Novel acyclic nucleotide phosphonates against RNA viruses

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.

Grantor dc:publisher.institution

Department of Chemistry

Year dc:date.issued

2012

Author dc:creator

• Bowden, Gregory David

Advisor dc:contributor.advisor

• Hunter, Roger

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/10258

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/10258