The synthesis of derivatives of naturally occurring naphthalenes

 

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dc.contributor.advisor Giles, Robin G F en_ZA
dc.contributor.author Knight, Lorraine Shirley en_ZA
dc.date.accessioned 2016-02-17T07:16:24Z
dc.date.available 2016-02-17T07:16:24Z
dc.date.issued 1988 en_ZA
dc.identifier.citation Knight, L. 1988. The synthesis of derivatives of naturally occurring naphthalenes. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/17082
dc.description Includes bibliographical references. en_ZA
dc.description.abstract The ansamycins are a large group of natural products which have attracted considerable attention, largely as a result of their range of biological activity. The laboratory synthesis of an ansamycin has been simplified into the independent construction of the aromatic nucleus and the ansa chain, followed by their combination to form the macrocyle. The project described in Chapter 1 was designed to devise a novel, convenient, and efficient synthesis of a substituted 1,4-naphthoquinone which would function as a model for the naphthoquinonoid nucleus of the rifamycin subclass of these antibiotics. In this synthesis, 1,4-benzoquinone was converted into 8- acetyl-5,7-dihydroxy-6-methyl-3-propionylamino-1,4-naphthoquinone in six steps in an overall yield of 20%. The key step in this reaction sequence was the introduction of the C-6 methyl group via a regioselective lithiation/methylation reaction. Compounds which can be structurally defined as bioreductive alkylating agents have considerable potential as antineoplastic agents, according to H.W. Moore (Science, 1977). The protoaphins possess certain structural features which suggest their capability to function as such alkylating agents. Reductive cleavage of the aphid pigment, protoaphin-fb has been shown to give quinone A together with glucoside B, while protoaphin-sl on similar treatment affords quinone A', epimeric with quinone A at C-4, together with the same glucoside B. Professor Giles and co-workers have synthesised the 7,9-dideoxyquinone derivatives of both quinone A and A', as well as quinone A and A' themselves. The second chapter in this thesis describes three different approaches to the synthesis of a 4,10-dihydroxy-7,9-dimethoxy- 1,3-dimethyl-1H-naphtho[2,3-c]pyran analogous to glucoside B. The first two routes describe the construction of a naphtho[ 2,3-c]pyran of the correct relative stereochemistry using the novel reactions pioneered in this Department during the synthesis of 7,9-dideoxyquinone A. In the first method, the pyran ring was constructed with a C-5 oxygen substituent which was subsequently removed. The second method however, differs substantially from this route in that the C-5 substituent was not present during ring closure, hence eliminating the need to remove it at a later stage. The key step in the third approach involved the isomerisation of a dioxolane substituted naphthalene by an intramolecular version of the Mukaiyama reaction. Treatment of a C-8 brominated dioxolanyl naphthalene with titanium tetrachloride resulted in the formation of two angular naphtho[l,2-c]pyrans with the same relative stereochemistry of the pyran ring. An interesting bromine migration occurred after isomerisation had taken place. However, it is suggested that decreasing the size of the C-4 protecting group on the naphthalene nucleus prior to isomerisation, may allow the formation of the linear naphthopyran. en_ZA
dc.language.iso eng en_ZA
dc.subject.other Chemistry en_ZA
dc.subject.other Naphthalene en_ZA
dc.subject.other Rifomycin en_ZA
dc.title The synthesis of derivatives of naturally occurring naphthalenes en_ZA
dc.type Doctoral Thesis
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Science en_ZA
dc.publisher.department Department of Chemistry en_ZA
dc.type.qualificationlevel Doctoral
dc.type.qualificationname PhD en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Knight, L. S. (1988). <i>The synthesis of derivatives of naturally occurring naphthalenes</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/17082 en_ZA
dc.identifier.chicagocitation Knight, Lorraine Shirley. <i>"The synthesis of derivatives of naturally occurring naphthalenes."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 1988. http://hdl.handle.net/11427/17082 en_ZA
dc.identifier.vancouvercitation Knight LS. The synthesis of derivatives of naturally occurring naphthalenes. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 1988 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/17082 en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Knight, Lorraine Shirley AB - The ansamycins are a large group of natural products which have attracted considerable attention, largely as a result of their range of biological activity. The laboratory synthesis of an ansamycin has been simplified into the independent construction of the aromatic nucleus and the ansa chain, followed by their combination to form the macrocyle. The project described in Chapter 1 was designed to devise a novel, convenient, and efficient synthesis of a substituted 1,4-naphthoquinone which would function as a model for the naphthoquinonoid nucleus of the rifamycin subclass of these antibiotics. In this synthesis, 1,4-benzoquinone was converted into 8- acetyl-5,7-dihydroxy-6-methyl-3-propionylamino-1,4-naphthoquinone in six steps in an overall yield of 20%. The key step in this reaction sequence was the introduction of the C-6 methyl group via a regioselective lithiation/methylation reaction. Compounds which can be structurally defined as bioreductive alkylating agents have considerable potential as antineoplastic agents, according to H.W. Moore (Science, 1977). The protoaphins possess certain structural features which suggest their capability to function as such alkylating agents. Reductive cleavage of the aphid pigment, protoaphin-fb has been shown to give quinone A together with glucoside B, while protoaphin-sl on similar treatment affords quinone A', epimeric with quinone A at C-4, together with the same glucoside B. Professor Giles and co-workers have synthesised the 7,9-dideoxyquinone derivatives of both quinone A and A', as well as quinone A and A' themselves. The second chapter in this thesis describes three different approaches to the synthesis of a 4,10-dihydroxy-7,9-dimethoxy- 1,3-dimethyl-1H-naphtho[2,3-c]pyran analogous to glucoside B. The first two routes describe the construction of a naphtho[ 2,3-c]pyran of the correct relative stereochemistry using the novel reactions pioneered in this Department during the synthesis of 7,9-dideoxyquinone A. In the first method, the pyran ring was constructed with a C-5 oxygen substituent which was subsequently removed. The second method however, differs substantially from this route in that the C-5 substituent was not present during ring closure, hence eliminating the need to remove it at a later stage. The key step in the third approach involved the isomerisation of a dioxolane substituted naphthalene by an intramolecular version of the Mukaiyama reaction. Treatment of a C-8 brominated dioxolanyl naphthalene with titanium tetrachloride resulted in the formation of two angular naphtho[l,2-c]pyrans with the same relative stereochemistry of the pyran ring. An interesting bromine migration occurred after isomerisation had taken place. However, it is suggested that decreasing the size of the C-4 protecting group on the naphthalene nucleus prior to isomerisation, may allow the formation of the linear naphthopyran. DA - 1988 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1988 T1 - The synthesis of derivatives of naturally occurring naphthalenes TI - The synthesis of derivatives of naturally occurring naphthalenes UR - http://hdl.handle.net/11427/17082 ER - en_ZA


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