The synthesis of substituted tetramates for antibacterial studies
<p><strong>Chapter 1</strong> gives a brief introduction into the history of antibacterial drug discovery, the previous work carried out in the Moloney group in synthesising antibacterial tetramates, and the rationale for this DPhil research project.</p> <p><strong&...
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| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1797109096248246272 |
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| author | Saney, L |
| author2 | Moloney, M |
| author_facet | Moloney, M Saney, L |
| author_sort | Saney, L |
| collection | OXFORD |
| description | <p><strong>Chapter 1</strong> gives a brief introduction into the history of antibacterial drug discovery, the previous work carried out in the Moloney group in synthesising antibacterial tetramates, and the rationale for this DPhil research project.</p>
<p><strong>Chapter 2</strong> describes the synthesis of tetramic acids from threo-phenylserine derivatives. It demonstrates how bicyclic tetramates could be obtained chemoselectively and diastereoselectively. Additionally, it was shown that a library of densely functionalised C7-carboxamidotetramic acids could be synthesised and these compounds have the ability to bind to metal ions and may exhibit tautomeric behaviour in solution.</p>
<p><strong>Chapter 3</strong> describes the synthesis of tetramic acids from erythro-phenylserine derivatives with excellent diastereoselectivity and chemoselectivity observed. Additionally, also described is the synthesis of C7-carboxamides and C7-acyltetramates, where it was shown that these compounds also bind to metal ions and may exhibit tautomeric behaviour in solution. Finally discussed is the diastereoselective reduction of bicyclic tetramates and Suzuki couplings with mesylates to form densely functionalised pyrrolidinone derivatives.</p>
<p><strong>Chapter 4</strong> describes the attempted synthetic methodology of obtaining C2, C4 and C7-functionalised tetramates from threo-phenylserine and allo/threo-phenylcysteine derivatives. Moreover, this chapter describes the synthesis of imidazolidine-derived tetramic acids in a chemoselective and diastereoselective manner, in which the C2 and C4-substituents are readily functionalised. However, a C7-carboxamide library could not be synthesised chemoselectively.</p>
<p><strong>Chapter 5</strong> discusses the antibacterial activity and physicochemical properties of tetramates synthesised. None of the compounds synthesised exhibited any bioactivity against E. coli, however, many compounds exhibited potent antibacterial activity against S. aureus. However, this activity was compromised when tested in the presence of human serum albumin and/or blood.</p> |
| first_indexed | 2024-03-07T07:37:10Z |
| format | Thesis |
| id | oxford-uuid:ea424929-5bdc-48d8-ad07-8e098ea68c66 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:37:10Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:ea424929-5bdc-48d8-ad07-8e098ea68c662023-03-15T14:16:10ZThe synthesis of substituted tetramates for antibacterial studiesThesishttp://purl.org/coar/resource_type/c_db06uuid:ea424929-5bdc-48d8-ad07-8e098ea68c66Chemistry, OrganicEnglishHyrax Deposit2021Saney, LMoloney, M<p><strong>Chapter 1</strong> gives a brief introduction into the history of antibacterial drug discovery, the previous work carried out in the Moloney group in synthesising antibacterial tetramates, and the rationale for this DPhil research project.</p> <p><strong>Chapter 2</strong> describes the synthesis of tetramic acids from threo-phenylserine derivatives. It demonstrates how bicyclic tetramates could be obtained chemoselectively and diastereoselectively. Additionally, it was shown that a library of densely functionalised C7-carboxamidotetramic acids could be synthesised and these compounds have the ability to bind to metal ions and may exhibit tautomeric behaviour in solution.</p> <p><strong>Chapter 3</strong> describes the synthesis of tetramic acids from erythro-phenylserine derivatives with excellent diastereoselectivity and chemoselectivity observed. Additionally, also described is the synthesis of C7-carboxamides and C7-acyltetramates, where it was shown that these compounds also bind to metal ions and may exhibit tautomeric behaviour in solution. Finally discussed is the diastereoselective reduction of bicyclic tetramates and Suzuki couplings with mesylates to form densely functionalised pyrrolidinone derivatives.</p> <p><strong>Chapter 4</strong> describes the attempted synthetic methodology of obtaining C2, C4 and C7-functionalised tetramates from threo-phenylserine and allo/threo-phenylcysteine derivatives. Moreover, this chapter describes the synthesis of imidazolidine-derived tetramic acids in a chemoselective and diastereoselective manner, in which the C2 and C4-substituents are readily functionalised. However, a C7-carboxamide library could not be synthesised chemoselectively.</p> <p><strong>Chapter 5</strong> discusses the antibacterial activity and physicochemical properties of tetramates synthesised. None of the compounds synthesised exhibited any bioactivity against E. coli, however, many compounds exhibited potent antibacterial activity against S. aureus. However, this activity was compromised when tested in the presence of human serum albumin and/or blood.</p> |
| spellingShingle | Chemistry, Organic Saney, L The synthesis of substituted tetramates for antibacterial studies |
| title | The synthesis of substituted tetramates for antibacterial studies |
| title_full | The synthesis of substituted tetramates for antibacterial studies |
| title_fullStr | The synthesis of substituted tetramates for antibacterial studies |
| title_full_unstemmed | The synthesis of substituted tetramates for antibacterial studies |
| title_short | The synthesis of substituted tetramates for antibacterial studies |
| title_sort | synthesis of substituted tetramates for antibacterial studies |
| topic | Chemistry, Organic |
| work_keys_str_mv | AT saneyl thesynthesisofsubstitutedtetramatesforantibacterialstudies AT saneyl synthesisofsubstitutedtetramatesforantibacterialstudies |