Novel acyclic nucleotide phosphonates against RNA viruses

Bowden, Gregory David

Novel acyclic nucleotide phosphonates against RNA viruses

Master Thesis

2012

Publisher

University of Cape Town

Department

Department of Chemistry

Faculty

Faculty of Science

Abstract

Acyclic nucleotide phosphonates (ANPs) have been used for years as successful anti-viral agents against diseases such as HIV/AIDS and hepatitis while the drug ribavirin is one of the only drugs available for the treatment of RNA-viral infections which mainly affect the developing world. The large and unmet need for anti-RNA viral treatments has prompted this study into the design and synthesis of a range of ANPs, which includes a series of ribavirin-based ANP derivatives. The series of compounds was synthesised from a diisopropyl protected phosphonomethoxyethyl (PME) synthon and included an arylethynyltriazole derivative which was produced via a Sonogashira palladium catalysed cross-coupling reaction. A selection of these compounds was then deprotected to their corresponding phosphonic acids via a bromotrimethylsilane mediated phosphonate ester hydrolysis. In one example, a bis(pivaloyloxymethyl) prodrug variant was produced in order to probe a general synthesis for prodrug protected ANP derivatives. All new compounds were characterised by NMR, IR, and Mass spectroscopic techniques.

Description

Includes bibliographical references.

Keywords

Chemistry

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