15176-29-1Relevant articles and documents
Importance of 3′-hydroxyl group of the nucleosides for the reactivity of thymidine phosphorylase from Escherichia coli
Hatano, Akihiko,Harano, Aiko,Kirihara, Masayuki
, p. 232 - 233 (2006)
Thymidine phosphorylase in phosphate buffer catalyzed the conversion of thymidine to unnatural nucleosides. The 3′-OH, but not the 5′-OH of ribosyl moiety is necessary to be recognized as a substrate. Thus 3′-deoxythymidine could not convert to 5-fluorouracil-2′,3′- dideoxyribose. However, 5′-deoxythymidine was converted to 5-fluorouracil-2′,5′-dideoxyribose. Copyright
Synthesis of 5-ethylpyrimidine nucleoside analogs
Takenaka, Keiko,Muraoka, Masako,Tsuji, Tadakazu
, p. 669 - 673 (1997)
This paper describes the synthesis of acyclic, cyclic, and deoxy sugar nucleosides of 5-ethylpyrimidine, i.e., i) 1-(2-hydroxyethoxymethyl), 1-(2-methoxyethoxymethyl), and 1-ethoxyethyl derivatives of 5-ethyluracil and 5-ethylcytosine, ii) 5-ethyl-1-(tetrahydro-2H-pyran-2-yl)- and -1-(tetrahydrofuran-2-yl)uracils, and iii) 5-ethyl-2'-deoxyuridine.
Use of Nucleoside Phosphorylases for the Preparation of Purine and Pyrimidine 2′-Deoxynucleosides
Drenichev, Mikhail S.,Alexeev, Cyril S.,Kurochkin, Nikolay N.,Mikhailov, Sergey N.
, p. 305 - 312 (2018)
Enzymatic transglycosylation – the transfer of the carbohydrate moiety from one heterocyclic base to another – is being actively developed and applied for the synthesis of practically important nucleosides. This reaction is catalyzed by nucleoside phosphorylases (NPs), which are responsible for reversible phosphorolysis of nucleosides to yield the corresponding heterocyclic bases and monosaccharide 1-phosphates. We found that 7-methyl-2′-deoxyguanosine (7-Me-dGuo) is an efficient and novel donor of the 2-deoxyribose moiety in the enzymatic transglycosylation for the synthesis of purine and pyrimidine 2′-deoxyribonucleosides in excellent yields. Unlike 7-methylguanosine, its 2′-deoxy derivative is dramatically less stable. Fortunately, we have found that 7-methyl-2′-deoxyguanosine hydroiodide may be stored for 24 h in Tris-HCl buffer (pH 7.5) at room temperature without significant decomposition. In order to optimize the reagent ratio, a series of analytical transglycosylation reactions were conducted at ambient temperature. According to HPLC analysis of the transglycosylation reactions, the product 5-ethyl-2′-deoxyuridine (5-Et-dUrd) was obtained in high yield (84–93%) by using a small excess (1.5 and 2.0 equiv.) of 7-Me-dGuo over 5-ethyluracil (5-Et-Ura) and 0.5 equiv. of inorganic phosphate. Thymidine is a less effective precursor of α-d-2-deoxyribofuranose 1-phosphate (dRib-1p) compared to 7-Me-dGuo. We synthesized 2′-deoxyuridine, 5-Et-dUrd, 2′-deoxyadenosine and 2′-deoxyinosine on a semi-preparative scale using the optimized reagent ratio (1.5:1:0.5) in high yields. Unlike other transglycosylation reactions, the synthesis of 2-chloro-2′-deoxyadenosine was performed in a heterogeneous medium because of the poor solubility of the initial 2-chloro-6-aminopurine. Nevertheless, this nucleoside was prepared in good yield. The developed enzymatic procedure for the preparation of 2′-deoxynucleosides may compete with the known chemical approaches. (Figure presented.).
One-pot approach to functional nucleosides possessing a fluorescent group using nucleobase-exchange reaction by thymidine phosphorylase
Hatano, Akihiko,Kurosu, Masayuki,Yonaha, Susumu,Okada, Munehiro,Uehara, Sanae
, p. 6900 - 6905 (2013/10/08)
Herein, we describe β-selective coupling between a modified uracil and a deoxyribose to produce functionalized nucleosides catalyzed by thymidine phosphorylase derived from Escherichia coli. This enzyme mediates nucleobase-exchange reactions to convert unnatural nucleosides possessing a large functional group such as a fluorescent molecule, coumarin or pyrene, linked via an alkyl chain at the C5 position of uracil. 5-(Coumarin-7-oxyhex-5- yn)uracil (C4U) displayed 57.2% conversion at 40% DMSO concentration in 1.0 mM phosphate buffer pH 6.8 to transfer thymidine to an unnatural nucleoside with C4U as the base. In the case of using 5-(pyren-1-methyloxyhex-5-yn)uracil (P4U) as the substrate, TP also could catalyse the reaction to generate a product with a very large functional group at 50% DMSO concentration (21.6% conversion). We carried out docking simulations using MF myPrest for the modified uracil bound to the active site of TP. The uracil moiety of the substrate binds to the active site of TP, with the fluorescent moiety linked to the C5 position of the nucleobase located outside the surface of the enzyme. As a consequence, the bulky fluorescent moiety binding to uracil has little influence on the coupling reaction.
Continuous flow photochemistry for the rapid and selective synthesis of 2′-deoxy and 2′,3′-dideoxynucleosides
Shen, Bo,Jamison, Timothy F.
, p. 157 - 164 (2013/04/10)
A new photochemical flow reactor has been developed for the photo-induced electron-transfer deoxygenation reaction to produce 2′-deoxy and 2′,3′-dideoxynucleosides. The continuous flow format significantly improved both the efficiency and selectivity of the reaction, with the streamlined multi-step sequence directly furnishing the highly desired unprotected deoxynucleosides.
Nucleoside analogue phosphates for topical use
-
, (2008/06/13)
Compositions for topical use in herpes virus infections comprising anti-herpes nucleoside analogue phosphate esters, such as acyclovir monophosphate, acyclovir diphosphate, and acyclovir triphosphate which show increased activity against native strains of herpes virus as well as against resistant strains, particularly thymidine kinase negative strains of virus. Also disclosed are methods for treatment of herpes infections with nucleoside phosphates. Anti-herpes nucleoside analogues phosphate esters include the phosphoramidates and phosphothiorates, as well as polyphosphates comprising C and S bridging atoms.
SYNTHESIS OF 2-DEOXY-β-D-RIBONUCLEOSIDES AND2,3-DIDEOXY.β-D-PENTOFURANOSIDES ON IMMOBILIZED BACTERIAL CELLS
Votruba, Ivan,Holy, Antonin,Dvorakova, Hana,Guenter, Jaroslav,Hockova, Dana,et al.
, p. 2303 - 2330 (2007/10/02)
Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs.All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N9-isomers in the purine and N1-isomers in the pyrimidine series.Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety.The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N7-nitrogen atom.On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives.Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed.The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-deoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-deoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.
Synthesis and antiviral activity of novel 5-(1-azido-2-haloethyl) and 5- (1-azido-, amino-, or methoxyethyl) analogs of 2'-deoxyuridine
Kumar,Wiebe,Knaus
, p. 2470 - 2474 (2007/10/02)
A new class of 5-(1-azido-2-haloethyl)-2'-deoxyuridines 3a-c was synthesized by the regiospecific addition of XN3 (X = I, Br, Cl) to the vinyl substituent of 5-vinyl-2'-deoxyuridine. Treatment of the 5-(1-azido-2- iodoethyl) compound (3a) with H2 and 10% Pd/C yielded the 5-(1-azidoethyl) (4) and 5-(1-aminoethyl) (5) derivatives of 2'-deoxyuridine. A similar hydrogenation of 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (1f) afforded the 5-(1-methoxyethyl) analog 6. The 5-(1-azido-2-haloethyl)-2'-deoxyuridines 3a- c exhibited in vitro antiviral activity against HSV-1, HSV-2, VZV, and EBV, but they were inactive against HCMV. In this group of compounds, the activity order was Cl ≥ I > Br against HSV-1 and Br ≥ Cl > I against HSV-2. A halogen atom in the 5-(1-azido-2-haloethyl) moiety 3a-c is an essential requirement since the 5-(1-azidoethyl) analog 4 was inactive, except for weak antiviral activity against VZV. Although the 5-(1-aminoethyl)-2'- deoxyuridine·HI (5) was inactive against HSV-1 and HSV-2, the 5-(1- methoxyethyl) compound 6 was equiactive to 5-ethyl-2'-deoxyuridine (EDU) against both HSV-1 and HSV-2 and 7-fold and 12-fold less active against HCMV relative to EDU and ganciclovir, respectively. All compounds investigated (3- 6) exhibited low host cell cytotoxicity (IC50 > 118 μM) and inhibited cell proliferation only at high concentrations (IC50 > 76 μM).
PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF ORGANOSTANNANES WITH NUCLEOSIDE HALIDES
Hassan, Mohamed Ezeldin
, p. 1944 - 1948 (2007/10/02)
A general reaction is described for the synthesis of C-5 substituted nucleosides through the coupling of organostannanes with nucleoside-palladium intermediate derived in situ from 5-iodouridine (or 5-iodo-2'-deoxyuridine) and .The reaction was used for the synthesis of C-5 aryl, heteroaryl, vinyl, allyl and alkyl substituted nucleosides.
Nucleic Acid Related Compounds. 39. Efficient Conversion of 5-Iodo to 5-Alkynyl and Derived 5-Substituted Uracil Bases and Nuleosides
Robins, Morris J.,Barr, Philip J.
, p. 1854 - 1862 (2007/10/02)
Coupling of terminal alkynes with 5-iodo-1-methyl-uracil and 5-iodouracil nucleosides (protected as their p-toluyl esters) proceeded in high yields in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I)iodide in warm triethylamine.Several of the subsequently deprotected 5-alkynyl-2'-deoxyuridines, including the parent 5-ethynyl-2'-deoxyuridine, had antiviral activity, and their 5'-monophosphates inhibited thymidylate synthetase.Hydrogenation of the 5-alkynyl side chain can be controlled to give (Z)-5-alkenyl- or the saturated 5-alkyl-2'-deoxyuridines.This provides a stereocontrolled route to the known 5-ethyl-and 5-n-hexyl-2'-deoxyuridines as well as (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU).Hydration of the triple bond gave the corresponding uracil-5-alkanone products in favorable cases.
