26929-65-7Relevant articles and documents
Synthesis of 2′-aminouridine derivatives as an organocatalyst for Diels-Alder reaction?
Wakamatsu, Hideaki,Itoh, Moeko,Natori, Yoshihiro,Yoshimura, Yuichi
, p. 365 - 383 (2020)
To develop a novel asymmetric organocatalyst based on a ribonucleoside skeleton, we designed and synthesized 2′-aminouridine derivatives. The synthesized 2′-aminouridines having bulky substituents at both base and sugar moieties could catalyze the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene. However, the optical purities of the resulting products were unexpectedly low.
Efficient synthesis of 2'-amino-2'-deoxypyrimidine 5'- triphosphates
McGee,Vargeese,Zhai,Kirschenheuter,Settle,Siedem,Pieken
, p. 1329 - 1339 (1995)
The synthesis of 2'-amino-2'-deoxypyrimidine 5'-triphosphates is described. The 2'-amino-2'-deoxyuridine 5'-triphosphate is obtained from uridine in four steps with 25% overall yield. The 2'-amino-2'-deoxycytidine 5'-triphosphate is obtained from uridine in seven steps with 13% overall yield.
Site of azido substitution in the sugar moiety of azidopyrimidine nucleosides influences the reactivity of aminyl radicals formed by dissociative electron attachment
Mudgal, Mukesh,Dang, Thao P.,Sobczak, Adam J.,Lumpuy, Daniel A.,Dutta, Priya,Ward, Samuel,Ward, Katherine,Alahmadi, Moaadh,Kumar, Anil,Sevilla, Michael D.,Wnuk, Stanislaw F.,Adhikary, Amitava
, p. 11357 - 11370 (2020)
In this work, electron-induced site-specific formation of neutral π-type aminyl radicals (RNH·) and their reactions with pyrimidine nucleoside analogs azidolabeled at various positions in the sugar moiety, e.g., at 2′-, 3′-, 4′-, and 5′- sites along with a model compound 3-azido-1-propanol (3AZPrOH), were investigated. Electron paramagnetic resonance (EPR) studies confirmed the site and mechanism of RNH· formation via dissociative electron attachment-mediated loss of N2 and subsequent facile protonation from the solvent employing the 15N-labeled azido group, deuterations at specific sites in the sugar and base, and changing the solvent from H2O to D2O. Reactions of RNH· were investigated employing EPR by warming these samples from 77 K to ca. 170 K. RNH· at a primary carbon site (5′-azido-2′,5′-dideoxyuridine, 3AZPrOH) facilely converted to a σ-type iminyl radical (R=N·) via a bimolecular H-atom abstraction forming an α-azidoalkyl radical. RNH· when at a secondary carbon site (e.g., 2′-azido-2′-deoxyuridine) underwent bimolecular electrophilic addition to the C5=C6 double bond of a proximate pyrimidine base. Finally, RNH· at tertiary alkyl carbon (4′-azidocytidine) underwent little reaction. These results show the influence of the stereochemical and electronic environment on RNH· reactivity and allow the selection of those azidonucleosides that would be most effective in augmenting cellular radiation damage.
An Improved Synthesis of 2'-Azido-2'-Deoxyuridine
Kirschenheuter, Gary P.,Zhai, Yansheng,Pieken, Wolfgang A.
, p. 8517 - 8520 (1994)
A high yield process for the conversion of 2,2'-cyclouridine to 2'-azido-2'-deoxyuridine was developed.The procedure utilizes a lithium azide:TMEDA complex generated in situ from the reaction of lithium fluoride and azidotrimethylsilane in DMF with TMEDA added as a co-solvent.
Molecular modeling of the human P2Y2 receptor and design of a selective agonist, 2′-amino-2′-deoxy-2-thiouridine 5′-triphosphate
Ivanov, Andrei A.,Ko, Hyojin,Cosyn, Liesbet,Maddileti, Savitri,Besada, Pedro,Fricks, Ingrid,Costanzi, Stefano,Harden, T. Kendall,Van Calenbergh, Serge,Jacobson, Kenneth A.
, p. 1166 - 1176 (2007)
A rhodopsin-based homology model of the nucleotide-activated human P2Y 2 receptor, including loops, termini, and phospholipids, was optimized with the Monte Carlo multiple minimum conformational search routine. Docked uridine 5′-triphosphate (UTP) formed a nucleobase π-π complex with conserved Phe3.32. Selectivity-enhancing 2′-amino-2′-deoxy substitution interacted through π-hydrogen-bonding with aromatic Phe6.51 and Tyr3.33. A "sequential ligand composition" approach for docking the flexible dinucleotide agonist Up4U demonstrated a shift of conserved cationic Arg3.29 from the UTP γ position to the δ position of Up4U and Up4 ribose. Synthesized nucleotides were tested as agonists at human P2Y receptors expressed in 1321N1 astrocytoma cells. 2′-Amino and 2-thio modifications were synergized to enhance potency and selectivity; compound 8 (EC50 = 8 nM) was 300-fold P2Y 2-selective versus P2Y4. 2′-Amine acetylation reduced potency, and trifluoroacetylation produced intermediate potency. 5-Amino nucleobase substitution did not enhance P2Y2 potency through a predicted hydrophilic interaction possibly because of destabilization of the receptor-favored Northern conformation of ribose. This detailed view of P2Y 2 receptor recognition suggests mutations for model validation.
RELEASABLE CONJUGATES
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Page/Page column 173; 174, (2018/09/28)
The present application provides compounds of Formula (B), or pharmaceutically acceptable salts thereof, wherein D is a residue of a biologically active drug, which underdo hydrolysis under physiological conditions to release the biologically active drug and which are useful in the treatment of disorders that could be beneficially treated with the drug.
Regioselective Mitsunobu Reaction of Partially Protected Uridine
Szlenkier, Maurycy,Kamel, Karol,Boryski, Jerzy
, p. 410 - 425 (2016/08/05)
Mitsunobu reaction of partially acylated uridine proceeds with high regioselectivity for intramolecular SN2 anhydro linkage closuring. Under the reaction conditions, an isomeric mixture of diacyl uridine derivatives with either free 2′- or 3′-hydroxyl group was transformed into a single cyclonucleosidic product, 2,2′-anhydro-3′,5′-di-O-acyluridine. This paper presents a possible mechanism of the reactions, the explanation of observed phenomenon based on semiempirical and density functional theory (DFT) calculations and possible utility of this synthetic pathway.
Cu(I)-catalyzed efficient synthesis of 2'-triazolo-nucleoside conjugates
Mathur,Rana,Olsen,Parmar,Prasad
, p. 701 - 710 (2015/05/13)
A small library of thirty-two 2'-triazolyl uridine and 2'-triazolyl-5-methyluridine has been synthesized by Cu(I)-catalyzed condensation of 2'-azido-2'-deoxyuridine and 2'-azido-2'-deoxy-5-methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo-nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of 1H NMR, 13C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.
Design and synthesis of 2′-Deoxy-2′-[(1,2,3)Triazol-1-Yl]uridines using click chemistry approach
Kumar, Surender
, p. 371 - 378 (2015/05/05)
A series of novel nucleosides bearing a 1,2,3-triazole moiety at the 2′-position of the sugar moiety has been synthesized starting from 2′-azidouridine and using the copper (I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction. The reactions proceeded in overall yield of 52-82% and gave almost exclusively the 1,4-disubstituted 1,2,3-triazoles. The 2′-azidouridine was synthesized from uridine in two steps, and reacted with a variety of differently substituted alkynes to give the desired 2′-triazole-substituted uridine derivatives.
Unprecedented C-selective interstrand cross-linking through in situ oxidation of furan-modified oligodeoxynucleotides
De Beeck, Marieke Op,Madder, Annemieke
supporting information; experimental part, p. 796 - 807 (2011/04/15)
Chemical reagents that form interstrand cross-links have been used for a long time in cancer therapy. They covalently link two strands of DNA, thereby blocking transcription. Cross-link repair enzymes, however, can restore the transcription processes, causing resistance to certain anti-cancer drugs. The mechanism of these cross-link repair processes has not yet been fully revealed. One of the obstacles in this study is the lack of sufficient amounts of well-defined, stable, cross-linked duplexes to study the pathways of cross-link repair enzymes. Our group has developed a cross-link strategy where a furan moiety is incorporated into oligodeoxynucleotides (ODNs). These furan-modified nucleic acids can form interstrand crosslinks upon selective furan oxidation with N-bromosuccinimide.We here report on the incorporation of the furan moiety at the 20-position of a uridine through an amido or ureido linker. The resulting modified ODNs display an unprecedented selectivity for cross-linking toward a cytidine opposite the modified residue, forming one specific cross-linked duplex, which could be isolated in good yield. Furthermore, the structure of the formed cross-linked duplexes could be unambiguously characterized.
