- Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides
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Inhibition of DNA repair enzymes tyrosyl-DNA phosphodiesterase 1 and poly(ADP-ribose) polymerases 1 and 2 in the presence of pyrimidine nucleoside derivatives was studied here. New effective Tdp1 inhibitors were found in a series of nucleoside derivatives possessing 2′,3′,5′-tri-O-benzoyl-d-ribofuranose and 5-substituted uracil moieties and have half-maximal inhibitory concentrations (IC50) in the lower micromolar and submicromolar range. 2′,3′,5′-Tri-Obenzoyl- 5-iodouridinemanifested the strongest inhibitory effect on Tdp1 (IC50 = 0.6 μM). Adecrease in the number of benzoic acid residues led to a marked decline in the inhibitory activity, and pyrimidine nucleosides lacking lipophilic groups (uridine, 5-fluorouridine, 5-chlorouridine, 5-bromouridine, 5-iodouridine, and ribothymidine) did not cause noticeable inhibition of Tdp1 (IC50 > 50 μM). No PARP1/2 inhibitors were found among the studied compounds (residual activity in the presence of 1mMsubstances was 50-100%). Several O-benzoylated uridine and cytidine derivatives strengthened the action of topotecan on HeLa cervical cancer cells.
- Chernyshova, Irina A.,Drenichev, Mikhail S.,Dyrkheeva, Nadezhda S.,Ilina, Ekaterina S.,Ivanov, Georgy A.,Lavrik, Olga I.,Mikhailov, Sergey N.,Oslovsky, Vladimir E.,Zakharenko, Alexandra L.
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Read Online
- An efficient method for the synthesis of β-D-ribonucleosides catalyzed by metal iodides
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Several β-D-ribonucleosides were synthesized in high yields under mild conditions by N-glycosylations of methyl 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl carbonate (1) with trimethylsilylated nucleoside bases in acetonitrile using a catalytic amount of metal iodide such as SnI2, SbI3 or TeI4. A deprotection of N6-benzoyl group of coupling product took place to a considerable extent when N6-benzoyl-N6,N9-bis(trimethylsilyl)adenine was employed as a nucleoside base using SnI2 or SnCI2 as a catalyst while it was minimized when SbI3 or TeI4 was used. Further, the N-glycosylation of 1 with 7-trimethylsilyltheophylline in the presence of a catalytic amount of metal iodide was more effectively achieved in nitrile solvents other than acetonitrile.
- Mukaiyama, Teruaki,Nagai, Masashi,Matsutani, Takafumi,Shimomura, Naoyuki
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Read Online
- Tin(II) Chloride Catalyzed Synthesis of β-D-Ribonucleosides
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Several β-D-ribonucleosides are stereoselectively synthesized in high yields from methyl 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl carbonate and trimethylsilylated nucleoside bases such as pertrimethylsilylated uracil and adenine under mild conditions by using a catalytic amount of tin(II) chloride, a weak Lewis acid.
- Mukaiyama, Teruaki,Matsutani, Takafumi,Shimomura, Naoyuki
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Read Online
- MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF
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The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.
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Page/Page column 115-116
(2021/02/19)
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- NIS/TMSOTf-Promoted Glycosidation of Glycosyl ortho-Hexynylbenzoates for Versatile Synthesis of O-Glycosides and Nucleosides
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Glycosidation plays a pivotal role in the synthesis of O-glycosides and nucleosides that mediate a diverse range of biological processes. However, efficient glycosidation approach for the synthesis of both O-glycosides and nucleosides remains challenging in terms of glycosidation yields, mild reaction conditions, readily available glycosyl donors, and cheap promoters. Here, we report a versatile N-iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf)-promoted glycosidation approach with glycosyl ortho-hexynylbenzoates as donors for the highly efficient synthesis of O-glycosides and nucleosides. The glycosidation approach highlights the merits of mild reaction conditions, cheap promoters, extremely wide substrate scope, and good to excellent yields. Notably, the glycosidation approach performs very well in the construction of a series of challenging O- and N-glycosidic linkages. The glycosidation approach is then applied to the efficient synthesis of oligosaccharides via the one-pot strategy and the stepwise strategy. On the basis of the isolation and characterization of the departure species derived from the leaving group, a plausible mechanism of NIS/TMSOTf-promoted glycosidation of glycosyl ortho-hexynylbenzoates is proposed.
- Liu, Rongkun,Hua, Qingting,Lou, Qixin,Wang, Jiazhe,Li, Xiaona,Ma, Zhi,Yang, You
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p. 4763 - 4778
(2021/04/06)
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- Ortho-(1-phenylvinyl)benzoate glycosylation donor, and preparation method and application thereof
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The invention discloses an ortho-(1-phenylvinyl)benzoate glycosylation donor, and a preparation method and an application thereof in a glycosylation reaction. The ortho-(1-phenylvinyl)benzoate glycosylation donor is stable, is easy to prepare and store, and is widely applied to the construction of various oxygen glucosides and nucleoside (nitrogen glucoside) glycosidic bonds. The leaving group ofthe donor is an alkenyl ester, has a high activity, and can be combined with thioglycoside or n-pentenyl ether glucoside through a one-pot glycosylation reaction to synthesize oligosaccharide. The glycosylation reaction conditions are mild, and receptors sensitive to acid and electrophilic reagents can tolerate the glycosylation reaction conditions.
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Paragraph 0193; 0197-0199
(2020/05/01)
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- 3-methyl uridine and 4-methyl cytidine nucleoside compound, synthetic method and its pharmaceutical use
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The invention discloses a 3-methyluridine and 4-methylcytidine nucleosides compound and a synthesis method and pharmaceutical application thereof, belonging to the field of medicinal chemistry. The compound has a structural formula as shown in the specification. The compound has the effects of simultaneously modifying sugar rings and basic groups, increasing the activity of the compound and reducing the toxicity, provides a good application prospect for development of like medicines and can be applied to preparation of anti-HBV (Hepatitis B virus) medicines. The synthesis method is simple and feasible and provides conditions for mass synthesis of the compound.
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Paragraph 0021; 0032
(2016/10/08)
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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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- Propargyl 1,2-orthoesters for a catalytic and stereoselective synthesis of pyrimidine nucleosides
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Pyrimidine nucleosides are synthesized by using propargyl 1,2-orthoesters and Au(III) salt as a catalyst. Strategically positioned 1,2-orthoesters are found to yield only 1,2-trans nucleosides and enable preparation of 2′-OH containing pyrimidine nucleosides. The glycosyl donor employed in this study is stable and easily accessible. The identified high-yielding protocol is mild, diastereoselective, and catalytic.
- Rao, Boddu Venkateswara,Manmode, Sujit,Hotha, Srinivas
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p. 1499 - 1505
(2015/02/19)
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- A Reverse Strategy for synthesis of nucleosides based on n-pentenyl orthoester donors
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Strategically derivatized NPOE glycosyl donors, are able to efficiently glycosylate silylated nucleobases under mild conditions, even as low as -78°C if necessary. Ensuring trans-1,2 glycosylation, thus permitting, unlike classical procedures, a Reverse Strategy for the synthesis of ribonucleosides, where glycosylation occurs late, rather than early, and convergency is optimized.
- Fraser-Reid, Bert,Ganney, Parimala,Ramamurty, Changalvala V. S.,Gomez, Ana M.,Lopez, J. Cristobal
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supporting information
p. 3251 - 3253
(2013/05/08)
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- Synthesis and cytotoxic activity of novel 5-substituted-1-(β-L- arabinofuranosyl) pyrimidine nucleosides
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A series of new 5-halogeno-1-(β-L-arabinofuranosyl)uracils and their cytosine analogues were synthesized by halogenation of ara-L-uridine and ara-L-cytidine, respectively. The 5-(2-thienyl) and 5-halogenothienyl derivatives of both series were also prepared in excellent yields by Stille coupling followed by halogenation. All of these syntheses were based on benzoyl-protected derivatives. In vitro cytotoxicity experiments carried out using L1210 mouse leukemia cells showed that 5-(2-thienyl)- ara-L-uridine was the most potent compound of the new compounds; the majority of the analogues were not effective up to 200 μM concentrations. Copyright Taylor and Francis Group, LLC.
- Sendula, Robert,Orban, Erika,Hudecz, Ferenc,Sagi, Gyula,Jablonkai, Istvan
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experimental part
p. 482 - 500
(2012/07/28)
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- An economical synthesis of D- and L-pyrimidine arabinoand ribonucleosides
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The one-step synthesis of several β-D/L-arabino- and ribonucleosides was performed in good yields under reflux or microwave-assisted fusion method. A comparison of the two methods showed that better yields were obtained using the reflux conditions. Copyright Taylor and Francis Group, LLC.
- Lazrek, Hassan B.,Ouzebla, Driss,Faraj, Abdesslem
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experimental part
p. 227 - 234
(2012/04/18)
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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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- One-flow, multistep synthesis of nucleosides by Bronsted acid-catalyzed glycosylation
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Nucleosides in flow: A general, scalable method of Bronsted acid-catalyzed nucleoside formation is described. Because of the high reaction temperatures readily available to the flow reaction format, mild Bronsted acids, particularly pyridinium triflates, can be used. A one-flow multistep synthesis of unprotected nucleosides is also reported (see scheme).
- Sniady, Adam,Bedore, Matthew W.,Jamison, Timothy F.
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supporting information; experimental part
p. 2155 - 2158
(2011/04/23)
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- An improved procedure for nucleoside synthesis using glycosyl trifluoroacetimidates as donors
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Using glycosyl trifluoroacetimidates as donors and nitromethane (or acetonitrile) as solvent, silylation and subsequent glycosylation were realized in a 'one-pot' procedure to provide the corresponding nucleosides derivatives in high yields.{A figure is p
- Liao, Jinxi,Sun, Jiansong,Yu, Biao
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experimental part
p. 1034 - 1038
(2009/09/05)
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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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- Trifluoromethylation of alkenyl bromides and iodides (including 5-iodouracils) with (CF3)2Hg and Cu (" trifluoromethylcopper")
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Bromo- and iodoalkenes undergo trifluoromethylation efficiently in DMA with "CF3Cu" generated from (CF3)2Hg and Cu. Variable stereochemical inversion is observed with substrates having a gem-carbonyl group. Substrates having gem-hydrogen, -alkyl, or -alkenyl groups give products with stereochemical retention.
- Nowak, Ireneusz,Robins, Morris J.
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p. 2678 - 2681
(2007/10/03)
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- High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
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The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
- Bookser, Brett C.,Raffaele, Nicholas B.
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p. 173 - 179
(2007/10/03)
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- Improved synthesis of oligonucleotides containing 2-thiouridine derivatives by use of diluted iodine solution
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It is known that the 2-thiocarbonyl group of 2-thiouridine (s2U) derivatives reacts easily with various oxidizing agents used in oligonucleotide synthesis to give a complex mixture. In this letter, we report an improved method for the synthesis of oligonucleotides containing s2U derivatives. It turned out that the 2-thiocarbonyl group of oligonucleotides containing s2U derivatives was stable in a 0.02 M solution of iodine in pyridine-THF-H2O. These conditions were successfully applied to the synthesis of oligonucleotides containing s2U derivatives on an automated DNA/RNA synthesizer. Moreover, no undesirable side reactions were detected so that these modified oligonucleotides could be obtained in markedly improved yields.
- Okamoto, Itaru,Seio, Kohji,Sekine, Mitsuo
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p. 583 - 585
(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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- The synthesis of [(β-D-ribofuranosyloxy)-methyl]nucleosides
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The coupling reaction of acetoxymethoxy ribofuranoside 4 with nucleic acid bases 5a-f to synthesize novel (ribofuranosyloxy)methyl uracil, thymine, cytosine, adenine, guanine derivatives 6a-g respectively in preference to the expected formation of natural nucleosides 2′,3′,5′ -tri-O-benzoyl uridine, methyluridine, cytidine, adenosine and guanosine 7a-g is described. Detailed study of these reactions catalysed by Lewis acids TMSOTf and SnCl4 is described. TMSOTf exhibited selectivity for the formation of ribofuranosyloxy methyl derivatives 6a-g rather than 7a-g. Reason for formation of 6a-g is explained by HSAB principle.
- Mereyala, Hari Babu,Mamidyala, Sreeman Kumar
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p. 655 - 669
(2007/10/03)
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- Anti-HCV nucleoside derivatives
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The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
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- Solid-phase synthesis (SPS) of substituted uracils via Oxone cleavage methodology
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An original and highly efficient Oxone cleavage methodology for the solid-phase synthesis of substituted uracils has been developed. An example of application of this methodology to the solid-phase synthesis of uridine derivatives is also reported.
- Petricci, Elena,Renzulli, Michela,Radi, Marco,Corelli, Federico,Botta, Maurizio
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p. 9667 - 9670
(2007/10/03)
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- Enantioselective synthesis and biological evaluation of 5-o-carboranyl pyrimidine nucleosides
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Base-modified carborane-containing nucleosides such as 5-o-carboranyl-2'-deoxyuridine (CDU) when combined with neutrons have potential for the treatment of certain malignancies. Lack of toxicity in various cells, high accumulation in cancer cells and intracellular phosphorylation are desirable characteristics for modified nucleosides used in boron neutron capture therapy (BNCT) for brain tumors and other malignancies. The aim of this work was to synthesize the two β-enantiomers of several 5-o-carboranyl-containing nucleosides. These derivatives may possess favorable properties such as high lipophilicity, high transportability, the ability to be phosphorylated, and resistance to catabolism. β-Isomers of 2',3'-dihydroxynucleosides and analogues containing a heteroatom in the sugar moiety were also synthesized. Carboranyl pyrimidine nucleosides were prepared either from the parent β-D-nucleoside, β-L-nucleoside, or by a coupling reaction. The dioxolane derivative 7Scheme 1Reagents and conditions: (a) 1,1,1,3,3,3-hexamethydisilazane, ammonium sulfate, reflux, 6 h; (b) tin(IV) chloride, CH2Cl2, 0°C, 2h; (c) tetrabutylammonium fluoride, 1 M sol in THF, 0°C, 3h. was prepared by a coupling reaction between protected 5-o-carboranyluracil (8, CU) and the corresponding protected heterocycle. Specific catalysts were used during the N-glycosylation process to favor the formation of the β-isomer. Biological evaluation of these new chiral 5-o-carboranyl pyrimidine derivatives indicated that most of these compounds have low toxicity in a variety of normal and malignant cells and achieved high cellular levels in a lymphoblastoid cell line. Increasing the number of hydroxyl groups on the sugar moiety decreased the cellular accumulation and serum binding to different extents. Five compounds were identified for further biological evaluation as potential agents for BNCT. Copyright (C) 1999 Elsevier Science Ltd.
- Mourier, Nicolas S.,Eleuteri, Alessandra,Hurwitz, Selwyn J.,Tharnish, Phillip M.,Schinazi, Raymond F.
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p. 2759 - 2766
(2007/10/03)
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- L-Ribonucleosides from L-xylose
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L-Xylose was converted into a L-ribose derivative via an oxidation/reduction procedure. The L-ribosyl donor was submitted to a glycosidation reaction according to Vorbruggen's conditions to give L- ribonucleosides (L-uridine, L-cytidine, L-adenosine and L-guanosine) in high yield.
- Moyroud, Elisabeth,Strazewski, Peter
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p. 1277 - 1284
(2007/10/03)
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- L-ribonucileosides for racemic RNA
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Two L-ribosyl donors were synthesised from L-xylose, then submitted to a glycosidation reaction according to Vorbruggen's conditions to furnish L- ribonucleosides in high yield.
- Moyroud,Botta,Strazewski
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p. 693 - 695
(2007/10/03)
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- Improvements in the synthesis of L-ribonucleosides for the preparation of mirror-image oligoribonucleotides
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Different improvements are described for the chemical synthesis of L- ribonucleosides corresponding to the four natural bases. These nucleosides properly protected were used to synthesize successfully a 27-base long L- oligoribonucleotide.
- Santamaria,Rayner
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p. 1405 - 1406
(2007/10/03)
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- Chirally-modified oligonucleotides and the control of gene expression. The case of L-DNAs and -RNAs
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The affinity of L-DNAs, L-RNAs and LD-DNAs for homopurine · homopyrimidine d.s. D-DNA and s.s. D-RNA was probed by gel electrophoresis and CD spectroscopy. It was found that the L-modified oligomers do not bind to d.s. DNA and to natural RNA that contains all four natural bases. Thus they cannot be used, in general, for the control of gene expression according to the antigene and antisense methodologies. Heterochiral complexes with 1:1 stoichiometry and low hem stability are formed, instead, by homopurinic L- RNA or L/D-DNA and homopyrimidinic L-RNA with the W/C complementary natural RNA sequences.
- Garbesi, Anna,Capobianco, Massimo L.,Colonna, Francesco P.,Maffini, Mauro,Niccolai, Daniela,Tondelli, Luisa
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p. 1275 - 1287
(2007/10/03)
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- L-ribofuranosyl nucleosides
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This invention relates to α and β L-ribofuranosyl nucleosides, processes for their preparation, pharmaceutical compositions containing them, and methods of using them to treat various diseases in mammals.
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- Stereoselective syntheses of β-D-ribonucleosides catalyzed by the combined use of silver salts and diphenyltin sulfide or Lawesson's reagent
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β-D-Ribonucleosides are stereoselectively synthesized in high yields from methyl 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl carbonate and trimethylsilylated nucleoside bases by the use of [diphenyltin sulfide/silver salt] or [Lawesson's reagent/silver salt] combined catalyst system under mild conditions.
- Shimomura,Matsutani,Mukaiyama
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p. 3100 - 3106
(2007/10/02)
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- A New Direct Glycosylation of Pyrimidine, Pyrazole, Imidazole and Purine Heterocycles via their N-tetrahydropyranyl (THP) Derivatives
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Pyrimidine, pyrazole, imidazole and purine N-tetrahydropyranyl (THP) derivatives have been converted in one-pot and in a regio- and stereo-selective manner into the corresponding β-D-2',3',5'-tri-O-benzoyl ribofuranosyl nucleoside derivatives on treatment with 1-β-acetyl-2',3',5'-tri-O-benzoyl-ribofuranose, hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCl), and trimethylsilyl triflate (TMST).
- Manfredini, Stefano,Baraldi, Pier Giovanni,Bazzanini, Rita,Guarneri, Mario,Simoni, Daniele
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p. 583 - 584
(2007/10/02)
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- Catalytic Stereoselective Synthesis of β-Ribonucleosides from Methyl Ribofuranosyl Carbonate and Trimethylsilylated Nucleoside Bases by Combined Use of Silver Salts and Diphenyltin Sulfide
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Catalytic stereoselective synthesis of several ribonucleosides from 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl methyl carbonate and trimethylsilylated nucleoside bases is efficiently carried out by combined use of silver salts and diphenyltin sulfide (Ph2Sn=S) under mild conditions.
- Mukaiyama, Teruaki,Matsutani, Takafumi,Shimomura, Naoyuki
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p. 1627 - 1630
(2007/10/02)
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- Phenylsulfenyl D-Ribofuranosides as Efficient Ribosyl Donors: Application to the Synthesis of -(Deoxy)Nucleosides
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Readily available phenylsulfenyl 2,3,5-tri-O-benzoyl-β-D-ribofuranoside glycosylates silylated nucleobases in a fast, high-yielding and stereoselective reaction promoted by trimethylsilyl trifluoromethanesulfonate.The method has been applied to the synthesis of labelled nucleosides further transformed to building blocks ready for oligodeoxynucleotide construction. Key words: anomeric sulfoxides; silylated nucleobases; nucleosides; 2'-deoxynucleosides.
- Chanteloup, Luc,Beau, Jean-Marie
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p. 5347 - 5350
(2007/10/02)
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- Condensation of 1-Fluorofuranones and Silylated Nucleobases Catalyzed by Tetrafluorosilane
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The title reaction provides a generally useful tool for nucleoside synthesis.The stereoselectivities are highly influenced by the fluoride substrates, and steric course of the reaction of O-benzylated ribofuranosyl fluoride is solvent dependent.
- Noyori, Ryoji,Hayashi, Masahiko
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- 5'-O-ALKYL-5-FLUOROURIDINES: SYNTHESIS AND BIOLOGICAL ACTIVITY
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Methyl 2,3-O-isopropylidene-D-ribofuranoside (IV) was alkylated with alkyl halides in the presence of sodium hydride and the products were transformed by acid hydrolysis and glycosylation into methyl 5-O-alkyl-D-ribofuranosides VII.Benzoylation of VII followed by acetolysis afforded 1-O-acetyl-2,3-di-O-benzoyl-5-O-alkyl-D-ribofuranoses IX which on reaction with 2,4-bis(trimethylsilyloxy)pyrimidine in the presence of tin tetrachloride in acetonitrile and subsequent hydrolysis gave 5'-O-alkyl-2',3'-di-O-benzoyluridines XIa-XIe.Methanolysis of compounds XI furnished 5'-O-alkyluridines III.The 5-O-allyl derivative XII was hydroxylated in the presence of OsO4 and transformed further to 5'-O-(RS)-(2,3-dihydroxypropyl)uridine (IIIg) and its tetrabenzoate XVI.Compounds XI and XVI on reaction with elemental fluorine in acetic acid afforded benzoyl derivatives of 5'-O-alkyl-5-fluorouridines XVIIa-XVIIe and XIX which were methanolyzed to give 5'-O-alkyl-5-fluorouridines II.This procedure afforded 5'-O-methyl (IIa), ethyl (IIb), n-butyl (IIc), n-hexyl (IId), n-octyl (IIe), and (RS)-(2,3-dihydroxypropyl) (IIf) derivatives of 5-fluorouridine.None of the compounds II exhibited antibacterial effect on Escherichia coli B or antiviral activity against HSV-1, HSV-2, vaccinia virus or vesicular stomatitis viruses.Compounds IIc,d,e suppressed the growth of L 1210 mice leukemic cells at concentrations of 10-5 to 10-6 mol l-1; the 5'-O-n-butyl derivative IIc has the highest activity (ID50 2.8 μmol l-1) but does not prolong the life span of L 1210 leukemia bearing mice following repeated daily doses of 80 mg/kg.
- Holy, Antonin,Koenig, Joachim,Vesely, Jiri,Cech, Dieter,Votruba, Ivan,Clercq, Erik de
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p. 1589 - 1608
(2007/10/02)
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- Conversion of Thiocarbonyl into Carbonyl in Uracil, Uridine, and Escherichia coli Transfer RNA using Hypervalent Iodine Oxidation
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2-Thiouracil, 5-, and 6-methyl-2-thiouracil were converted into uracil, 5-, and 6-methyluracil by PhIO in acetone; the 4-thiouridine site in tRNA was transformed to uridine by PhI(OH)OSO2C6H4Me-p at pH 4.0.
- Moriarty, Robert M.,Prakash, Indra,Clarisse, Diana E.,Penmasta, Raju,Awasthi, Alok K.
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p. 1209 - 1210
(2007/10/02)
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- 17O NMR of Nucleosides. 3 - Chemical Shifts of Substituted Uridines and Ribothymidines
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Uridine and ribothymidine derivatives, bearing different substituents at C-5 and enriched (Ca 50percent) with 17O in the O-4 and O-2 carbonyls, have been studied via 17O NMR in both acetonitrile and aqueous solvents.The solvent shift differences between acetonitrile and water at O-4 (30-42 ppm) and O-2 (13-16 ppm) vary significantly from each other, but the chemical shift changes induced by changing the substituent at C-5 correlated well only with the O-4 shifts and the electron-withdrawing ability of the substituent.Examination of the 17O shifts of model compounds reconfirms the predominance of keto tautomers for both carbonyls.The significance of the solvent shifts and substituent shifts are discussed with respect to the electronic structure of the nucleoside base rings, and with respect to the hydrogen-bonding abilities of the carbonyl groups.Other nucleoside derivatives studied include those in which the 17O enrichment is in the ring linking the base to the sugar moiety in a pyrimidine cyclonucleoside, in the sugar hydroxy groups and in the phosphodiester linkage of a highly strained ring system in a nucleoside cyclic monophosphate.
- Schwartz, Herbert M.,MacCoss, Malcolm,Danyluk, Steven S.
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p. 885 - 894
(2007/10/02)
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- Nucleoside Syntheses, XXII. Nucleoside Synthesis with Trimethylsilyl Triflate and Perchlorate as Catalysts
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The novel Lewis acids (CH3)3SiOSO2CF3 (5), (CH3)3SiOSO2C4F9 (6), and (CH3)3SiClO4 (4) are highly selective and efficient Friedel-Crafts catalysts for nucleoside formation from silylated heterocycles and peracylated sugars as well as for rearrangements of persilylated protected nucleosides.With basic silylated heterocycles these new catalysts give much higher yields of the natural N-1-nucleosides than with SnCl4.
- Vorbrueggen, Helmut,Krolikiewicz, Konrad,Bennua, Baerbel
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p. 1234 - 1255
(2007/10/02)
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- Nucleoside Syntheses, XXV. A New Simplified Nucleoside Synthesis
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The several steps of the Friedel-Crafts catalyzed silyl-Hilbert-Johnson nucleoside synthesis - silylation of the heterocyclic base, silylation of the perfluorosulfonic acids or its salts (if SnCl4 is not used as catalyst) and finally the nucleoside synthesis itself - can be combined to a simple one-step/one-pot reaction which generally affords nucleosides in high yields.
- Vorbrueggen, Helmut,Bennua, Baerbel
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p. 1279 - 1286
(2007/10/02)
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- Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions
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For the synthesis of y 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil (16), the precursor, 5′-O-benzoyl derivative (2),2 was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (4)2 was benzoylated to N3-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil (8) and its 3′,5′-O-isopropylidene analog (10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil (11) was first benzoylated to give 2′,5′-di-O-benzoate (12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product (12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil (15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.
- Sasaki,Minamoto,Hattori
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p. 2689 - 2694
(2007/10/09)
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