Synthesis of Conformationally Constrained Nucleoside Analogues

Maougal, Esma; Escudier, Jean-Marc; Len, Christophe; Dubreuil, Didier; Lebreton, Jacques

doi:10.1002/9781118498088.ch9

Cited by 4 publications

(5 citation statements)

References 185 publications

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“…The presence of different kinds of bonds and substituents causes conformational flexibilities which relieve their different torsional strain and electronic strain. There are well-known examples available in the literature which confirms that the presence of fluoro substituent at a particular position in different therapeutically useful ligands fixes the conformation and alters or enhances the biological activities (Marquez et al 2004(Marquez et al , 1998Maougal et al 2013).…”

Section: Brief Outlook Of Fluoro Compoundsmentioning

confidence: 90%

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

et al. 2023

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During the last twenty years, organic fluorination chemistry established itself as an important tool to get a biologically active compound. This belief can be supported by the fact that every year, we are getting fluorinated drugs in the market in extremely significant numbers. Last year, also ten fluorinated drugs have been approved by FDA and during the COVID-19 pandemic, fluorinated drugs played a very crucial role to control the disease and saved many lives. In this review, we surveyed all ten fluorinated drugs approved by FDA in 2021 and all fluorinated drugs which were directly-indirectly used during the COVID-19 period, and emphasis has been given particularly to their synthesis, medicinal chemistry, and development process. Out of ten approved drugs, one drug pylarify, a radioactive diagnostic agent for cancer was approved for use in positron emission tomography imaging. Also, very briefly outlined the significance of fluorinated drugs through their physical, and chemical properties and their effect on drug development.

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Section: Brief Outlook Of Fluoro Compoundsmentioning

confidence: 90%

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

et al. 2023

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“…3′-O-acetyl-5′-O-tosyl-2′-deoxy-2′fluorouridine (12), when treated with 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) in boiling acetonitrile, was transformed into acetyl-protected 2′-deoxy-2′-fluoro-2,5′-O-cyclouridine nucleoside 13. Removal of acetyl-protected group with potassium carbonate, and treatment deprotected 2′-deoxy-2′-fluoro-2,5′-O-cyclouridine (14) with methanolic ammonia led to the isocytosine 2′-deoxy-2′-fluororiboside (15). Nucleoside 15, when treated with aqueous ammonia solution at elevated temperatures, underwent cyclisation leading to another type of cyclonucleoside, 2,2′-imino-1-(2-deoxy-β-D-arabinofuranosyl)uracil (16), possessing an imino group in the linkage connecting ribose and pyrimidine rings.…”

Section: The Synthesis Of Pyrimidine Cyclonucleosidesmentioning

confidence: 99%

“…The methods of synthesis of cyclonucleosides and their applications in medicinal chemistry were described in two review articles published by the corresponding author 12 years ago [13,14]. Some aspects of cyclonucleoside chemistry were also included in two consequent reviews published in 2012 [15] and 2013 year [16]. Since then, many new articles about cyclonucleosides have appeared, revealing new approaches to synthesis, as well as their new applications in organic synthesis and for the invention and development of biologically active substances.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and applications of cyclonucleosides: an update (2010–2023)

Burchiellaro,

Mieczkowski

2023

Mol Divers

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Cyclonucleosides are a group of nucleoside derivatives which, in addition to the classical N-glycosidic bond, have an additional covalent bond (linker, bridge) in their structure, which connects the heterocyclic base and sugar ring. The majority of them have been discovered in the laboratory; however, few such compounds have also been found in natural sources, including metabolites of sponges or radical damage occurring in nucleic acids. Due to their structural properties—rigid, fixed conformation—they have found wide applications in medicinal chemistry and biochemistry as biocides as well as enzyme inhibitors and molecular probes. They have also found use as convenient synthetic tools for the preparation of new nucleoside analogues, enabling structural modifications of both the sugar ring and heterocyclic base. This review summarizes the recent progress in the synthesis of various purine and pyrimidine cyclonucleosides using diverse chemical approaches based on radical, “click”, metal-mediated, and other types of reactions. It also presents recent reports concerning possible applications in medicinal chemistry, as well as their applications as valuable key intermediates in the synthesis of sugar- and base-modified nucleoside analogues and heterocyclic compounds. Graphical abstract

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“…There is an apparent effect of sugar conformational change on biological activity. [45] Kinase phosphorylation and polymerase-catalyzed incorporation step are highly dependent on the type of sugar conformation. South conformation of sugar is preferentially phosphorylated by kinase while on the other hand North type nucleoside is preferentially incorporated by polymerases.…”

Section: Conformational Biased Modified Nucleosidementioning

confidence: 99%

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

Pal

Chandra

Patel

et al. 2022

The Chemical Record

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Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.

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Synthesis of Conformationally Constrained Nucleoside Analogues

Cited by 4 publications

References 185 publications

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Synthesis and applications of cyclonucleosides: an update (2010–2023)

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

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