Studies in ring D fragmentation of estrone

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dc.contributor.advisorBull, James Ren_ZA
dc.contributor.authorRay, Peter Christopheren_ZA
dc.date.accessioned2016-03-17T12:45:57Z
dc.date.available2016-03-17T12:45:57Z
dc.date.issued1998en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractStudies have been conducted in synthesising 14-allyl 19-norsteroids. The eventual aim is to convert the 14-allyl derivatives into bridge-functionalised 19-norsteroids. Two approaches were investigated, with the immediate aim of generating fragmentation intermediates suitable for 14-allylation. The approaches were based on cleavage of the 16,17-bond via oxidative cleavage or fragmentation methodology. The oxidative cleavage routes involved the preparation of 3-methoxy-17 –methylestra-1,3,5(10), 16-tetraen-15-one, which was shown not to undergo regioselective 14-methylation. In an alternative approach 3-methoxy-17a-methylestra-1,3,5(10),14tetraene- 16β, 17β-diol was synthesised. However, the lability of the primary cleaved product prompted synthesis of 3-methoxy-16,17-seco-17a-homoestra-1,3,5(10)-triene16,17a- dione. Chemodifferentiation of the carbonyl groups of the seco derivative provided access to 16-acetoxy-3-methoxy-16, 17-seco-17a-homoestra-1,3,5(10)-trien-17a-one, in an overall yield of 60% from estrone 3-methyl ether. The fragmentation approaches involved conjugate stannylation and silylation of 3-methoxyestra-1,3,5,(10), 15-tetraen-17 -one to give the 15β-trimethylstannyl and 15β-trimethylsilyl 17 -ketones respectively. The stannyl ketone was converted to the 3-methoxy-17a-methyl-15β-trimethylstannylestra-1,3,5,(10)-trien-l7β-ol. Generation of the derived alkoxy radical resulted in formation of 3-methoxy-16, 17-seco-17a-homoestra1,3,5( 10),15-tetraen-17a-one, in low yield, The silyl ketone was converted to the 17acetoxyimino- 3 -methoxy-15β-trimethylsilylestra-l,3,5( 10)-trien, Fragmentation with the borontrifluoride diethyl ether complex resulted in formation of the undesired 3-methoxy13,17-secoestra-l ,3,5(1 0),l4-tetraen-17-nitrile. Since the 15β-trimethylsilyl group did not direct the fragmentation, the 17-acetoxyimino-3-methoxy-16β-trimethylsilylmethylestra-1,3,5(10)-triene was synthesised in the hope that it would be more amenable to silicon directed fragmentation, However, fragmentation with the boron trifluoride diethyl ether complex resulted In formation of the undesired 17-acetoxy-3-methoxy 16β-trimethylsilylmethyl-17a-aza-17a-homoestra-1,3,5(10), 17-tetraene.en_ZA
dc.identifier.apacitationRay, P. C. (1998). <i>Studies in ring D fragmentation of estrone</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/17964en_ZA
dc.identifier.chicagocitationRay, Peter Christopher. <i>"Studies in ring D fragmentation of estrone."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 1998. http://hdl.handle.net/11427/17964en_ZA
dc.identifier.citationRay, P. 1998. Studies in ring D fragmentation of estrone. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Ray, Peter Christopher AB - Studies have been conducted in synthesising 14-allyl 19-norsteroids. The eventual aim is to convert the 14-allyl derivatives into bridge-functionalised 19-norsteroids. Two approaches were investigated, with the immediate aim of generating fragmentation intermediates suitable for 14-allylation. The approaches were based on cleavage of the 16,17-bond via oxidative cleavage or fragmentation methodology. The oxidative cleavage routes involved the preparation of 3-methoxy-17 –methylestra-1,3,5(10), 16-tetraen-15-one, which was shown not to undergo regioselective 14-methylation. In an alternative approach 3-methoxy-17a-methylestra-1,3,5(10),14tetraene- 16β, 17β-diol was synthesised. However, the lability of the primary cleaved product prompted synthesis of 3-methoxy-16,17-seco-17a-homoestra-1,3,5(10)-triene16,17a- dione. Chemodifferentiation of the carbonyl groups of the seco derivative provided access to 16-acetoxy-3-methoxy-16, 17-seco-17a-homoestra-1,3,5(10)-trien-17a-one, in an overall yield of 60% from estrone 3-methyl ether. The fragmentation approaches involved conjugate stannylation and silylation of 3-methoxyestra-1,3,5,(10), 15-tetraen-17 -one to give the 15β-trimethylstannyl and 15β-trimethylsilyl 17 -ketones respectively. The stannyl ketone was converted to the 3-methoxy-17a-methyl-15β-trimethylstannylestra-1,3,5,(10)-trien-l7β-ol. Generation of the derived alkoxy radical resulted in formation of 3-methoxy-16, 17-seco-17a-homoestra1,3,5( 10),15-tetraen-17a-one, in low yield, The silyl ketone was converted to the 17acetoxyimino- 3 -methoxy-15β-trimethylsilylestra-l,3,5( 10)-trien, Fragmentation with the borontrifluoride diethyl ether complex resulted in formation of the undesired 3-methoxy13,17-secoestra-l ,3,5(1 0),l4-tetraen-17-nitrile. Since the 15β-trimethylsilyl group did not direct the fragmentation, the 17-acetoxyimino-3-methoxy-16β-trimethylsilylmethylestra-1,3,5(10)-triene was synthesised in the hope that it would be more amenable to silicon directed fragmentation, However, fragmentation with the boron trifluoride diethyl ether complex resulted In formation of the undesired 17-acetoxy-3-methoxy 16β-trimethylsilylmethyl-17a-aza-17a-homoestra-1,3,5(10), 17-tetraene. DA - 1998 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1998 T1 - Studies in ring D fragmentation of estrone TI - Studies in ring D fragmentation of estrone UR - http://hdl.handle.net/11427/17964 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/17964
dc.identifier.vancouvercitationRay PC. Studies in ring D fragmentation of estrone. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 1998 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/17964en_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.titleStudies in ring D fragmentation of estroneen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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