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Your search keyword '"Nuala M. Maguire"' showing total 2 results
Start Over Author "Nuala M. Maguire" Journal the journal of organic chemistry
2 results on '"Nuala M. Maguire"'

1. Synthesis of Guanine α-Carboxy Nucleoside Phosphonate (G-α-CNP), a Direct Inhibitor of Multiple Viral DNA Polymerases

Author

Alan Ford, Jan Balzarini, Nuala M. Maguire, and Anita R. Maguire

Subjects
Allylic rearrangement, Guanine, DNA polymerase, Stereochemistry, Organophosphonates, Chemistry Techniques, Synthetic, DNA-Directed DNA Polymerase, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Alpha-carboxy nucleoside phosphonate, Herpes virus, Cyclopentene, Polymerase, Nucleic Acid Synthesis Inhibitors, biology, 010405 organic chemistry, Organic Chemistry, Reverse transcriptases, HIV, Purine Nucleosides, Phosphonate, Polymerase active site, 0104 chemical sciences, 3. Good health, Enantiopure drug, chemistry, HIV-1, biology.protein, Nucleoside, Palladium
Abstract

The synthesis of guanine α-carboxy nucleoside phosphonate (G-α-CNP) is described. Two routes provide access to racemic G-α-CNP 9, one via base construction and the other utilizing Tsuji-Trost allylic substitution. The latter methodology was also applied to the enantiopure synthesis of both antipodes of G-α-CNP, each of which showing interesting antiviral DNA polymerase activity. Additionally, we report an improved multigram scale preparation of the cyclopentene building block 10, starting material for the preferred Tsuji-Trost route to 9.

Published
2018

2. Design and Synthesis of α-Carboxy Nucleoside Phosphonate Analogues and Evaluation as HIV-1 Reverse Transcriptase-Targeting Agents

Author

Alan Ford, Sarah Keane, Nicholas D. Mullins, Anita R. Maguire, Thibaut Legigan, Jan Balzarini, and Nuala M. Maguire

Subjects
Organophosphorus compounds, Models, Molecular, Anti-HIV Agents, Stereochemistry, Organophosphonates, Human immunodeficiency virus (HIV), Reaction products, medicine.disease_cause, Antiviral Agents, Catalysis, Structure-Activity Relationship, chemistry.chemical_compound, Organic compounds, medicine, Humans, Phosphorylation, Immunodeficiency-virus type-1, Inhibitors, Chemistry, Organic Chemistry, Nucleosides, Phosphonate, Reverse transcriptase, 3. Good health, Nucleic acids, Carbocyclic nucleoside, Drug Design, HIV-1, Nucleic acid, Reverse Transcriptase Inhibitors, Nucleoside, Palladium
Abstract

The synthesis of the first series of a new class of nucleoside phosphonate analogues is described. Addition of a carboxyl group at the α position of carbocyclic nucleoside phosphonate analogues leads to a novel class of potent HIV reverse transcriptase (RT) inhibitors, α-carboxy nucleoside phosphonates (α-CNPs). Key steps in the synthesis of the compounds are Rh-catalyzed O–H insertion and Pd-catalyzed allylation reactions. In cell-free assays, the final products are markedly inhibitory against HIV RT and do not require phosphorylation to exhibit anti-RT activity, which indicates that the α-carboxyphosphonate function is efficiently recognized by HIV RT as a triphosphate entity, an unprecedented property of nucleoside monophosph(on)ates.

Published
2015

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