Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids

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dc.contributor.advisorBull, James Ren_ZA
dc.contributor.authorSickle, Eugene Stanforden_ZA
dc.date.accessioned2016-03-17T12:46:07Z
dc.date.available2016-03-17T12:46:07Z
dc.date.issued1997en_ZA
dc.descriptionIncludes summary.en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractAn efficient strategy for the synthesis of 14β-3'-oxobutyl 19-norsteroids has been developed and the intramolecular reactivity of the derived compounds has been investigated. The approach is based on cycloaddition of methyl vinyl ketone to 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate which proceeded with a high degree of regio- and stereoselectivity to give 16α-acetyl-3-methoxy-14, 17α-ethenoestra-1 ,3,5(1 O)-trien-17β-yl acetate. The cycloadduct underwent base mediated fragmentation, affording an efficient and stereocontrolled synthesis of 3-methoxy-14β-3'-oxobutylestra-1,3,5(10),15-tetraen-17-one which in turn gave 3-methoxy-5',6'-dihydro-15αH-benzo[14,15]-14β-estra-1,3,5(1O)-trien-4'(3'H), 17-dione via an intramolecular Michael reaction. Regioselective deoxygenation of the dione at C-4', followed by standard functional group modifications provided the parent 14β-perhydrobenzo[14,15]-estradiol analogues. An alternative, more expedient, route to this novel steroidal ring system was developed which relied on an anionic oxy-Cope rearrangement as the key step. Thus methylenation of the cycloadducts derived from reaction of the dienyl acetate and selected dienophiles (acrolein and methyl vinyl ketone) gave after hydrolysis of the bridgehead ester, substrates which underwent [3,3]sigmatropic rearrangement to generate a series of 14β-perhydrobenzo[14,15]-17-ketones.en_ZA
dc.identifier.apacitationSickle, E. S. (1997). <i>Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/17967en_ZA
dc.identifier.chicagocitationSickle, Eugene Stanford. <i>"Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 1997. http://hdl.handle.net/11427/17967en_ZA
dc.identifier.citationSickle, E. 1997. Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Sickle, Eugene Stanford AB - An efficient strategy for the synthesis of 14β-3'-oxobutyl 19-norsteroids has been developed and the intramolecular reactivity of the derived compounds has been investigated. The approach is based on cycloaddition of methyl vinyl ketone to 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate which proceeded with a high degree of regio- and stereoselectivity to give 16α-acetyl-3-methoxy-14, 17α-ethenoestra-1 ,3,5(1 O)-trien-17β-yl acetate. The cycloadduct underwent base mediated fragmentation, affording an efficient and stereocontrolled synthesis of 3-methoxy-14β-3'-oxobutylestra-1,3,5(10),15-tetraen-17-one which in turn gave 3-methoxy-5',6'-dihydro-15αH-benzo[14,15]-14β-estra-1,3,5(1O)-trien-4'(3'H), 17-dione via an intramolecular Michael reaction. Regioselective deoxygenation of the dione at C-4', followed by standard functional group modifications provided the parent 14β-perhydrobenzo[14,15]-estradiol analogues. An alternative, more expedient, route to this novel steroidal ring system was developed which relied on an anionic oxy-Cope rearrangement as the key step. Thus methylenation of the cycloadducts derived from reaction of the dienyl acetate and selected dienophiles (acrolein and methyl vinyl ketone) gave after hydrolysis of the bridgehead ester, substrates which underwent [3,3]sigmatropic rearrangement to generate a series of 14β-perhydrobenzo[14,15]-17-ketones. DA - 1997 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1997 T1 - Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids TI - Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids UR - http://hdl.handle.net/11427/17967 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/17967
dc.identifier.vancouvercitationSickle ES. Cycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroids. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 1997 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/17967en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleCycloaddition-fragmentation mediated pathways to ring D modified 19-norsteroidsen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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