14057-18-2Relevant academic research and scientific papers
Enzymatic regioselective and complete deacetylation of two arabinonucleosides
Sabaini, Maria B.,Zinni, Maria A.,Mohorcic, Martina,Friedrich, Jozefa,Iribarren, Adolfo M.,Iglesias, Luis E.
, p. 225 - 229 (2010)
Candida antarctica lipase B (CAL-B)-catalysed regioselective deacetylation of 2′,3′,5′-tri- O-acetyl-1-β- d-arabinofuranosyluracil (1) and 2′,3′,5′-tri- O-acetyl-9-β- d-arabinofuranosyladenine (2) was studied. The choice of the reaction medium allowed the regioselective formation of products bearing different degree of acetylation: in isopropanol, CAL-B catalysed the formation of the corresponding 2′- O-acetylated arabinonucleosides, while hydrolyses afforded the 2′,3′-di- O-acetylated products. In particular, the procedure herein described allows a simple and efficient preparation of the reported vidarabine prodrug 2′,3′-di- O-acetyl-9-β- d-arabinofuranosyladenine, avoiding the utilisation of protective groups. Moreover, to achieve full deacetylation of the assayed substrates, a set of commercial hydrolases and fungal keratinases from Doratomyces microsporus (DMK) and Paecilomyces marquandii (PMK) were tested. While only PMK and DMK catalysed the quantitative complete deacetylation of 1, DMK accomplished full deacetylation of 2 in shorter time than the other assayed enzymes.
Synthesis of 5-radioiodoarabinosyl uridine analog for probing the HSV-1 thymidine kinase gene
Lin, Kun-I.,Chiang, Li-Wu,Wu, Chien-Hung,Chen, Shao-Wei,Yu, Chung-Shan
, p. 563 - 568 (2007)
Tumor cells transduced with herpes simplex virus thymidine kinase gene have been intensively applied to the field of positron emission tomography via imaging of its substrate. As a pilot synthesis approach, a facile preparation of 5-[125I]iodoarabinosyl uridine starting from commercially available uridine is reported herein.
Nucleic Acid Related Compounds. 65. New Syntheses of 1-(β-D-Arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from Vinylsilane Precursors. Radioiodine Uptake as a Marker for Thymidine Kinase Positive Herpes Viral Infections
Robins, Morris J.,Manfredini, Stefano,Wood, Steven G.,Wanklin, R. James,Rennie, Bruce A.,Sacks, Stephen L.
, p. 2275 - 2280 (1991)
(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-iodouracil (3) to give 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-uracil (4).Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-β-D-arabinofuranosyl)-5(Z)-uracil (5).Treatment of 5 with iodine monochloride (or sodium iodide/phenyliodine(III) dichloride) in benzene gave 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (7), whereas polar solvents favored the (Z)-iodovinyl isomer 8.Deacetylation of 7gave 1-β-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU,9).A microscale in situ synthesis with Na*I gave IVAraU.Treatment of HSV-infected cells with IVAraU resulted in virus-dependent uptake associated with nucleoside phosphorylation by wild type or acyclovir-resistant DNA polymerase mutants (but not with TK-HSV-1 mutants).Uptake was virus-inoculum dependent and was detectable within 4 h postinfection.The process was not completely reversible.Virus-specified uptake of IVAraU may allow automated in vitro detection of HSV isolates.
Bicyclic cytarabine analogues: Synthesis and investigation of antitumor properties of novel, 6-aryl- and 6-alkyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one arabinosides
Mieczkowski, Adam,Makowska, Malgorzata,Sekula, Justyna,Tomczyk, Ewelina,Zalewska, Ewa,Nasulewicz-Goldeman, Anna,Wietrzyk, Joanna
, p. 8454 - 8461 (2015)
A series of sixteen hitherto unknown Cytarabine analogues bearing a bicyclic 3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one base modified with aryl, pyridyl, benzyl and alkyl substituents was prepared in a straightforward approach. This is the one of the few exampl
Selective Acylation of Nucleosides, Nucleotides, and Glycerol-3-phosphocholine in Water
Fernández-García, Christian,Powner, Matthew W.
supporting information, p. 78 - 83 (2016/12/26)
A convenient selective synthesis of 2′,3′-di-O-acetyl-nucleotide-5′-phosphates, 2′,3′-di-O-acetyl-nucleotide-5′-triphosphates and 2′,3′,5′-tri-O-acetyl-nucleosides in water has been developed. Furthermore, a long-chain selective glycerol-3-phosphocholine diacylation is elucidated. These reactions are environmentally benign, rapid, high yielding, and the products are readily purified. Importantly, this reaction may indicate a prebiotically plausible reaction pathway for the selective acylation of key metabolites to facilitate their incorporation into protometabolism.
PROBE OF IODINE-123 MARKER THYMIDINE (FLT)ANALOGUE [123I]-IARAU
-
Paragraph 0020-0021, (2014/03/25)
A tumor radiation probe of iodine-123 marker thymidine (FLT) analogue [123I]-IaraU is disclosed. Commercial available uridine is used as the raw material for the synthesis of the precursor. A radioactive iodine-123 is marked on an alkaline group of uridine to obtain [123I]-IaraU, which is distinguishable from [18F]-FLT marking 18F on a glycosyl group to obtain a novel tumor radiation probe. The marking procedures include mixing the marker precursor with Na [123I] solution, acetic acid and hydrogen peroxide solution, and the solution of chloroform and sodium hydroxide. The sonication time increases from 1 minute to 10 minutes, so that [123I]-IaraU has radiologically chemical purity of higher than 98% and radiological specific activity of not less than 0.196 GBq/umole, and the yield can increase from 8% to 40%. Its radioactive specific activity, yield and purity reach to the degree for the use in biological experiments, while reducing production cost.
N4-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine - New drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate)
Schott, Herbert,Goltz, Daniel,Schott, Timm C.,Jauch, Claudia,Schwendener, Reto A.
scheme or table, p. 3520 - 3526 (2011/07/09)
Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N4-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleoside. The BPs moiety allows for a high binding to hydroxyapatite which is a prerequisite for bone targeting of the drugs. In vitro binding of 5-FdU-alendronate (5-FdU-ale) to hydroxyapatite showed a sixfold increased binding of these BPs as compared to 5-FdU. Exploratory cytotoxic properties of 5-FdU-ale were tested on a panel of human tumor cell lines resulting in growth inhibition ranging between 5% and 38%. The determination of IC 50-concentrations of the conjugate in Lewis lung carcinoma and murine macrophages showed an incubation time dependent growth inhibition with higher sensitivity towards the tumor cells. We assume that the antimetabolite-BPs can be cleaved into different active metabolites that may exert cytotoxic and other therapeutic effects. However, the underlying mechanisms of these promising new antimetabolite-BPs conjugates remain to be evaluated in future experiments.
A versatile synthesis of 5'-fenctionalized nucleosides through regioselective enzymatic hydrolysis of their peracetylated precursors
Bavaro, Teodora,Rocchietti, Silvia,Ubiali,Filice, Marco,Terreni, Marco,Pregnolato, Massimo
experimental part, p. 1967 - 1975 (2009/09/08)
We describe a chemo-enzymatic synthesis of modified nucleosides through lipase-catalyzed hydrolysis of their peracetylated precursors. It was found from screening of a large number of substrates that these enzymesregioselectivities were affected by the sugar and the nucleobase structures. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monodeprotecled purine and pyrimidine nucleosides useful as intermediates for the synthesis of high-value nucleosides and mononucleotides. By this approach, the chemo-enzymatic preparation of doxifluridine (14) and uridine 5'-monophosphate (5'-UMP, 15) from peracetylated uridine 1 was carried out. Elimination of many of the processing stages associated with existing methods was achieved, and higher yields and products of increased purity were generated. Wiley-VCH Verlag GmbH & Co. KGaA.
Growth inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium in vitro: Effect of 1-β-D-2′-arabinofuranosyl and 1-(2′-deoxy-2′-fluoro-β-D-2′-ribofuranosyl) pyrimidine nucleoside analogs
Johar, Monika,Manning, Tracey,Tse, Christopher,Desroches, Nancy,Agrawal,Kunimoto, Dennis Y.,Kumar, Rakesh
, p. 3696 - 3705 (2008/02/09)
The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-β-D-2′- arabinofuranosyl and 1-(2′-deoxy-2′-fluoro-β-D-rib
