{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/17901"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/17901","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Mountford, Pia Gail"],"institution":"Department of Chemistry","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bull, James R"],"committee_chairs":[],"committee_members":[],"year":1995,"date_issued":"1995","date_published":"1995","updated_at":"2026-07-22T22:23:19Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/17901","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bull, James R"]},{"key":"dc:creator","label":"Author","values":["Mountford, Pia Gail"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-03-17T07:18:47Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-03-17T07:18:47Z"]},{"key":"dc:date.issued","label":"Date","values":["1995"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cape Town"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/17901"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Includes bibliographical references."]},{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bull, James R"],"dc:creator":["Mountford, Pia Gail"],"dc:date.accessioned":["2016-03-17T07:18:47Z"],"dc:date.available":["2016-03-17T07:18:47Z"],"dc:date.issued":["1995"],"dc:description":["Includes bibliographical references."],"dc:description.abstract":["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."],"dc:identifier.uri":["http://hdl.handle.net/11427/17901"],"dc:language.iso":["eng"],"dc:publisher.department":["Department of Chemistry"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["Novel synthetic routes to 14β,17β-Propano and cyclopenta [14,15]19-norsteroids"],"dc:type":["Doctoral Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-22T22:23:19Z"}