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Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids
Includes bibliographical references.
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Department of Chemistry
2016
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| _version_ | 1867613301405384704 |
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| access_status_str | Open Access |
| author | Mountford, Pia Gail |
| author2 | Bull, James R |
| author_browse | Bull, James R Mountford, Pia Gail |
| author_facet | Bull, James R Mountford, Pia Gail |
| author_sort | Mountford, Pia Gail |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/17901 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:57.504Z |
| 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:11427/17901 Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids Mountford, Pia Gail Bull, James R Chemistry Includes bibliographical references. An efficient synthetic strategy for the stereoselective introduction of a 14β-allyl group to estrone 3-methyl ether has been developed. The approach involves regio- and stereoselective Diets-Alder cycloaddition of acrolein to 3-methoxyestra-1,3,5(10),14,16- pentaen-17-yl acetate. Hydride reduction of the formyl group of the cycloadduct, followed by tosylation of the resultant primary hydroxy group, gave rise to a 17β-alkoxy 16¹-tosylate. Base-mediated Wharton fragmentation of the 1,3-removed diol derivative produced the 14β-allyl Δ¹⁵-17-ketone. Chemoselective conjugate reduction of the ring enone gave rise to 14-allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one in 51% overall yield for five steps. Regioselective oxidation of the 14β-allyl group furnished precursors for intramolecular coupling reactions with the 17-oxo group, providing access to a series of 14β,17β-propanoestradiol and 'estriol' analogues. Wacker oxidation of the 14-allyl-3-methoxy-14β-estra-1,3,5(10),15-tetraen-17- one gave rise to both the 14β-acetonyl and 14β-formylethyl derivatives. The acetonyl enone underwent cerium(III)-mediated aldol condensation with the 17-oxo group to yield the 14β,17β-propano Δ¹⁵-estradiol analogue. This series of β-face propano bridged estradiols displayed no competitive binding affinity for the estradiol receptor. The enolisable 14β-acetonyl group was also shown to undergo smooth Michael addition to C(15). The product, 3-methoxy-3'H,l5αH-cyclopenta[14,15]-14β-estra-1,3,5(10)-triene- 4'(5'H),17-dione, was regioselectively deoxygenated and reduced to yield the 3,17- estradiol analogues. The 3,17β-estradiol displayed promising binding affinity for the estradiol receptor site, whereas the 17α-epimer was biologically inactive. The 14β-formylethyl enone underwent vinylogous reductive cyclisation with C(lS), to yield the 3'-hydroxy cyclopenta[14,15] 17-ketone. No regioselective coupling with the 17-oxo group was observed. Various attempts to homologate ring D of the 14β-allyl 17-ketone or its Δ¹⁵-analogue are described, none of which were successful. However, the silyl enol ether derivative of estrone 3-methyl ether underwent facile cyclopropanation of the Δ¹⁶-bond. Iron(III) chloride-mediated cleavage of the zero bridge of the resultant bicyclo[3.1.0] hexanoid intermediate gave rise to the D-homo Δ¹⁶-17a-ketone. Conversion of the en one into the derived 14,16-dienyl 17a-ketone furnished an intermediate for conjugate addition studies. 2016-03-17T07:18:47Z 2016-03-17T07:18:47Z 1995 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/17901 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Chemistry Mountford, Pia Gail Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| thesis_degree_str | Doctoral |
| title | Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| title_full | Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| title_fullStr | Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| title_full_unstemmed | Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| title_short | Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids |
| title_sort | novel synthetic routes to 14β 17β propano and cyclopenta 14 15 19 norsteroids |
| topic | Chemistry |
| url | http://hdl.handle.net/11427/17901 |
| work_keys_str_mv | AT mountfordpiagail novelsyntheticroutesto14b17bpropanoandcyclopenta141519norsteroids |