Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors
Includes bibliographical references (leaves 182-190).
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Chemistry
2014
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613208694489088 |
|---|---|
| access_status_str | Open Access |
| author | Muhanji, Clare Imbosa |
| author2 | Hunter, Roger |
| author_browse | Hunter, Roger Muhanji, Clare Imbosa |
| author_facet | Hunter, Roger Muhanji, Clare Imbosa |
| author_sort | Muhanji, Clare Imbosa |
| collection | Thesis |
| description | Includes bibliographical references (leaves 182-190). |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/6346 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:29.432Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/6346 Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors Muhanji, Clare Imbosa Hunter, Roger Chemistry Includes bibliographical references (leaves 182-190). 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. 2014-08-13T14:27:31Z 2014-08-13T14:27:31Z 2006 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/6346 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Chemistry Muhanji, Clare Imbosa Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| thesis_degree_str | Doctoral |
| title | Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| title_full | Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| title_fullStr | Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| title_full_unstemmed | Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| title_short | Synthesis and anti-HIV activity of [d4U]-spacer-[HI-236] bifinctional HIV-1 reverse transcriptase inhibitors |
| title_sort | synthesis and anti hiv activity of d4u spacer hi 236 bifinctional hiv 1 reverse transcriptase inhibitors |
| topic | Chemistry |
| url | http://hdl.handle.net/11427/6346 |
| work_keys_str_mv | AT muhanjiclareimbosa synthesisandantihivactivityofd4uspacerhi236bifinctionalhiv1reversetranscriptaseinhibitors |