Streamlined synthesis of taxol analogues
<p>This thesis centres on the synthesis of taxol analogues via late-stage hydroxylation with P450 enzymes. To accomplish this, the taxane core, specifically taxa-4(5),11(12)-dien-2-one, was synthesised by classical synthetic methods, and subsequently oxidised using P450<sub>BM3</sub&g...
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| Format: | Thesis |
| Language: | English |
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2017
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| _version_ | 1797070005352792064 |
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| author | Rodriguez, P |
| author2 | Robertson, J |
| author_facet | Robertson, J Rodriguez, P |
| author_sort | Rodriguez, P |
| collection | OXFORD |
| description | <p>This thesis centres on the synthesis of taxol analogues via late-stage hydroxylation with P450 enzymes. To accomplish this, the taxane core, specifically taxa-4(5),11(12)-dien-2-one, was synthesised by classical synthetic methods, and subsequently oxidised using P450<sub>BM3</sub> mutants.</p> <p>Chapter 1 introduces enzymatic catalysis, and the advantages and disadvantages of its application to organic synthesis. Additionally, an overview of taxol, including its discovery, mode of action, biosynthesis and large-scale production, and a summary of the previously reported approaches to the taxane core are described.</p> <p>Chapter 2 details the problems encountered and solutions implemented when reproducing Baran’s route to taxa-4(5),11(12)-dien-2-one. Furthermore, approaches to some of its intermediates and an alternative route to taxa-4(5),11(12)-dien-2-one, which is based on Baran’s, are discussed.</p> <p>Chapter 3 describes the development of a new, practical and short synthetic route to taxa-4(5),11(12)-dien-2-one which, ultimately, led to 1,3-di-<em>epi</em>-taxa-4(5),11(12)-dien-2-one. Additionally, the application of this route to the synthesis of a model compound and attempts to convert this racemic synthesis into an enantioselective route are reported.</p> <p>Finally, the enzymatic oxidation of taxa-4(5),11(12)-dien-2-one and related molecules using P450<sub>BM3</sub> mutants is explored in Chapter 4. A preliminary study to determine the substrate enantioselectivity of the mutants is also described, along with the biological assays of the oxidised compounds produced during the study.</p> |
| first_indexed | 2024-03-06T22:32:48Z |
| format | Thesis |
| id | oxford-uuid:58d4a7f3-038e-4c4a-9aec-67267277670f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:32:48Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | oxford-uuid:58d4a7f3-038e-4c4a-9aec-67267277670f2022-03-26T17:06:05ZStreamlined synthesis of taxol analoguesThesishttp://purl.org/coar/resource_type/c_db06uuid:58d4a7f3-038e-4c4a-9aec-67267277670fOrganic compounds--SynthesisEnglishORA Deposit2017Rodriguez, PRobertson, J<p>This thesis centres on the synthesis of taxol analogues via late-stage hydroxylation with P450 enzymes. To accomplish this, the taxane core, specifically taxa-4(5),11(12)-dien-2-one, was synthesised by classical synthetic methods, and subsequently oxidised using P450<sub>BM3</sub> mutants.</p> <p>Chapter 1 introduces enzymatic catalysis, and the advantages and disadvantages of its application to organic synthesis. Additionally, an overview of taxol, including its discovery, mode of action, biosynthesis and large-scale production, and a summary of the previously reported approaches to the taxane core are described.</p> <p>Chapter 2 details the problems encountered and solutions implemented when reproducing Baran’s route to taxa-4(5),11(12)-dien-2-one. Furthermore, approaches to some of its intermediates and an alternative route to taxa-4(5),11(12)-dien-2-one, which is based on Baran’s, are discussed.</p> <p>Chapter 3 describes the development of a new, practical and short synthetic route to taxa-4(5),11(12)-dien-2-one which, ultimately, led to 1,3-di-<em>epi</em>-taxa-4(5),11(12)-dien-2-one. Additionally, the application of this route to the synthesis of a model compound and attempts to convert this racemic synthesis into an enantioselective route are reported.</p> <p>Finally, the enzymatic oxidation of taxa-4(5),11(12)-dien-2-one and related molecules using P450<sub>BM3</sub> mutants is explored in Chapter 4. A preliminary study to determine the substrate enantioselectivity of the mutants is also described, along with the biological assays of the oxidised compounds produced during the study.</p> |
| spellingShingle | Organic compounds--Synthesis Rodriguez, P Streamlined synthesis of taxol analogues |
| title | Streamlined synthesis of taxol analogues |
| title_full | Streamlined synthesis of taxol analogues |
| title_fullStr | Streamlined synthesis of taxol analogues |
| title_full_unstemmed | Streamlined synthesis of taxol analogues |
| title_short | Streamlined synthesis of taxol analogues |
| title_sort | streamlined synthesis of taxol analogues |
| topic | Organic compounds--Synthesis |
| work_keys_str_mv | AT rodriguezp streamlinedsynthesisoftaxolanalogues |