- Synthesis of imidazole-activated ribonucleotides using cyanogen chloride
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We report the syntheses of ribonucleoside 5′-monophosphates activated with imidazole, using a mechanism which relies on the in situ generation of cyanogen chloride from the reaction of cyanide anion with hypochlorous acid. Cyanogen chloride reacts rapidly with imidazole to form diimidazole imine as the major product, a species which affords the activation of ribonucleoside 5′-monophosphates to their 5′-phosphorimidazolides.
- Yi, Ruiqin,Hongo, Yayoi,Fahrenbach, Albert C.
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supporting information
p. 511 - 514
(2018/01/19)
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- A Simple synthesis of sugar nucleoside diphosphates by chemical coupling in water
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Sugar nucleotides made easy: The new reagent ImIm , which is formed in-situ in water, is shown to activate nucleoside 5'-phosphates to their imidazolides, these can subsequently couple with sugar-1-phosphates; the whole procedure takes place in water. This truly simple method yields a crude product mixture that can be used directly as a source of donors for glycosyltransferase- mediated oligsaccharide synthesis. In the scheme, B stands for the nucleobases U, A, or G. Copyright
- Tanaka, Hidenori,Yoshimura, Yayoi,Jürgensen, Malene R.,Cuesta-Seijo, Jose A.,Hindsgaul, Ole
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supporting information
p. 11531 - 11534
(2013/01/15)
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- Synthesis of nucleoside phosphosulfates
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We describe an efficient and scalable procedure for the chemical synthesis of nucleoside 5′-phosphosulfates (NPS) from nucleoside 5′-phosphorimidazolides and sulfate bis(tributylammonium) salt. Using this method we obtained various NPS with yields ranging from 70-90%, including adenosine 5′-phosphosulfate (APS) and 2′,3′-cyclic precursor of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), which are the key intermediates in the assimilation and metabolism of sulfur in all living organisms.
- Kowalska, Joanna,Osowniak, Agnieszka,Zuberek, Joanna,Jemielity, Jacek
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p. 3661 - 3664
(2012/07/27)
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- Convenient synthesis of nucleoside-5′-diphosphates from the corresponding ribonucleoside-5′-phosphoroimidazole
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The reaction of ribonucleoside-5′-phosphoroimidazolide with a tributylammonium orthophosphate in anhydrous dimethylformamide at room temperature provides a general method for the synthesis of nucleoside-5′- diphosphate. The novelty of the approach is to use the triethylammonium salt of 5′-monophosphate nucleoside derivative prior to the imidazolate reaction with imidazole, triphenylphosphine, and 2,2′-dithiodipyridine. Deprotection, followed by displacement of the imidazole moiety using tributylammonium orthophosphate and a catalytic amount of zinc chloride in dimethylformamide gave the desired 5′-diphosphate products. The triethyl ammonium salt of 5′-diphosphate nucleosides was purified by flash chromatography using DEAE (diethylaminoethyl weak anion exchange resin) Sepharosa fast flow packed in an XK 50/60 column on an Akta FPLC (Fast Protein Liquid Chromatography). Synthesis procedures are reported for adenosine-5′-diphosphate, uridine-5′-diphosphate, cytidine-5′-diphosphate, and guanosine-5′-diphosphate. Yields for the displacement reactions ranged from 95 to 97%. Thus, this method offers the advantages of shorter reaction time, greater product yield, and a more cost-effective synthetic route. Copyright Taylor & Francis Group, LLC.
- Kore, Anilkumar R.,Parmar, Gaurang
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p. 3393 - 3399
(2007/10/03)
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- Engineering human FHIT, a diadenosine triphosphate hydrolase, into an efficient dinucleoside polyphosphate synthase
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The putative human tumor suppressor gene FHIT encodes Fhit, the fragile histidine triad protein. Fhit is thought to participate in a signal transduction pathway involving dinucleoside polyphosphates. Fhit catalyzes the Mg2+-dependent hydrolysis of P1-5′-O-adenosine-P3-5′-O-adenosine triphosphate (Ap3A) to AMP and MgADP. Mutation of His96 to glycine disables Fhit as a catalyst for the hydrolysis of phosphoanhydrides such as Ap3A. However, the mutated enzyme H96G-Fhit efficiently catalyzes the synthesis of phosphoanhydride bonds in reactions of nucleoside-5′-phosphimidazolides with nucleoside di- and triphosphates. H96G-Fhit can be employed in the synthesis of a wide range of dinucleoside tri- and tetraphosphates. We here describe the use of H96G-Fhit to catalyze the synthesis of Ap3A, Ap3C, Ap3G, Ap3T, Ap3U, Cp3U, Tp3U, dAp3U, Ap4A, Ap4U, and the fluorescent Ap4etheno-C. Copyright
- Huang, Kaisheng,Frey, Perry A.
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p. 9548 - 9549
(2007/10/03)
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- Efficient One-Step Syntheses of Isoprenoid Conjugates of Nucleoside 5′-Diphosphates
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(Equation presented) Isoprenoid conjugates of nucteoside 5′-diphosphates were efficiently synthesized by one-step nucleophilic displacement reactions of either isoprenyl chlorides or isopentenyl tosylate with nucleoside 5′-diphosphates.
- Ryu, Youngha,Scott, A. Ian
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p. 4713 - 4715
(2007/10/03)
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- Potent inhibitors of human inosine monophosphate dehydrogenase type II. Fluorine-substituted analogues of thiazole-4-carboxamide adenine dinucleotide
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Three analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) (1- 3) containing a fluorine atom at the C2' of the adenine nucleoside (in the ribo and arabino configuration) and at the C3' (in the ribo configuration) were synthesized in high yield from the corresponding 5'-monophosphates of 2'-deoxy-2'-fluoroadenosine (9), 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)- adenine (17), and 3'-deoxy-3'-fluoroadenosine (14), respectively. Pure 2',3'- O-isopropylidene-tiazofurin 5'-phosphorimidazolide (8) was obtained by phosphorylation of the protected tiazofurin followed by treatment with carbonyldiimidazole and HPLC purification. Reaction of 8 with 9 in DMF-d7 (monitored by 1H and 31P NMR) afforded the desired dinucleotide 12, which after deisopropylidenation gave 1 in 82% yield. Small amounts of symmetrical dinucleotides AppA (10, 7.2%) and TRppTR (11, 8.0%) were also isolated during HPLC purification of the major product 12. In a similar manner, compounds 2 and 3 were obtained by coupling of 8 with 14 and 17 in 80% and 76% yield, respectively. All newly prepared fluoro-substituted compounds as well as β- CF2-TAD, earlier synthesized by us, showed good inhibitory activity against inosine monophosphate dehydrogenase type II, the isozyme which is predominant in neoplastic cells. Binding of 1 (K(is) = 0.5 μM), 2 (K(is) = 0.7 μM), and 3 (K(is) = 2.9 μM) was comparable to that of TAD (K(i) = 0.2 μM). The difluoromethylene bisphosphonate analogue, β-CF2-TAD (K(i) = 0.17 μM), was found to be equally effective as the best cofactor-type inhibitor, β-CH2- TAD (K(i) = 0.11 μM). Interestingly, the level of inhibition of horse liver alcohol dehydrogenase by these compounds was found to be much lower (0.1 mM for 1 and 2 and no inhibition up to 10 mM for 3). These findings show that inhibition of tumor-induced inosine monophosphate dehydrogenase type II is selective and may be of therapeutic interest.
- Zatorski,Goldstein,Colby,Jones,Pankiewicz
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p. 1098 - 1105
(2007/10/02)
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- Convenient syntheses of cytidine 5'-triphosphate, guanosine 5'-triphosphate, and uridine 5'-triphosphate and their use in the preparation of UDP-glucose, UDP-glucuronic acid, and GDP-mannose
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This paper compares enzymatic and chemical methods for the synthesis of cytidine 5'-triphosphate, guanosine 5'-triphosphate, and uridine 5'-triphosphate from the corresponding nucleoside monophosphates on scales of ~10 g. These nucleoside triphosphates are important as intermediates in Leloir pathway biosyntheses of complex carbohydrates; the nucleoside monophosphates are readily available commercially. The best route to CTP is based on phosphorylation of CMP using adenylate kinase (EC 2.7.4.3); the route to GTP involves phosphorylation of GMP using guanylate kinase (EC 2.7.4.8); chemical deamination of CTP (prepared enzymatically from CMP) is the best synthesis of UTP. For the 10-200-mmol-scale reactions described in this paper, it is more convenient to prepare phosphoenolpyruvate (PEP), used in the enzymatic preparations, from D-(-)-3-phosphoglyceric acid (3-PGA) in the reaction mixture rather than to synthesize PEP in a separate chemical step. The in situ conversion of 3-PGA to PEP requires the coupled action of phosphoglycerate mutase (EC 2.7.5.3) and enolase (EC 4.2.1.11). The enzyme-catalyzed syntheses of uridine 5'-diphosphoglucose (UDP-Glc), uridine 5'-diphosphoglucuronic acid (UDP-GlcUA), and guanosine 5'-diphosphomannose (GDP-Man) illustrate the use of the nucleoside triphosphates.
- Simon,Grabowski,Whitesides
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p. 1834 - 1841
(2007/10/02)
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