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Synthesis and structure activity relationships of ring D modified steroidal hormones
Includes bibliographical references.
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Chemistry
2016
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| _version_ | 1867613335399170048 |
|---|---|
| access_status_str | Open Access |
| author | Jardine, Mogamad Anwar |
| author2 | Bull, James R |
| author_browse | Bull, James R Jardine, Mogamad Anwar |
| author_facet | Bull, James R Jardine, Mogamad Anwar |
| author_sort | Jardine, Mogamad Anwar |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/17900 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:34:28.941Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| 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:11427/17900 Synthesis and structure activity relationships of ring D modified steroidal hormones Jardine, Mogamad Anwar Bull, James R Chemistry Includes bibliographical references. The synthesis of steroidal 14α,16-methano, 14α,17-methano-, 14α,17-ethano- and 14α,17-propano estradiol analogues as well as 14α-alkyl and 14α-functionalised-alkyl estradiol analogues was investigated. Furthermore, the synthesis of 17β-hydroxy-17α, 14-(epoxymethano)androst-4-en-3-one was undertaken and acid-mediated rearrangement of the 14,17-etheno bridged testosterone analogue gave the 14,16-ethano analogue of androst-4-en-3,17-dione. Established ring D cycloaddition and oxidative cleavage methodology gave ring D 14α-formyl and 14α, 17α-diformyl compounds as key intermediates in the overall synthetic plan. Chemoselective- and stereoselective nucleophilic addition at C-14¹ of the 14α-formyl-3-methoxyestra-1,3,5(10)-trien-17-one provided access to 14α-alkyl- and 14α-alkyl-functionalised 19-norsteroids for elaboration toward 14α,17-propano- and 14α-alkylamide estradiol analogues. Synthesis of the 14α,17-methano bridged steroid was attainable indirectly through intramolecular pinacol coupling between the 17-oxo- and 14-formyl group of 14αformyl- 3-methoxyestra-1,3,5(10)-trien-17-one. The 14α, 16-methano bridged steroid was synthesised via base-mediated intramolecular cyclisation of 14-(toluene-p-sulfonyloxy)methyl-3-methoxyestra-1,3,5( 1 0)-trien-17-one. Novel compounds were characterised with the aid of high field NMR techniques. A X-ray crystal structure determination of the strained ring D 14α, 17-methano bridged estriol analogue corroborated its structure. The minimum energy conformation of novel estradiol analogues were superimposed on estradiol, and their least square fit values determined and discussed in relation to biological activity. These analogues will contribute toward defining the structural parameters responsible for certain pattern of hormonal activity, and hence, the ultimate goal of predictive drug design. 2016-03-17T07:18:45Z 2016-03-17T07:18:45Z 1995 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/17900 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Chemistry Jardine, Mogamad Anwar Synthesis and structure activity relationships of ring D modified steroidal hormones |
| thesis_degree_str | Doctoral |
| title | Synthesis and structure activity relationships of ring D modified steroidal hormones |
| title_full | Synthesis and structure activity relationships of ring D modified steroidal hormones |
| title_fullStr | Synthesis and structure activity relationships of ring D modified steroidal hormones |
| title_full_unstemmed | Synthesis and structure activity relationships of ring D modified steroidal hormones |
| title_short | Synthesis and structure activity relationships of ring D modified steroidal hormones |
| title_sort | synthesis and structure activity relationships of ring d modified steroidal hormones |
| topic | Chemistry |
| url | http://hdl.handle.net/11427/17900 |
| work_keys_str_mv | AT jardinemogamadanwar synthesisandstructureactivityrelationshipsofringdmodifiedsteroidalhormones |