{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/21999"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/21999","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Stereoselective synthesis of perhydrobenzo[4.5.6]cholestanes","abstract":"An intramolecular Michael-aldol reaction sequence has been developed for the stereocontrolled synthesis of pentacyclic steroids! with the new six-membered ring attached to the C(4) and C(6) positions. Cholesterol was converted into 3β-hydroxycholest-4-en-6-one by standard methods, and the corresponding 3α-isomer was obtained through Mitsunobu inversion. Acetoacetylation of the 3-alcohols afforded the corresponding 3β- and 3α-acetoacetoxycholest-4-en-6-ones, which served as substrates for an investigation of intramolecular condensation routes to the target ring systems. Base treatment of the 3β-ester resulted in an efficient and stereocontrolled intramolecular Michael addition to give (2R)-2-(3β-hydroxy- 6-oxo-5β-cholestan-4β-yl)-3-oxobutanoic acid 1,3'-lactone, and reaction conditions were developed to achieve sequential lactone cleavage, decarboxylation, and aldol closure, leading to 3β,6-dihydroxy- 4α,4',5β,6β-tetrahydrobenzo[4.5.6]cholestan-5'(6'H)-one. Although this product resisted base-mediated B-elimination, acid treatment resulted in dehydration to give the corresponding Δ⁶-compound. which underwent double bond isomerisation and 5-epimerisation. to give 3β-hydroxy- 4α,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. A similar series of reactions was performed on the 3α-acetoacetate, leading finally to formation of 3α-hydroxy-4β,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. Modification of foregoing reaction conditions, resulted in the design of a tandem Michael-aldol sequence, in which the 3-acetoacetates could be converted directly into the corresponding pentacyclic enones. These products were interrelated via base-mediated equ1llbration of their respective 3,6-diketones, leading to the thermodynamically favoured 4β,5α-isomer. Preliminary investigations into the stereoselective reduction of the olefinic bond in the 4α.5α-isomer, resulted in the formation of a new class of. hexahydrobenzo[4.5.6]cholestane derivatives. The structural and conformational properties of the condensation products were studied with the aid of ¹H NMR, ¹³C NMR, and IR spectroscopy.","abstract_html":"An intramolecular Michael-aldol reaction sequence has been developed for the stereocontrolled synthesis of pentacyclic steroids! with the new six-membered ring attached to the C(4) and C(6) positions. Cholesterol was converted into 3β-hydroxycholest-4-en-6-one by standard methods, and the corresponding 3α-isomer was obtained through Mitsunobu inversion. Acetoacetylation of the 3-alcohols afforded the corresponding 3β- and 3α-acetoacetoxycholest-4-en-6-ones, which served as substrates for an investigation of intramolecular condensation routes to the target ring systems. Base treatment of the 3β-ester resulted in an efficient and stereocontrolled intramolecular Michael addition to give (2R)-2-(3β-hydroxy- 6-oxo-5β-cholestan-4β-yl)-3-oxobutanoic acid 1,3'-lactone, and reaction conditions were developed to achieve sequential lactone cleavage, decarboxylation, and aldol closure, leading to 3β,6-dihydroxy- 4α,4',5β,6β-tetrahydrobenzo[4.5.6]cholestan-5'(6'H)-one. Although this product resisted base-mediated B-elimination, acid treatment resulted in dehydration to give the corresponding Δ⁶-compound. which underwent double bond isomerisation and 5-epimerisation. to give 3β-hydroxy- 4α,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. A similar series of reactions was performed on the 3α-acetoacetate, leading finally to formation of 3α-hydroxy-4β,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. Modification of foregoing reaction conditions, resulted in the design of a tandem Michael-aldol sequence, in which the 3-acetoacetates could be converted directly into the corresponding pentacyclic enones. These products were interrelated via base-mediated equ1llbration of their respective 3,6-diketones, leading to the thermodynamically favoured 4β,5α-isomer. Preliminary investigations into the stereoselective reduction of the olefinic bond in the 4α.5α-isomer, resulted in the formation of a new class of. hexahydrobenzo[4.5.6]cholestane derivatives. The structural and conformational properties of the condensation products were studied with the aid of ¹H NMR, ¹³C NMR, and IR spectroscopy.","abstract_has_math":false,"creators":["Borry, Joost"],"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":1992,"date_issued":"1992","date_published":"1992","updated_at":"2026-07-22T22:23:05Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/21999","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":["Borry, Joost"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-09-28T19:09:00Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-09-28T19:09:00Z"]},{"key":"dc:date.issued","label":"Date","values":["1992"]},{"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":["Master Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["MSc"]}]},{"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/11427/21999"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["An intramolecular Michael-aldol reaction sequence has been developed for the stereocontrolled synthesis of pentacyclic steroids! with the new six-membered ring attached to the C(4) and C(6) positions. Cholesterol was converted into 3β-hydroxycholest-4-en-6-one by standard methods, and the corresponding 3α-isomer was obtained through Mitsunobu inversion. Acetoacetylation of the 3-alcohols afforded the corresponding 3β- and 3α-acetoacetoxycholest-4-en-6-ones, which served as substrates for an investigation of intramolecular condensation routes to the target ring systems. Base treatment of the 3β-ester resulted in an efficient and stereocontrolled intramolecular Michael addition to give (2R)-2-(3β-hydroxy- 6-oxo-5β-cholestan-4β-yl)-3-oxobutanoic acid 1,3'-lactone, and reaction conditions were developed to achieve sequential lactone cleavage, decarboxylation, and aldol closure, leading to 3β,6-dihydroxy- 4α,4',5β,6β-tetrahydrobenzo[4.5.6]cholestan-5'(6'H)-one. Although this product resisted base-mediated B-elimination, acid treatment resulted in dehydration to give the corresponding Δ⁶-compound. which underwent double bond isomerisation and 5-epimerisation. to give 3β-hydroxy- 4α,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. A similar series of reactions was performed on the 3α-acetoacetate, leading finally to formation of 3α-hydroxy-4β,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. Modification of foregoing reaction conditions, resulted in the design of a tandem Michael-aldol sequence, in which the 3-acetoacetates could be converted directly into the corresponding pentacyclic enones. These products were interrelated via base-mediated equ1llbration of their respective 3,6-diketones, leading to the thermodynamically favoured 4β,5α-isomer. Preliminary investigations into the stereoselective reduction of the olefinic bond in the 4α.5α-isomer, resulted in the formation of a new class of. hexahydrobenzo[4.5.6]cholestane derivatives. The structural and conformational properties of the condensation products were studied with the aid of ¹H NMR, ¹³C NMR, and IR spectroscopy."]},{"key":"dc:title","label":"Title","values":["Stereoselective synthesis of perhydrobenzo[4.5.6]cholestanes"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bull, James R"],"dc:creator":["Borry, Joost"],"dc:date.accessioned":["2016-09-28T19:09:00Z"],"dc:date.available":["2016-09-28T19:09:00Z"],"dc:date.issued":["1992"],"dc:description.abstract":["An intramolecular Michael-aldol reaction sequence has been developed for the stereocontrolled synthesis of pentacyclic steroids! with the new six-membered ring attached to the C(4) and C(6) positions. Cholesterol was converted into 3β-hydroxycholest-4-en-6-one by standard methods, and the corresponding 3α-isomer was obtained through Mitsunobu inversion. Acetoacetylation of the 3-alcohols afforded the corresponding 3β- and 3α-acetoacetoxycholest-4-en-6-ones, which served as substrates for an investigation of intramolecular condensation routes to the target ring systems. Base treatment of the 3β-ester resulted in an efficient and stereocontrolled intramolecular Michael addition to give (2R)-2-(3β-hydroxy- 6-oxo-5β-cholestan-4β-yl)-3-oxobutanoic acid 1,3'-lactone, and reaction conditions were developed to achieve sequential lactone cleavage, decarboxylation, and aldol closure, leading to 3β,6-dihydroxy- 4α,4',5β,6β-tetrahydrobenzo[4.5.6]cholestan-5'(6'H)-one. Although this product resisted base-mediated B-elimination, acid treatment resulted in dehydration to give the corresponding Δ⁶-compound. which underwent double bond isomerisation and 5-epimerisation. to give 3β-hydroxy- 4α,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. A similar series of reactions was performed on the 3α-acetoacetate, leading finally to formation of 3α-hydroxy-4β,5α-dihydrobenzo[4.5.6]cholestan-5'(6'H)-one. Modification of foregoing reaction conditions, resulted in the design of a tandem Michael-aldol sequence, in which the 3-acetoacetates could be converted directly into the corresponding pentacyclic enones. These products were interrelated via base-mediated equ1llbration of their respective 3,6-diketones, leading to the thermodynamically favoured 4β,5α-isomer. Preliminary investigations into the stereoselective reduction of the olefinic bond in the 4α.5α-isomer, resulted in the formation of a new class of. hexahydrobenzo[4.5.6]cholestane derivatives. The structural and conformational properties of the condensation products were studied with the aid of ¹H NMR, ¹³C NMR, and IR spectroscopy."],"dc:identifier.uri":["http://hdl.handle.net/11427/21999"],"dc:language.iso":["eng"],"dc:publisher.department":["Department of Chemistry"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["Stereoselective synthesis of perhydrobenzo[4.5.6]cholestanes"],"dc:type":["Master Thesis"],"dc:type.qualificationlevel":["Masters"],"dc:type.qualificationname":["MSc"]},"updated_at":"2026-07-22T22:23:05Z"}