The synthesis of derivatives of naturally occurring naphthalenes
| 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.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.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.citation | Knight, L. 1988. The synthesis of derivatives of naturally occurring naphthalenes. University of Cape Town. | 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 |
| dc.identifier.uri | http://hdl.handle.net/11427/17082 | |
| 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.language.iso | eng | en_ZA |
| dc.publisher.department | Department of Chemistry | en_ZA |
| dc.publisher.faculty | Faculty of Science | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| 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 | |
| dc.type.qualificationlevel | Doctoral | |
| dc.type.qualificationname | PhD | en_ZA |
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Thesis | en_ZA |
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