{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/40005"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/40005","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Design and synthesis of rotational analogues of estradiol","abstract":"Studies have been conducted in synthesising bridged analogues of estradiol in which the ring D hydroxy group is displaced from the 17-position. The aim was to explore the possible rotational equivalence between such analogues and estr~diol. The synthetic routes investigated were based upon cycloaddition to 3-methoxyestra1,3,5(10), 14, 16-pentaene. In the first phase of the project, two approaches for the synthesis of this diene were explored. The first entailed the vinylogous Shapiro elimination of the tosylhydrazone of 3-methoxyestra-1,3,5(10),15-tetraen-17-one to give the 14,16-diene. The second involved conversion of 3-methoxyestra1,3,5(10), 15-tetraen-17-one into the corresponding dienyl triflate, followed by palladium(0) mediated deoxygenation to afford the 14, 16-diene. Of these two methods, only the latter was successful, as the tosylhydrazone of 3-methoxyestra1,3,5(10), 15-tetraen-17-one could not be synthesised. In the second phase of the work~ cycloaddition of 2-chloroacrylonitrile to the 14,16- diene, followed by alkaline hydrolysis afforded 3-methoxy-14, 17a.-ethenoestra- , 1,3,5(10)-trien-15-one and 3-methoxy-14, l 7a.-ethenoestra-l ,3,5(1 0)-trien-16-one, with the 15-ketone as the major isomer. Treatment of these ketones with LSelectride® afforded 3-methoxy-14, 17a.-ethenoestra-l ,3,5(10)-trien-15P-ol and 3- methoxy-14, 17 a.-ethenoestra-1,3 ,5(1 0)-trien-16P-oL Standard deprotection afforded the corresponding diols which were submitted for biological evaluation. An approach towards the corresponding a-alcohols which was investigated is based upon the Baeyer-Villiger oxidation of 16a.-acetyl-3-methoxy-l 4, 17a.-ethenoestra1,3,5(10)-triene. This compound was obtained as the minor product of the boron trifluoride mediated reaction between the 14, 16-diene and methyl vinyl ketone (MVK). The major compound was formulated 16a.-acetyl-3-methoxy-17P-3'- oxobutyl-14, l 7a.-ethenoestra-1,3,5(10)-triene, on the basis of the available spectral data. Reaction of MVK and the 14,16-diene under thermal conditions afforded the desired 16a.-acetyl compound as the major product. Attempts to perform the peracid mediated insertion ofoxygen were unsuccessful. The final phase of the work w","abstract_html":"Studies have been conducted in synthesising bridged analogues of estradiol in which the ring D hydroxy group is displaced from the 17-position. The aim was to explore the possible rotational equivalence between such analogues and estr~diol. The synthetic routes investigated were based upon cycloaddition to 3-methoxyestra1,3,5(10), 14, 16-pentaene. In the first phase of the project, two approaches for the synthesis of this diene were explored. The first entailed the vinylogous Shapiro elimination of the tosylhydrazone of 3-methoxyestra-1,3,5(10),15-tetraen-17-one to give the 14,16-diene. The second involved conversion of 3-methoxyestra1,3,5(10), 15-tetraen-17-one into the corresponding dienyl triflate, followed by palladium(0) mediated deoxygenation to afford the 14, 16-diene. Of these two methods, only the latter was successful, as the tosylhydrazone of 3-methoxyestra1,3,5(10), 15-tetraen-17-one could not be synthesised. In the second phase of the work~ cycloaddition of 2-chloroacrylonitrile to the 14,16- diene, followed by alkaline hydrolysis afforded 3-methoxy-14, 17a.-ethenoestra- , 1,3,5(10)-trien-15-one and 3-methoxy-14, l 7a.-ethenoestra-l ,3,5(1 0)-trien-16-one, with the 15-ketone as the major isomer. Treatment of these ketones with LSelectride® afforded 3-methoxy-14, 17a.-ethenoestra-l ,3,5(10)-trien-15P-ol and 3- methoxy-14, 17 a.-ethenoestra-1,3 ,5(1 0)-trien-16P-oL Standard deprotection afforded the corresponding diols which were submitted for biological evaluation. An approach towards the corresponding a-alcohols which was investigated is based upon the Baeyer-Villiger oxidation of 16a.-acetyl-3-methoxy-l 4, 17a.-ethenoestra1,3,5(10)-triene. This compound was obtained as the minor product of the boron trifluoride mediated reaction between the 14, 16-diene and methyl vinyl ketone (MVK). The major compound was formulated 16a.-acetyl-3-methoxy-17P-3'- oxobutyl-14, l 7a.-ethenoestra-1,3,5(10)-triene, on the basis of the available spectral data. Reaction of MVK and the 14,16-diene under thermal conditions afforded the desired 16a.-acetyl compound as the major product. Attempts to perform the peracid mediated insertion ofoxygen were unsuccessful. The final phase of the work w","abstract_has_math":false,"creators":["Seymour, Anthony James"],"institution":"Department of Chemistry","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bull, J.R"],"committee_chairs":[],"committee_members":[],"year":1999,"date_issued":"1999","date_published":"1999","updated_at":"2026-07-22T22:22:39Z","subjects":["Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/40005","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bull, J.R"]},{"key":"dc:creator","label":"Author","values":["Seymour, Anthony James"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-06-20T12:51:18Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-06-20T12:51:18Z"]},{"key":"dc:date.issued","label":"Date","values":["1999"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Chemistry"]},{"key":"dc:type","label":"Dc Type","values":["Thesis / Dissertation"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/40005"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Studies have been conducted in synthesising bridged analogues of estradiol in which the ring D hydroxy group is displaced from the 17-position. The aim was to explore the possible rotational equivalence between such analogues and estr~diol. The synthetic routes investigated were based upon cycloaddition to 3-methoxyestra1,3,5(10), 14, 16-pentaene. In the first phase of the project, two approaches for the synthesis of this diene were explored. The first entailed the vinylogous Shapiro elimination of the tosylhydrazone of 3-methoxyestra-1,3,5(10),15-tetraen-17-one to give the 14,16-diene. The second involved conversion of 3-methoxyestra1,3,5(10), 15-tetraen-17-one into the corresponding dienyl triflate, followed by palladium(0) mediated deoxygenation to afford the 14, 16-diene. Of these two methods, only the latter was successful, as the tosylhydrazone of 3-methoxyestra1,3,5(10), 15-tetraen-17-one could not be synthesised. In the second phase of the work~ cycloaddition of 2-chloroacrylonitrile to the 14,16- diene, followed by alkaline hydrolysis afforded 3-methoxy-14, 17a.-ethenoestra- , 1,3,5(10)-trien-15-one and 3-methoxy-14, l 7a.-ethenoestra-l ,3,5(1 0)-trien-16-one, with the 15-ketone as the major isomer. Treatment of these ketones with LSelectride® afforded 3-methoxy-14, 17a.-ethenoestra-l ,3,5(10)-trien-15P-ol and 3- methoxy-14, 17 a.-ethenoestra-1,3 ,5(1 0)-trien-16P-oL Standard deprotection afforded the corresponding diols which were submitted for biological evaluation. An approach towards the corresponding a-alcohols which was investigated is based upon the Baeyer-Villiger oxidation of 16a.-acetyl-3-methoxy-l 4, 17a.-ethenoestra1,3,5(10)-triene. This compound was obtained as the minor product of the boron trifluoride mediated reaction between the 14, 16-diene and methyl vinyl ketone (MVK). The major compound was formulated 16a.-acetyl-3-methoxy-17P-3'- oxobutyl-14, l 7a.-ethenoestra-1,3,5(10)-triene, on the basis of the available spectral data. Reaction of MVK and the 14,16-diene under thermal conditions afforded the desired 16a.-acetyl compound as the major product. Attempts to perform the peracid mediated insertion ofoxygen were unsuccessful. The final phase of the work w"]},{"key":"dc:title","label":"Title","values":["Design and synthesis of rotational analogues of estradiol"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bull, J.R"],"dc:creator":["Seymour, Anthony James"],"dc:date.accessioned":["2024-06-20T12:51:18Z"],"dc:date.available":["2024-06-20T12:51:18Z"],"dc:date.issued":["1999"],"dc:description.abstract":["Studies have been conducted in synthesising bridged analogues of estradiol in which the ring D hydroxy group is displaced from the 17-position. The aim was to explore the possible rotational equivalence between such analogues and estr~diol. The synthetic routes investigated were based upon cycloaddition to 3-methoxyestra1,3,5(10), 14, 16-pentaene. In the first phase of the project, two approaches for the synthesis of this diene were explored. The first entailed the vinylogous Shapiro elimination of the tosylhydrazone of 3-methoxyestra-1,3,5(10),15-tetraen-17-one to give the 14,16-diene. The second involved conversion of 3-methoxyestra1,3,5(10), 15-tetraen-17-one into the corresponding dienyl triflate, followed by palladium(0) mediated deoxygenation to afford the 14, 16-diene. Of these two methods, only the latter was successful, as the tosylhydrazone of 3-methoxyestra1,3,5(10), 15-tetraen-17-one could not be synthesised. In the second phase of the work~ cycloaddition of 2-chloroacrylonitrile to the 14,16- diene, followed by alkaline hydrolysis afforded 3-methoxy-14, 17a.-ethenoestra- , 1,3,5(10)-trien-15-one and 3-methoxy-14, l 7a.-ethenoestra-l ,3,5(1 0)-trien-16-one, with the 15-ketone as the major isomer. Treatment of these ketones with LSelectride® afforded 3-methoxy-14, 17a.-ethenoestra-l ,3,5(10)-trien-15P-ol and 3- methoxy-14, 17 a.-ethenoestra-1,3 ,5(1 0)-trien-16P-oL Standard deprotection afforded the corresponding diols which were submitted for biological evaluation. An approach towards the corresponding a-alcohols which was investigated is based upon the Baeyer-Villiger oxidation of 16a.-acetyl-3-methoxy-l 4, 17a.-ethenoestra1,3,5(10)-triene. This compound was obtained as the minor product of the boron trifluoride mediated reaction between the 14, 16-diene and methyl vinyl ketone (MVK). The major compound was formulated 16a.-acetyl-3-methoxy-17P-3'- oxobutyl-14, l 7a.-ethenoestra-1,3,5(10)-triene, on the basis of the available spectral data. Reaction of MVK and the 14,16-diene under thermal conditions afforded the desired 16a.-acetyl compound as the major product. Attempts to perform the peracid mediated insertion ofoxygen were unsuccessful. The final phase of the work w"],"dc:identifier.uri":["http://hdl.handle.net/11427/40005"],"dc:publisher.department":["Department of Chemistry"],"dc:subject":["Chemistry"],"dc:title":["Design and synthesis of rotational analogues of estradiol"],"dc:type":["Thesis / Dissertation"],"dc:type.qualificationlevel":["Masters"]},"updated_at":"2026-07-22T22:22:39Z"}