Synthesis and reactivity of [3.1.1]propellane
In this thesis, the question about reactivity and character of a higher propellane, [3.1.1]Propellane (TCHep), is posed which was so far only synthesised on milligram scale. Chapter 1 gives an introduction into strained molecules, especially the reactivity of the well-explored [1.1.1]propellane and...
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| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1797108301230505984 |
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| author | Frank, N |
| author2 | Anderson, E |
| author_facet | Anderson, E Frank, N |
| author_sort | Frank, N |
| collection | OXFORD |
| description | In this thesis, the question about reactivity and character of a higher propellane, [3.1.1]Propellane (TCHep), is posed which was so far only synthesised on milligram scale. Chapter 1 gives an introduction into strained molecules, especially the reactivity of the well-explored [1.1.1]propellane and bioisosteres in a medicinal chemistry context. In Chapter 2 a novel multigram scale synthesis of TCHep is developed. This made exploration of the chemistry of TCHep possible for which a scope on a variety of reliable reactions is prepared yielding bridgeheaded substituted bicyclo[3.1.1]heptanes (BCHep). Chapter 2 continues with computational and mechanistic approaches to decipher characteristic differences between TCP and TCHep. Chapter 3 recognises that the BCHep substitution pattern maps precisely onto the geometry of meta-substituted benzenes. Functionalisation reactions of BCHep iodides were explored. The BCHep-pharmaceutical analogues of Sonidegib and URB597 were prepared. These drugs revealed enhanced ADME properties to their parent drugs, validating the potential of this meta-arene analogue as an sp3-rich motif in drug design. |
| first_indexed | 2024-03-07T07:27:14Z |
| format | Thesis |
| id | oxford-uuid:537c2ded-3eb4-4df3-b4a4-b5ebef0873b8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:27:14Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:537c2ded-3eb4-4df3-b4a4-b5ebef0873b82022-11-23T10:09:31ZSynthesis and reactivity of [3.1.1]propellaneThesishttp://purl.org/coar/resource_type/c_bdccuuid:537c2ded-3eb4-4df3-b4a4-b5ebef0873b8Computational chemistryChemistry, OrganicEnglishHyrax Deposit2022Frank, NAnderson, EIn this thesis, the question about reactivity and character of a higher propellane, [3.1.1]Propellane (TCHep), is posed which was so far only synthesised on milligram scale. Chapter 1 gives an introduction into strained molecules, especially the reactivity of the well-explored [1.1.1]propellane and bioisosteres in a medicinal chemistry context. In Chapter 2 a novel multigram scale synthesis of TCHep is developed. This made exploration of the chemistry of TCHep possible for which a scope on a variety of reliable reactions is prepared yielding bridgeheaded substituted bicyclo[3.1.1]heptanes (BCHep). Chapter 2 continues with computational and mechanistic approaches to decipher characteristic differences between TCP and TCHep. Chapter 3 recognises that the BCHep substitution pattern maps precisely onto the geometry of meta-substituted benzenes. Functionalisation reactions of BCHep iodides were explored. The BCHep-pharmaceutical analogues of Sonidegib and URB597 were prepared. These drugs revealed enhanced ADME properties to their parent drugs, validating the potential of this meta-arene analogue as an sp3-rich motif in drug design. |
| spellingShingle | Computational chemistry Chemistry, Organic Frank, N Synthesis and reactivity of [3.1.1]propellane |
| title | Synthesis and reactivity of [3.1.1]propellane |
| title_full | Synthesis and reactivity of [3.1.1]propellane |
| title_fullStr | Synthesis and reactivity of [3.1.1]propellane |
| title_full_unstemmed | Synthesis and reactivity of [3.1.1]propellane |
| title_short | Synthesis and reactivity of [3.1.1]propellane |
| title_sort | synthesis and reactivity of 3 1 1 propellane |
| topic | Computational chemistry Chemistry, Organic |
| work_keys_str_mv | AT frankn synthesisandreactivityof311propellane |