,Qin, Zhanbin,Yin, Qingmei,Chen, Hua,Zhang, Jinchao
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scheme or table
p. 1205 - 1210
(2012/03/26)
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- Compensatory effects of the human nucleoside transporters on the response to nucleoside-derived drugs in breast cancer MCF7 cells
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Nucleoside transporters (NTs) are involved in the cytotoxicity and transcriptomic response induced by nucleoside analogues. A relationship between the expression of nucleoside transporters and response to therapy has been demonstrated in solid tumours, although the pattern of such expression is highly variable. Thus, a question is whether the transporter expression pattern rather than specific NT proteins might better explain the ability of tumour cells to respond to nucleoside-derived drug therapy. In this study we used the breast cancer cell lines MCF7 and MCF7-hCNT1 (stably transfected with hCNT1) to determine whether hCNT1 expression can complement hENT1 functional loss in the cytotoxicity and transcriptomic response triggered by nucleoside analogues. Expression of hCNT1 slightly increased cell sensitivity to 5′-deoxy-5-fluorouridine (5′-DFUR). Inhibition of the endogenous equilibrative activity blocked 5′-DFUR cytotoxicity in MCF7 cells, but not in MCF7-hCNT1 cells. Moreover, under equilibrative transport inhibition conditions, induction of some transcriptional targets of 5′-DFUR was blocked in MCF7 cells, whereas ENT-inhibition had no effect on the transcriptional response to 5′-DFUR in MCF7-hCNT1 cells. To confirm the role of hCNT1 in 5′-DFUR treatment, a panel of nucleoside derivatives suitable for hCNT1-inhibition was obtained. The molecule T-Ala inhibited hCNT1-mediated transport. Furthermore, the cytotoxic action of 5′-DFUR and the transcriptional changes produced by this nucleoside analogue were partially inhibited by T-Ala in MCF7-hCNT1 cells. These results show a link between NT function and the pharmacogenomic response to nucleoside analogues and further support the hypothesis that the expression pattern rather than specific transporters determines the cytotoxic effect of nucleoside derivatives.
- Cano-Soldado, Pedro,Molina-Arcas, Miriam,Alguero, Berta,Larrayoz, Ignacio,Lostao, M. Pilar,Grandas, Anna,Casado, F.Javier,Pastor-Anglada, Marcal
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p. 639 - 648
(2008/03/14)
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- Foldamers derived from nucleoside β-amino acids: PNA or DNA? Can we have both in one place?
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The synthesis of a modified thymidine (nucleoside β-amino acid) monomer and preliminary investigations into the solid phase peptide synthesis of PNA/DNA chimeras containing a neutral, internucleoside amide linkage are described. Copyright Taylor & Francis Group, LLC.
- Threlfall, Richard,Davies, Andrew,Howarth, Nicola,Cosstick, Richard
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p. 611 - 614
(2008/09/17)
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- Radical reactions in aqueous medium using (Me3Si)3SiH
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(Chemical Equation Presented) (Me3Si)3SiH was used as a successful reagent in a variety of radical-based transformations in water. The system comprising substrate, silane, and initiator (ACCN) mixed in aqueous medium at 100°C worked well for both hydrophilic and hydrophobic substrates, with the only variation that an amphiphilic thiol was also needed in case of the water-soluble compounds.
- Postigo, Al,Kopsov, Sergey,Ferreri, Carla,Chatgilialoglu, Chryssostomos
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p. 5159 - 5162
(2008/09/17)
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- POLYMERASE-INDEPENDENT ANALYSIS OF THE SEQUENCE OF POLYNUCLEOTIDES
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The present invention concerns methods of polymerase independent template directed elongation of polynucleotides, nucleotide building blocks used in these methods as well as the use of the methods and building blocks for the determination of nucleotide sequences, in particular for the determination of SNPs, base modifications, mutations, rearrangements and methylation patterns.
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Page/Page column 53-54
(2008/06/13)
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- Linker-free fluorophore-labeled oligonucleotides: Synthesis of 3′-fluoresceinylthymidine building blocks and their coupling reactions
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Reported here are the syntheses of two thymidine derivatives with an amide-linked 6-carboxyfluorescein residue at their 3′-position that are suitable for the synthesis of fluorophore-labeled oligonucleotides. The first is a 5′-phosphoramidite with a pivaloyl-protected carboxyfluorescein residue in the lactone form. It was prepared from 3′-azido-3′- deoxythymidine (AZT) in three steps and 73% overall yield and coupled on solid support. The second is an imidazolide of thymidine 5′-monophosphate that was obtained from AZT in five steps and 48% overall yield. The imidazolide can be coupled to amino-terminated nucleic acids in aqueous solution. Georg Thieme Verlag Stuttgart.
- Griesang, Niels,Kervio, Eric,Richert, Clemens
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p. 2327 - 2334
(2007/10/03)
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- An efficient synthesis of 3′-amino-3′-deoxythymidine derivatives
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An efficient method of reduction of 3′-azido-3′-deoxythymidine and its 5′-protected derivatives to 3′-aminothymidine derivatives on a palladium catalyst using ammonium formate as a source of hydrogen was suggested.
- Seregin,Chudinov,Yurkevich,Shvets
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p. 135 - 138
(2007/10/03)
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- Hydrolytic reactions of 3′-N-phosphoramidate and 3′-N-thiophosphoramidate analogs of thymidylyl-3′,5′-thymidine
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The diastereomeric thiophosphoramidate analogs [(RP)- and (SP)-3′,5′-Tnp(s)T] 2 and the phosphoramidate analog [3′,5′-TnpT] 3 of thymidylyl-3′,5′-thymidine were prepared and their hydrolytic reactions over the pH-range 1-8 at 363.2 K
- Ora, Mikko,Murtola, Merita,Aho, Sami,Oivanen, Mikko
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p. 593 - 600
(2007/10/03)
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- A general Staudinger protocol for solution-phase parallel synthesis
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The Staudinger reaction has been adapted for parallel synthesis by the application of fluorous-tethered triphenyl phosphine. The fluorous-tethered triphenylphosphine is expediently removed in parallel by FluoroFlash SPE columns to afford functionalized amines in high yields and purities.
- Lindsley, Craig W,Zhao, Zhijian,Newton, Randall C,Leister, William H,Strauss, Kimberly A
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p. 4467 - 4470
(2007/10/03)
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- A facile method for deprotection of trityl ethers using column chromatography
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A mild, efficient and inexpensive detritylation method is reported that uses trifluoroacetic acid on a silica gel column to obtain pure, detritylated compounds in one-step. This method is applicable to acid stable as well as acid sensitive compounds with only slight alterations in the procedure. Nineteen examples are given.
- Pathak, Ashish K.,Pathak, Vibha,Seitz, Lainne E.,Tiwari, Kamal N.,Akhtar, Mohammad S.,Reynolds, Robert C
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p. 7755 - 7757
(2007/10/03)
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- The synthesis of 3'- and 5'-iminodiacetic acid derivatives of thymidine and their incorporation into synthetic oligonucleotides
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The syntheses of thymidines modified with iminodiacetic acid (IDA) at the 3' (1) or 5' (2) positions have been accomplished. These modified nucleotides have been incorporated into synthetic oligonucleotides. (C) 2000 Elsevier Science Ltd.
- Jonklaas, M. Devan,Kane, Robert R.
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p. 4035 - 4037
(2007/10/03)
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- Conformationally locked nucleosides. Synthesis of oligodeoxynucleotides containing 3'-amino-3'-deoxy-3'-N,5'(R)-C-ethylenethymidine
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3'-Amino-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-N,5'(R)-C-ethylenethymidine (6) was synthesized starting from 3'-azido-3'-deoxythymidine. Condensation of 6 with 5'-O-(H-phosphonyl)thymidine and 5'-O-(p-nitrophenoxycarbonyl)thymidine derivatives gave dinucleotide and dinucleoside derivatives, respectively, which were incorporated into oligodeoxynucleotides (ODNs). Tm data of the modified ODNs are also presented.
- Wang,Stoisavljevic
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p. 1413 - 1425
(2007/10/03)
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- Conformationally locked nucleosides. Synthesis and stereochemical assignments of 3'-N,5'-C-bridged 3'-amino-3'-deoxythymidines
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3'-Amino-3'-deoxythymidine was converted, in multi-steps, to its 5'-O- (4,4'-dimethoxytrityl)-5'-C-tosyloxyethyl-3'-N-carbobenzoxy derivative 7 and 5'-C-mesyloxyethyl-3'-N-(9-fluorenyl)methoxycarbonyl derivatives 6 and 11. Subsequent hydrogenolysis or treatment with DMAP afforded 3'-N,5'-C-bridged bicyclic thymidines. Stereochemical assignments were accomplished with the help of NOE.
- Wang, Guangyi
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p. 6343 - 6346
(2007/10/03)
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- Asymmetric synthesis of nucleosides via molybdenum-catalyzed alkynol cycloisomerization coupled with stereoselective glycosylations of deoxyfuranose glycals and 3-amidofuranose glycals
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Deoxygenated furanose glycals were efficiently prepared by molybdenum pentacarbonyl-catalyzed cycloisomerization of alkynyl alcohols, which were easily prepared in chiral nonracemic form by short synthetic sequences featuring asymmetric epoxidations of commercially available allylic alcohols. The cycloisomerization reaction was demonstrated to be compatible with ester and amide functional groups. A 2,3-dideoxyfuranose glycal was stereoselectively converted into the anti-AIDS β-nucleoside stavudine (2',3'-didehydro-2',3'-dideoxythymidine, d4T) and the antiviral 3'-deoxy-β-nucleoside cordycepin. The anchimeric and hydrogen-bond-directing effects of 3-amido-2,3-dideoxyfuranose glycals were exploited in a novel and highly stereoselective synthesis strategy for a variety of biologically active 3'-amino-2',3'-dideoxy- and 3'-amino-3'-deoxy-β-nucleosides, including puromycin aminonucleoside. In addition, the mechanism of the molybdenum-catalyzed alkynol cycloisomerization reaction has been studied. Evidence is presented which indicates that cyclic molybdenum carbene anions are catalytic intermediates in these cyclizations.
- McDonald, Frank E.,Gleason, Mark M.
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p. 6648 - 6659
(2007/10/03)
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- Synthesis and antiviral evaluation of 3'-substituted thymidine analogues derived from 3'-amino-3'-deoxythymidine
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To assess the structure-activity relationship for antiviral activity, a series of 3'-deoxy-3'-N-functionalized thymidine analogues were synthesized. Several of these thymidine analogues show moderate in vitro activity against HIV-1 and HIV-2.
- Pannecouque,Van Poppel,Balzarini,Claes,De Clercq,Herdewijn
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p. 541 - 544
(2007/10/02)
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- Chemical-enzymatic synthesis of 3'-amino-2',3'-dideoxy-β-D- ribofuranosides of natural heterocyclic bases and their 5'-monophosphates
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Treatment of O2,3'-anhydro-5'-O-trityl derivatives of thymidine (1) and 2'-deoxyuridine (2) with lithium azide in dimethylformamide at 150 °C resulted in the formation of the corresponding isomeric 3'-azido-2',3'- dideoxy-5'-O-trityl-β-D-ribofuranosyl N1- (the major products) and N3- nucleosides 3/4 and 5/6). 3'-Amino-2',3'-dideoxy-β-D-ribofuranosides of thymidine [Thd(3'NH2)], uridine [dUrd(3'NH2)], and cytidine [dCyd(3'NH2)] were synthesized from the corresponding 3'-azido derivatives. The Thd(3'NH2) and dUrd(3'NH2) were used as donors of carbohydrate moiety in the reaction of enzymatic transglycosylation of adenine and guanine to afford dAdo(3'NH2) and dGuo(3'NH2). The substrate activity of dN(3'NH2) vs. nucleoside phosphotransferase of the whole cells of Erwinia herbicola was studied.
- Zaitseva,Kvasyuk,Vaaks,Barai,Bokut,Zinchenko,Mikhailopulo
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p. 819 - 834
(2007/10/02)
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- Synthesis and evaluation of new 2',3'-dideoxynucleoside analogs as potential anti-AIDS and anti-herpes drugs
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Based on the known structure-activity relationships for the active anti-HIV, a series of 3'-deoxy-3'-N-functionalized thymidine analogs has been synthesized from thymidine. Evaluation for inhibitory activity against human immunodeficiency virus (HIV) replication in CEM cells and against herpes simplex virus in MRC-5 cells is reported.
- Faraj,Maillard,Lemaitre,Letellier,Frappier,Florent,Grierson,Monneret,Zerial
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p. 141 - 148
(2007/10/02)
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- SELECTIVE HYDROGENATION OF ORGANIC AZIDES TO AMINES BY INTERLAMELLAR MONTMORILLONITEDIPHENYLPHOSPHINE PALLADIUM(II) CATALYST
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Organic azides are selectively and catalytically hydrogenated to amines by a heterogenized homogeneous catalyst for the first time.
- Sharma, G. V. M.,Chandrasekhar, S.
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p. 3289 - 3294
(2007/10/02)
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- SYNTHESIS OF 3'SUBSTITUTED-2',3'-DIDEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTI-AIDS DRUGS
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3'-Amino-3'-deoxythymidine 9 was prepared in six steps and in 67percent overall yield from thymidine.Five derivatives of 9 and compound 17 were tested for their anti-HIV activity.
- Maillard, Michel,Faraj, Abdesslem,Frappier, Francois,Florent, Jean-Claude,Grierson, David S.,Monneret, Claude
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p. 1955 - 1958
(2007/10/02)
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- Nucleosides. 115. Reaction of 3'-O-Mesylthymidine. Formation of 1-(3-Azido-2,3-dideoxy-β-D-threo-pentofuranosyl)thymine and Its Conversion into 6,3'-Imino-1-(2,3-dideoxy-β-D-threo-pentofuranosyl)thymine
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Treatment of 5'-O-trityl-3'-O-mesylthymidine (3) with NaN3 in DMF at reflux gave 5'-O-trityl-3'-azido-3'-deoxythymidine (5) and 6,3'-imino-1-(5-O-trityl-3-deoxy-β-D-threo-pentofuranosyl)thymine (8).Compound 8 was formed from the 3'-azido-threo-pentofuranosylthymine derivative 6.A mechanism is proposed for the formation of 8 from 6.Also, the 6,5'-imino-bridged thymidine 18 was prepared.Conformational features of these imino-bridged nucleosides are discussed.
- Matsuda, Akira,Watanabe, Kyoichi A.,Fox, Jack J.
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p. 3274 - 3278
(2007/10/02)
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- Nitrosourea analogs of thymidine
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Alkyl and haloalkyl nitrosourea analogs of thymidine are useful in the treatment of cancers in mice.
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