Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors

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dc.contributor.advisorHunter, Rogeren_ZA
dc.contributor.authorMuhanji, Clare Imbosaen_ZA
dc.date.accessioned2014-08-13T14:27:31Z
dc.date.available2014-08-13T14:27:31Z
dc.date.issued2006en_ZA
dc.descriptionIncludes bibliographical references (leaves 182-190).en_ZA
dc.description.abstractThis thesis describes the design and synthesis of bifunctional drugs combining anucleoside (d4U) and non-nucleoside (HI-236) reverse transcriptase inhibitor linkedvia different spacers between C-5 of the NRTI and 0-1 of the NNRTI. Three targets were successfully synthesized in a divergent manner from uridine in 13steps for the butyne target and 19 steps for targets bearing PEG-propyne units usingSonogashira coupling as a key step. The most challenging step of the synthesisinvolved Boc deprotection and thiourea condensation in the final step, which sufferedfrom anomeric cleavage with loss of the sugar moiety. As a result, the target with athree-carbon propynyl spacer could not be accessed. Progress towards the synthesis of a bifunctional system bearing a saturated andmore flexible tether is highlighted in Chapter 4. The key reactions includedSonogashira coupling of iodo nucleosides, 2',3'-dideoxygenation of the vicinol diol,phenolic alkylation and condensation of amine with thiourea reagent. The synthesissurmounted several challenges, with chemoselective distinction of unsaturation vialate introduction of the d4U double bond using Corey-Winter methodology as thehighlight.en_ZA
dc.identifier.apacitationMuhanji, C. I. (2006). <i>Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6346en_ZA
dc.identifier.chicagocitationMuhanji, Clare Imbosa. <i>"Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006. http://hdl.handle.net/11427/6346en_ZA
dc.identifier.citationMuhanji, C. 2006. Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Muhanji, Clare Imbosa AB - This thesis describes the design and synthesis of bifunctional drugs combining anucleoside (d4U) and non-nucleoside (HI-236) reverse transcriptase inhibitor linkedvia different spacers between C-5 of the NRTI and 0-1 of the NNRTI. Three targets were successfully synthesized in a divergent manner from uridine in 13steps for the butyne target and 19 steps for targets bearing PEG-propyne units usingSonogashira coupling as a key step. The most challenging step of the synthesisinvolved Boc deprotection and thiourea condensation in the final step, which sufferedfrom anomeric cleavage with loss of the sugar moiety. As a result, the target with athree-carbon propynyl spacer could not be accessed. Progress towards the synthesis of a bifunctional system bearing a saturated andmore flexible tether is highlighted in Chapter 4. The key reactions includedSonogashira coupling of iodo nucleosides, 2',3'-dideoxygenation of the vicinol diol,phenolic alkylation and condensation of amine with thiourea reagent. The synthesissurmounted several challenges, with chemoselective distinction of unsaturation vialate introduction of the d4U double bond using Corey-Winter methodology as thehighlight. DA - 2006 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors TI - Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors UR - http://hdl.handle.net/11427/6346 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6346
dc.identifier.vancouvercitationMuhanji CI. Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6346en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleSynthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitorsen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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