- Synthesis, Structural, and Conformational Analysis of 4′-C-Alkyl-2′-O-Ethyl-Uridine Modified Nucleosides
-
Sugar modifications have attracted much attention due to their potential structural and functional influence on therapeutic nucleic acids. Herein, we report the synthesis of dual modified 4′-C-azidomethyl-2′-O-ethyl-uridine (4′-AzM-2′-OEt?U) and 4′-C-aminomethyl-2′-O-ethyl-uridine (4′-AM-2′-OEt?U) nucleosides using linear multi-step synthesis (16 linear steps). Additionally, we report an alternative route for the synthesis of 2′-O-ethyl-uridine nucleoside which has been achieved in three steps with an overall yield of 40 %. X-ray structure of 4′-AzM-2′-OEt?U illustrates that the nucleoside adopts C2′-endo (South) conformation having a DNA-type glycosidic bond (χ) angle of ?116.01°. Computational studies revealed the C2′-endo and C4′-exo conformations for 4′-AzM-2′-OEt?U and 4′-AM-2′-OEt?U free nucleosides, respectively. The C4′-exo conformation in 4′-AM-2′-OEt?U free nucleoside is collectively stabilized by various non-covalent interactions between positively charged aminomethyl and 2′,3′-hydroxyl groups. Insights into the structural and conformational analysis of dual sugar modified nucleosides and oligonucleotides will be helpful in the rational design of modified nucleosides and therapeutic oligonucleotides.
- Nikam, Rahul R.,Harikrishna,Gore, Kiran R.
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p. 924 - 932
(2021/02/01)
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- 5’-Phosphorylation Increases the Efficacy of Nucleoside Inhibitors of the DNA Repair Enzyme SNM1A
-
Certain cancers exhibit upregulation of DNA interstrand crosslink repair pathways, which contributes to resistance to crosslinking chemotherapy drugs and poor prognoses. Inhibition of enzymes implicated in interstrand crosslink repair is therefore a promising strategy for improving the efficacy of cancer treatment. One such target enzyme is SNM1A, a zinc co-ordinating 5’–3’ exonuclease. Previous studies have demonstrated the feasibility of inhibiting SNM1A using modified nucleosides appended with zinc-binding groups. In this work, we sought to develop more effective SNM1A inhibitors by exploiting interactions with the phosphate-binding pocket adjacent to the enzyme's active site, in addition to the catalytic zinc ions. A series of nucleoside derivatives bearing phosphate moieties at the 5’-position, as well as zinc-binding groups at the 3’-position, were prepared and tested in gel-electrophoresis and real-time fluorescence assays. As well as investigating novel zinc-binding groups, we found that incorporation of a 5’-phosphate dramatically increased the potency of the inhibitors.
- Berney, Mark,Fay, Ellen M.,Manoj, Manav T,McGouran, Joanna F.
-
supporting information
(2022/01/13)
-
- Azido Functionalized Nucleosides Linked to Controlled Pore Glass as Suitable Starting Materials for Oligonucleotide Synthesis by the Phosphoramidite Approach
-
It has long been debated whether easily reducible azide groups can withstand the conditions of oligonucleotide synthesis by phosphoramidite chemistry. We have synthesized various 2′- and 3′-azido modified nucleosides and immobilized them on controlled pore glass (CPG) to be used as starting material for the synthesis of oligonucleotides (ONs) with 3′-terminal azide (attached to C2′ or C3′). In a model study, immobilized 3′-azidoadenosine was used as a starting block for the synthesis of a series of oligodeoxynucleotides (ODNs) of increasing length. Upon synthesis, the ODNs were enzymatically digested into monomers and analyzed by RP-HPLC. A peak corresponding to 3′-azidoadenosine was clearly identified in all samples. Quantitative analysis showed that 3′-azidoadenosine was present in nearly the expected ratio to deoxycytidine, which was used as an internal standard. Most importantly, the ratio remained the same for all three ODNs regardless of their length, demonstrating that a higher number of coupling cycles does not lead to higher degradation of the azide. Thus, 2′- or 3′-azido nucleosides attached to a solid support are excellent starting materials for the synthesis of oligonucleotides with 3′-terminal azide.
- Müggenburg, Frederik,Biallas, Alexander,Debiais, Mégane,Smietana, Michael,Müller, Sabine
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p. 6408 - 6416
(2021/11/30)
-
- Measurement of Angstrom to Nanometer Molecular Distances with 19F Nuclear Spins by EPR/ENDOR Spectroscopy
-
Spectroscopic and biophysical methods for structural determination at atomic resolution are fundamental in studies of biological function. Here we introduce an approach to measure molecular distances in bio-macromolecules using 19F nuclear spins and nitroxide radicals in combination with high-frequency (94 GHz/3.4 T) electron–nuclear double resonance (ENDOR). The small size and large gyromagnetic ratio of the 19F label enables to access distances up to about 1.5 nm with an accuracy of 0.1–1 ?. The experiment is not limited by the size of the bio-macromolecule. Performance is illustrated on synthesized fluorinated model compounds as well as spin-labelled RNA duplexes. The results demonstrate that our simple but strategic spin-labelling procedure combined with state-of-the-art spectroscopy accesses a distance range crucial to elucidate active sites of nucleic acids or proteins in the solution state.
- Meyer, Andreas,Dechert, Sebastian,Dey, Surjendu,H?bartner, Claudia,Bennati, Marina
-
supporting information
p. 373 - 379
(2019/11/22)
-
- UNA AMIDITES AND USES THEREOF
-
Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a disease which utilize a composition or
- -
-
Paragraph 0343; 0347
(2020/12/29)
-
- Addressing regio- And stereo-specificity challenges in the synthesis of nucleoside 2′,3′-cyclic monophosphate analogs-a rapid and facile synthesis of nucleoside-2′,3′-: O, O -phosphoro-thioate or -selenoate, and elucidation of the origin of the rare specificity
-
A new facile, rapid, stereo- and regio-selective one-pot synthesis of nucleoside-2′,3′-O,O-phosphorothioate and selenoate analogs has been developed. This method avoids the need for protection strategies and chiral reagents, chiral metal catalysts, or chiral separations. This synthetic method has been applied to all natural nucleosides (U/A/G/C/T). Furthermore, we have deciphered the origin of the stereo- and regio-selectivity of the reaction.
- Nassir, Molhm,Balaom, Lara,Fischer, Bilha
-
supporting information
p. 11633 - 11636
(2020/10/19)
-
- NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
-
Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.
- -
-
Paragraph 0453-0455
(2019/04/27)
-
- UDP-GlcNAc Analogues as Inhibitors of O-GlcNAc Transferase (OGT): Spectroscopic, Computational, and Biological Studies
-
A series of glycomimetics of UDP-GlcNAc, in which the β-phosphate has been replaced by either an alkyl chain or a triazolyl ring and the sugar moiety has been replaced by a pyrrolidine ring, has been synthesized by the application of different click-chemistry procedures. Their affinities for human O-GlcNAc transferase (hOGT) have been evaluated and studied both spectroscopically and computationally. The binding epitopes of the best ligands have been determined in solution by means of saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic, and computational results are in agreement, pointing out the essential role of the binding of β-phosphate. We have found that the loss of interactions from the β-phosphate can be counterbalanced by the presence of hydrophobic groups at a pyrroline ring acting as a surrogate of the carbohydrate unit. Two of the prepared glycomimetics show inhibition at a micromolar level.
- Ghirardello, Mattia,Perrone, Daniela,Chinaglia, Nicola,Sádaba, David,Delso, Ignacio,Tejero, Tomas,Marchesi, Elena,Fogagnolo, Marco,Rafie, Karim,van Aalten, Daan M. F.,Merino, Pedro
-
supporting information
p. 7264 - 7272
(2018/05/04)
-
- Tricyclanos: Conformationally constrained nucleoside analogues with a new heterotricycle obtained from a d-ribofuranose unit
-
A novel type of nucleoside analogue in which the sugar part is replaced by a new tricycle, 3,7,10-trioxa-11-azatricyclo[5.3.1.05,11]undecane has been prepared by substrate-controlled asymmetric synthesis. 1,5-Dialdehydes obtained from properly protected or unprotected uridine, ribothymidine, cytidine, inosine, adenosine and guanosine by metaperiodate oxidation reacted readily with tris(hydroxymethyl)aminomethane to provide the corresponding tricyclic derivatives with three new stereogenic centers. Through a double cyclisation cascade process the tricyclic compounds were obtained in good to high yields, with very high diastereoselectivity. Formation of one stereoisomer, out of the eight possible, was observed in all cases. The absolute configuration of the new stereotriad-containing tricyclic systems was aided by conventional NMR experiments followed by chemical shift calculations using an X-ray crystal structure as reference that was in good agreement with H-H distances obtained from a new ROESY NMR method. The synthesis was compatible with silyl, trityl and dimethoxytrityl protecting groups. A new reagent mixture containing ZnCl2, Et3SiH and hexafluoroisopropanol was developed for detritylation of the acid-sensitive tricyclano nucleosides.
- Kicsák, Máté,Mándi, Attila,Varga, Szabolcs,Herczeg, Mihály,Batta, Gyula,Bényei, Attila,Borbás, Anikó,Herczegh, Pál
-
supporting information
p. 393 - 401
(2018/02/06)
-
- Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
-
Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
- Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
-
supporting information
p. 3910 - 3917
(2017/03/27)
-
- Synthesis and in vitro growth inhibitory activity of novel silyl- and trityl-modified nucleosides
-
Seventeen silyl- and trityl-modified (5′-O- and 3′,5′-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentra
- Panayides, Jenny-Lee,Mathieu, Véronique,Banuls, Laetitia Moreno Y.,Apostolellis, Helen,Dahan-Farkas, Nurit,Davids, Hajierah,Harmse, Leonie,Rey, M.E. Christine,Green, Ivan R.,Pelly, Stephen C.,Kiss, Robert,Kornienko, Alexander,Van Otterlo, Willem A.L.
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p. 2716 - 2724
(2016/06/08)
-
- Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues
-
A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′-O-tritylated and the 5′-O-dimethoxytritylated 5-fluorouridine derivatives exerted potency against YFV. Interestingly in the series of purine analogues, the 5′O, N-bis-tritylated fludarabine derivative revealed strong inhibitory activity against DENV at μm concentrations, however significantly weaker potency against YFV.
- McGuigan, Christopher,Serpi, Michaela,Slusarczyk, Magdalena,Ferrari, Valentina,Pertusati, Fabrizio,Meneghesso, Silvia,Derudas, Marco,Farleigh, Laura,Zanetta, Paola,Bugert, Joachim
-
p. 227 - 235
(2016/07/07)
-
- An on-bead tailing/ligation approach for sequencing resin-bound RNA libraries
-
Nucleic acids possess the unique property of being enzymatically amplifiable, and have therefore been a popular choice for the combinatorial selection of functional sequences, such as aptamers or ribozymes. However, amplification typically requires known
- Wiesmayr, Anna,Fournier, Pierre,Jaeschke, Andres
-
scheme or table
p. e68
(2012/08/14)
-
- NOVEL PROTECTING GROUP FOR SYNTHESIZING RNA AND DERIVATIVE THEREOF
-
A protective group represented by the following general formula (I) (the oxygen atom attached with * represents oxygen atom of 2'-hydroxyl group of a ribonucleoside, a ribonucleotide or a derivative thereof, R1 and R2 both represent hydrogen atom, or represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; R3 and R4 represent hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; and R5 and R6 represent a halogen atom, a C1-6 halo-substituted alkyl group, cyano group, nitro group, or the like), which is stable under the reaction conditions of the nucleic acid synthetic cycles and has little steric hindrance, and can be removed under mild conditions using fluoride ions as a base.
- -
-
-
- Cationic nucleolipids as efficient siRNA carriers
-
We synthesized five novel uridine-based cationic nucleolipids, introducing basic amino acid residues at the 5′ position of uridine, through 1,3-dipolar cycloaddition, and hydrophobic alkyl moieties at the 2′ and 3′ positions, through carbamate linkages. T
- Yang, Hye Won,Yi, Jeong Wu,Bang, Eun-Kyoung,Jeon, Eun Mi,Kim, Byeang Hyean
-
scheme or table
p. 291 - 296
(2011/02/24)
-
- A U-tetrad stabilizes human telomeric RNA G-quadruplex structure
-
Telomeric repeat-containing RNA is a new noncoding RNA molecule recently discovered in mammalian cells. Here we report the structural features of human telomere RNA r(UAGGGU) in the presence of K+ and Na+. We demonstrated for the first time that a novel U-tetrad is formed at the 3- end of a parallel human telomeric RNA G-quadruplex. The U-tetrad dramatically stabilizes human telomeric RNA G-quadruplex structure, leading to an increase in melting temperature (Tm) of 29 °C. The U-tetrad-stabilized telomeric RNA G-quadruplex structure adds considerably to our understanding of the diversity of RNA G-quadruplex architectures. It shows that the structure of base "quartets" is important in RNA assembly. The structural information will be invaluable for understanding the function of human telomere RNA.
- Xu, Yan,Ishizuka, Takumi,Kimura, Takashi,Komiyama, Makoto
-
supporting information; experimental part
p. 7231 - 7233
(2010/08/05)
-
- A solvent free and selective method for preparation of triphenylmethyl ethers of alcohols and nucleosides
-
A very simple and efficient method is described for protection of alcohols and nucleosides with trityl(triphenylmethyl), mono and dimethoxytrityl chlorides in the presence of triethylamine under microwave irradiation. High selectivity was observed for tritylation of 5'-OH function of nucleosides.
- Zekri, Negar,Alamdari, Reza Fareghi,Khalafi-Nezhad, Ali
-
experimental part
p. 299 - 304
(2012/04/23)
-
- Efficient photoactivation of a Diels-Alderase ribozyme
-
Here we report the first example of a photoactivatable ribozyme which catalyzes a bimolecular reaction of two small organic molecules with multiple turnover, under control of a photo-cleavable protecting group by exploiting the structural significance of
- Nierth, Alexander,Singer, Marco,Jaeschke, Andres
-
experimental part
p. 7975 - 7977
(2011/01/04)
-
- An efficient and selective method for the preparation of triphenylmethyl ethers of alcohols and nucleosides
-
A very simple and efficient method is described for the protection of alcohols and nucleosides with benzyl monomethoxytrityl and benzyl dimethoxytrityl ethers in the presence of diethylazodicarboxylate and a catalytic amount of ceric triflate. High selectivity was observed for the tritylation of 5'-OH function of nucleosides.
- Zekri, Negar,Alamdari, Reza Fareghi
-
experimental part
p. 563 - 568
(2010/08/05)
-
- Novel selectivity in carbohydrate reactions, IV: DABCO-mediated regioselective primary hydroxyl protection of carbohydrates
-
An efficient procedure for the regioselective tritylation of primary hydroxyl group of aldohexopyranosides and nucleosides using trityl chloride in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in dichloromethane has been developed. Subsequent acetylation of the tritylated products in the same pot has been made possible, thereby providing an efficient route to the fully protected carbohydrate derivatives that can be discriminated chemoselectively.
- Gadakh, Bharat Kacheshwar,Patil, Premanand Ramrao,Malik, Satish,Kartha, K. P. Ravindranathan
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experimental part
p. 2430 - 2438
(2009/12/03)
-
- RNA interference in mammalian cells by siRNAs modified with morpholino nucleoside analogues
-
siRNAs modified with morpholino nucleoside analogues were synthesized and their biological properties were examined in details. The gene silence abilities of modified siRNAs were correlated to the positions of the modifications, some of which appeared to
- Zhang, Nan,Tan, Chunyan,Cai, Puqin,Zhang, Peizhuo,Zhao, Yufen,Jiang, Yuyang
-
experimental part
p. 2441 - 2446
(2009/07/25)
-
- Application of ball milling technology to carbohydrate reactions: I. Regioselective primary hydroxyl protection of hexosides and nucleoside by planetary ball milling
-
Dry ball milling of hexosides with trityl chloride in the presence of DABCO or Na2CO3 has been found to result in their complete conversion to the respective 6-O-trityl ethers. Further wet grinding of the reaction mixture with Ac2O in the presence of DMAP led to the respective fully protected hexosides in good to excellent yields after isolation. It has been found to be an effective one-pot two-step synthesis under solvent-free condition. The speed of homogenization has been shown to highly influence the rate and outcome of the reaction, and commercially available planetary ball mill has been proved to be very convenient for carrying out the reaction under standardized and reproducible conditions.
- Patil, Premanand Ramrao,Kartha, K.P. Ravindranathan
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p. 279 - 293
(2008/12/21)
-
- Synthesis and biological evaluation of novel selenonucleosides
-
A series of novel selenonucleoside analogues with 1,4-oxaselenane as the carbohydrate fragment has been synthesized from their corresponding dimesylated seconucleosides treated with NaHSe solution and subsequent deprotection. The synthesized selenonucleos
- Chen, Yao,Peng, Yingdan,Zhang, Jiancun,Fu, Lei
-
p. 1001 - 1008
(2008/12/22)
-
- A base-labile group for 2′-OH protection of ribonucleosides: A major challenge for RNA synthesis
-
A base-labile group for 2'-OH protection of ribonucleosides was investigated. The solid support was dried by blowing argon through a DNA synthesizer and was first treated with 10% anhydrous piperidine in CH 3CN at room temperature for 15 minutes to eliminate cyanoethyl groups from phosphates. The piperidine solution was removed from the column and the solid support was washed with CH3CN. The three ammoniacal eluates were collected in a screw-capped glass vial and were left at room temperature for a further 1.5 hours to completely deprotect nucleobases and 2'-hydroxyl groups. The fully deprotected oligonucleotide was transferred to a 50 mL round-bottomed flask and isopropylamine was added to the solution before evaporation to dryness. It was observed that PivOM method provides highly pure RNA without any additional desalting step.
- Lavergne, Thomas,Bertrand, Jean-Remi,Vasseur, Jean-Jacques,Debart, Francoise
-
scheme or table
p. 9135 - 9138
(2009/10/01)
-
- 2'-HYDROXYL-MODIFIED RIBONUCLEOSIDE DERIVATIVE
-
Provided is a ribonucleoside derivative represented by General Formula (I): (wherein R1 represents a hydrogen atom or the like, R2 represents a hydrogen atom or the like, R3 represents a methyl group or the like, and B represents a nucleic acid base residue optionally having a protecting group or a modifying group). An RNA containing this ribonucleoside derivative shows excellent hybridization ability and resistance to nuclease.
- -
-
Page/Page column 17
(2009/01/24)
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- Solid-phase synthesis and on-column deprotection of RNA from 2′- (and 3′-) O-Levulinated (Lv) ribonucleoside monomers
-
(Chemical Equation Presented) The solid-phase synthesis of oligoribonucleotides derived from ribonucleosides esterified at the 2′ (or 3′-) position with the levulinyl (Lv) group is described. The oligomers can be released from the solid support as 2′-O-Lv
- Lackey, Jeremy G.,Sabatino, David,Damha, Masad J.
-
p. 789 - 792
(2008/01/27)
-
- Functional synthetic molecules and macromolecules for gene delivery
-
The present invention describes a synthetic non-viral vector composition for gene therapy and the use of such compositions for in vitro, ex vivo and/or in vivo transfer of genetic material. The invention proposes a pharmaceutical composition containing 1) a non-cationic amphiphilic molecule or macromolecule and its use for delivery of nucleic acids or 2) a cationic amphiphilic molecule or macromolecule that transforms from a cationic entity to an anionic, neutral, or zwitterionic entity by a chemical, photochemical, or biological reaction and its use for delivery of nucleic acids. Moreover this invention describes the use of these non-viral vector compositions in conjunction with a surface to mediate the delivery of nucleic acids. An additional embodiment is the formation of a hydrogel with these compositions and the use of this hydrogel for the delivery of genetic material. A further embodiment of this invention is the use of a change in ionic strength for the delivery of genetic material.
- -
-
Page/Page column 44-45; 52; 74
(2008/06/13)
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- Supramolecular assemblies of DNA with neutral nucleoside amphiphiles
-
A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-
- Barthelemy, Philippe,Prata, Carla A. H.,Filocamo, Shaun F.,Immoos, Chad E.,Maynor, Benjamin W.,Hashmi, S. A. Nadeem,Lee, Stephen J.,Grinstaff, Mark W.
-
p. 1261 - 1263
(2008/09/17)
-
- A new RNA synthetic method with a 2′-O-(2-cyanoethoxymethyl) protecting group
-
(Chemical Equation Presented) A novel method for the synthesis of RNA oligomers with 2-cyanoethoxymethyl (CEM) as the 2′-hydroxyl protecting group has been developed. The new method allows the synthesis of oligoribonucleotides with an efficiency and final
- Ohgi, Tadaaki,Masutomi, Yutaka,Ishiyama, Kouichi,Kitagawa, Hidetoshi,Shiba, Yoshinobu,Yano, Junichi
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p. 3477 - 3480
(2007/10/03)
-
- Tetrabutylammonium bromide: An efficient media for dimethoxytritylation of the 5'-hydroxyl function of nucleosides
-
An efficient procedure for selective dimethoxytritylation of the 5'-hydroxyl function of nucleosides in the presence of DABCO in molten tetrabutylammonium bromide is described. The methodology is very practical, environmentally benign and produced the desired product in less than 5 min by grinding in a hot mortar. In addition, the effects of the room temperature ionic liquid (1-butyl-3-methylimidazolium chloride) and microwave irradiation on this system were also studied and the results showed that depurination of the nucleosides occurred under microwave irradiation.
- Khalafi-Nezhad, Ali,Mokhtari, Babak
-
p. 6737 - 6739
(2007/10/03)
-
- Synthesis of acyclic bis-vinyl pyrimidines: A general route to d4T via metathesis
-
Unsaturated acyclic pyrimidine analogues, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}uracil, 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}thymine and 1-{1-[1-(hydroxymethyl)prop-2-enyloxy]prop-2-enyl}cytosine having two asymmetric carbon atoms have been prepared in good yield starting from uridine and 5-methyluridine. The bis-vinyl thymine derivative underwent ring closure metathesis to give d4T, thus providing a novel synthesis of this compound.
- Ewing,Gla?on,Mackenzie,Postel,Len
-
p. 941 - 945
(2007/10/03)
-
- Reliable chemical synthesis of oligoribonucleotides (RNA) with 2′-O-[(triisopropylsilyl)oxy]methyl(2′-O-tom)-protected phosphoramidites
-
A method for the introduction of the 2′-O-[(triisopropylsilyl)oxy]methyl (=tom) group into N-acetylated, 5′-O-dimethoxytritylated ribonucleosides is presented. The corresponding 2′-O-tom-protected phosphoramidite building blocks were obtained in pure form and were successfully employed for the routine synthesis of oligoribonucleotides on DNA synthesizers. Under DNA coupling conditions (2.5 min coupling time for a 1.5-μmol synthesis scale) and with 5-(benzylthio)-1H-tetrazole (BTT) as activator, 2′-O-tom-protected phosphoramidites exhibited average coupling yields >99.4%. The combination of N-acetyl and 2′-O-tom protecting groups allowed a reliable and complete two-step deprotection, first with MeNH2 in EtOH/H2O and then with Bu4NF in THF, without concomitant destruction of the product RNA sequences.
- Pitsch, Stefan,Weiss, Patrick A.,Jenny, Luzi,Stutz, Alfred,Wu, Xiaolin
-
p. 3773 - 3795
(2007/10/03)
-
- Synthetic studies of the tunicamycin antibiotics. Preparation of (+)-tunicaminyluracil, (+)-tunicamycin-V, and 5′-epi-tunicamycin-V
-
A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V). Key features of the synthesis include (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a performed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly covergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.
- Myers, Andrew G.,Gin, David Y.,Rogers, Daniel H.
-
p. 4697 - 4718
(2007/10/02)
-
- General Method for the Synthesis of 2'-Azido-2',3'-dideoxynucleosides by the Use of -Hydride Shift and &β-Elimination Reactions
-
The title nucleoside (16U, C, G and H) were synthesized from pyrimidine and purine ribonucleosides in about 30percent overall yield in 6 steps via key intermediates, protected 3'-deoxy-arabino-nucleosides, which were obtained by deoxygenative -hydrid
- Kawana, Masajiro,Kuzuhara, Hiroyoshi
-
p. 469 - 478
(2007/10/02)
-
- 1-(2,3-anhydro-β-D-lyxofuranosyl)cytosine derivatives as potential inhibitors of the human immunodeficiency virus
-
We report here that 1-(2,3-anhydro-β-D-lyxofuranosyl)cytosine has activity against the human immunodeficiency virus in vitro. A number of 2',3'-anhydro-β-D-lyxofuranosyl nucleoside derivatives were prepared, but none had the activity of the title compound. New efficient procedures were developed for the synthesis of 3'-deoxy-3'-alkyl- and 3'-deoxy-β-D-arabinosylpyrimidine derivatives.
- Webb,Mitsuya,Broder
-
p. 1475 - 1479
(2007/10/02)
-
- New catalists and procedures for the dimethoxytritylation and selective silylation of ribonucleosides
-
Procedures have been developed for the selective formation of (a) 2',5'-silylated ribonucleosides and (b) 3',5'-silylated ribonucleosides.These procedures also permit the selective silylation at either the 2'- or 3'-position of dimethoxytritylated ribonuc
- Hakimelahi, Gholam H.,Proba, Zbigniew A.,Ogilvie, Kelvin K.
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p. 1106 - 1113
(2007/10/02)
-