Synthesis of phosphorus/sulfur-based antivirals

Simple item page
dc.check.chapterOfThesisN/Aen
dc.check.date9999-12-31
dc.contributor.advisorO'Sullivan, Tim
dc.contributor.authorCollins, Emily Agnesen
dc.contributor.funderResearch Irelanden
dc.date.accessioned2026-05-28T09:11:15Z
dc.date.available2026-05-28T09:11:15Z
dc.date.issued2025-08-12
dc.date.submitted2025-08-12
dc.description.abstractThe Human Immunodeficiency Virus is a major global health problem. Although a number of effective combination therapies are available, drug resistance remains an ongoing concern due to the rapid mutation rate of the virus. Novel antivirals are continually required to combat evolving resistance. By making structural modifications to existing antiviral agents, the rate of antiviral incorporation into the viral DNA chain may be accelerated leading to more rapid termination of viral replication. Chapter 1 discusses the strategy of bioisosteric replacement and the rationale for choosing the phosphonodithioate functional group as a suitable bioisostere. An in-depth review of the conversion of alkyl halides to alcohols is also outlined in this chapter. The preparation of the antiviral agent adefovir is detailed in Chapter 2. The derivatisation of adefovir via the corresponding phosphonic dichloride intermediate and under Garegg-Samuelsson reaction conditions is further discussed. The preparation of novel butyl and dibutyl phosphonate analogues of adefovir using both approaches is described. Attempted coupling of the corresponding sulfur-based analogues is also outlined in this chapter. A synthetic route to two novel phosphonodithioate-containing alcohols is detailed in Chapter 3. Installation of the key carbon-nitrogen bond under Mitsunobu conditions is explored with this strategy ultimately proving unsuccessful. Chapter 4 outlines the preparation of aryl-linked phosphonates and phosphonic acids via copper-catalysed Chan-Lam coupling of adenine-derived nucleobases with boronic acids and esters. Ten novel aryl-linked phosphonates/phosphonic acids were successfully synthesised and have been evaluated for activity against HIV and hepatitis B. The application of this synthetic strategy to phosphonodithioate-containing compounds is also discussed. Computational analysis of our novel aryl-linked analogues is described in Chapter 5. The physicochemical properties of each compound are evaluated against Lipinski’s Rules and Veber’s Rules while the compounds have also been screened for PAINS alerts and organ-specific toxicities. 3D analysis of these compounds is also presented. Chapter 6 details our main conclusions and future work on this project while full experimental procedures, including spectroscopic and analytical data, is outlined in Chapter 7.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCollins, E. A. 2025. Synthesis of phosphorus/sulfur-based antivirals. PhD Thesis, University College Cork.
dc.identifier.endpage303
dc.identifier.urihttps://hdl.handle.net/10468/18922
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectResearch Ireland (Grant no. GOIPG/2021/264)
dc.rights© 2025, Emily Agnes Collins.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectHIVen
dc.subjectAIDSen
dc.subjectDNAen
dc.subjectRNAen
dc.subjectRetrovirusen
dc.subjectAntiviralen
dc.subjectNRTIen
dc.subjectAcyclicen
dc.subjectAdefoviren
dc.subjectOxygenen
dc.subjectSulfuren
dc.subjectPhosphorusen
dc.subjectGaregg-Samuelssonen
dc.subjectMitsunobuen
dc.subjectChan-Lamen
dc.subjectBiologicalen
dc.subjectEvaluationen
dc.subjectComputationalen
dc.subjectNucleosideen
dc.subjectPhosphonateen
dc.subjectSATEen
dc.subjectPOMen
dc.subjectMicrowaveen
dc.subjectFinkelsteinen
dc.subjectArbuzoven
dc.subjectBorylationen
dc.subjectHepatitisen
dc.subjectPhosphonodithioateen
dc.subjectPhosphonothioateen
dc.titleSynthesis of phosphorus/sulfur-based antiviralsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
CollinsEA_PhD2025.pdf
Size:
9.3 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Theses
Analytical & Biological Chemistry Research Facility - Doctoral Theses
Chemistry - Doctoral Theses
College of Science, Engineering and Food Science - Doctoral Theses