Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres
Bridged or caged polycyclic hydrocarbons with well-defined exit vectors are valuable scaffolds for applications in medicinal chemistry. The development of synthetic methods for accessing new 3D building blocks and saturated isosteres of aromatic rings based on these motifs is a topic of significant...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2024
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| Online Access: | https://eprints.nottingham.ac.uk/77934/ |
| _version_ | 1848801038217248768 |
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| author | Smith, Elliot J. |
| author_facet | Smith, Elliot J. |
| author_sort | Smith, Elliot J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Bridged or caged polycyclic hydrocarbons with well-defined exit vectors are valuable scaffolds for applications in medicinal chemistry. The development of synthetic methods for accessing new 3D building blocks and saturated isosteres of aromatic rings based on these motifs is a topic of significant current interest in organic chemistry. Cubane has received considerable attention as a saturated phenyl ring bioisostere, but its lesser-strained valence isomer cuneane has been sparsely explored. Here, we report methodology for the regioselective synthesis of both 2,6- and 1,3- substituted cuneanes from cubanes, with the regioselectivity being dependant on both the electronic character of the cubane substituents and the choice of reaction conditions. Preliminary computational studies were undertaken that suggest cuneanes could act as isosteres of trans-1,4-disubstituted cyclohexanes and meta-substituted phenyl rings. Finally, the synthesis of a cuneane-containing analog of the anticancer drug sonidegib was carried out.
In a follow-on project, preliminary results for another underexplored transformation of cubanes are presented: the direct functionalisation of cubyl C-H bonds via radical methods. |
| first_indexed | 2025-11-14T21:01:06Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-77934 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:01:06Z |
| publishDate | 2024 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-779342025-02-28T15:20:34Z https://eprints.nottingham.ac.uk/77934/ Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres Smith, Elliot J. Bridged or caged polycyclic hydrocarbons with well-defined exit vectors are valuable scaffolds for applications in medicinal chemistry. The development of synthetic methods for accessing new 3D building blocks and saturated isosteres of aromatic rings based on these motifs is a topic of significant current interest in organic chemistry. Cubane has received considerable attention as a saturated phenyl ring bioisostere, but its lesser-strained valence isomer cuneane has been sparsely explored. Here, we report methodology for the regioselective synthesis of both 2,6- and 1,3- substituted cuneanes from cubanes, with the regioselectivity being dependant on both the electronic character of the cubane substituents and the choice of reaction conditions. Preliminary computational studies were undertaken that suggest cuneanes could act as isosteres of trans-1,4-disubstituted cyclohexanes and meta-substituted phenyl rings. Finally, the synthesis of a cuneane-containing analog of the anticancer drug sonidegib was carried out. In a follow-on project, preliminary results for another underexplored transformation of cubanes are presented: the direct functionalisation of cubyl C-H bonds via radical methods. 2024-07-24 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/77934/1/Corrected_Thesis%20-%20EJS%20%2820197931%29.pdf Smith, Elliot J. (2024) Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres. PhD thesis, University of Nottingham. hydrocarbons phenyl rings isosteres |
| spellingShingle | hydrocarbons phenyl rings isosteres Smith, Elliot J. Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title | Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title_full | Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title_fullStr | Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title_full_unstemmed | Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title_short | Silver(I)-Catalysed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres |
| title_sort | silver(i)-catalysed synthesis of cuneanes from cubanes and their investigation as isosteres |
| topic | hydrocarbons phenyl rings isosteres |
| url | https://eprints.nottingham.ac.uk/77934/ |