957-75-5Relevant articles and documents
Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies
Ximenes, Valdecir Farias,Morgon, Nelson Henrique,De Souza, Aguinaldo Robinson
, p. 61 - 68 (2015)
Abstract Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br-). The blood plasma level of Br- is more than 1,000-fold lower than that of chloride anion (Cl-). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2 = 2.3 × 102 M- 1 s- 1, HOCl non-reactive); dansylglycine (HOBr, k2 = 7.3 × 106 M- 1 s- 1, HOCl, 5.2 × 102 M- 1 s- 1); salicylic acid (HOBr, k2 = 4.0 × 104 M- 1 s- 1, non-reactive); 3-hydroxybenzoic acid (HOBr, k2 = 5.9 × 104 M- 1 s- 1, HOCl, k2 = 1.1 × 101 M- 1 s- 1); uridine (HOBr, k2 = 1.3 × 103 M- 1 s- 1, HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile.
The synthesis and antituberculosis activity of 5-alkynyl uracil derivatives
Platonova, Yana B.,Tomilova, Larisa G.,Volov, Alexander N.
, (2020/06/26)
A series of new 5-alkynyl-substituted uracil and uridine derivatives were synthesised via palladium-catalysed Sonogashira cross-coupling reaction of 5-bromo-pyrimidine base with terminal acetylenes with good yields in DMF at room temperature. All obtained compounds were tested for antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis (H37Ra) at concentrations of 1–100 μg/ml using MABA test. Obtained results revealed that most of tested uracil derivatives exhibited high antimycobacterial activity (MIC50 = 1.1–19.2 μg/ml) in comparison with therapeutic agents such as rifampicin, isoniazid and D-cycloserine, excluding compounds having alkyl substituent at triple alkyne bond.
Use of nucleoside phosphorylases for the preparation of 5-modified pyrimidine ribonucleosides
Alexeev, Cyril S.,Drenichev, Mikhail S.,Dorinova, Evgeniya O.,Esipov, Roman S.,Kulikova, Irina V.,Mikhailov, Sergey N.
, (2019/11/13)
Enzymatic transglycosylation, a transfer of the carbohydrate moiety from one heterocyclic base to another, is catalyzed by nucleoside phosphorylases (NPs) and is being actively developed and applied for the synthesis of biologically important nucleosides. Here, we report an efficient one-step synthesis of 5-substitited pyrimidine ribonucleosides starting from 7-methylguanosine hydroiodide in the presence of nucleoside phosphorylases (NPs).
Thermodynamic Reaction Control of Nucleoside Phosphorolysis
Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
supporting information, p. 867 - 876 (2020/01/24)
Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).
SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS
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, (2019/01/15)
This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.
ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF
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Page/Page column 621, (2016/06/15)
The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF
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Page/Page column 629, (2016/06/28)
The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
Alternative nucleic acid molecules and uses thereof
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Paragraph 2169; 2170, (2015/11/09)
The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them.
Direct One-Pot Synthesis of Nucleosides from Unprotected or 5-O-Monoprotected d -Ribose
Downey, A. Michael,Richter, Celin,Pohl, Radek,Mahrwald, Rainer,Hocek, Michal
, p. 4604 - 4607 (2015/09/28)
New, improved methods to access nucleosides are of general interest not only to organic chemists but to the greater scientific community as a whole due their key implications in life and disease. Current synthetic methods involve multistep procedures employing protected sugars in the glycosylation of nucleobases. Using modified Mitsunobu conditions, we report on the first direct glycosylation of purine and pyrimidine nucleobases with unprotected d-ribose to provide β-pyranosyl nucleosides and a one-pot strategy to yield β-furanosides from the heterocycle and 5-O-monoprotected d-ribose.
MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF
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Page/Page column 288; 289, (2014/07/07)
The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.
