Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4
<p><em>trans</em>-2,5-Disubstituted tetrahydrofurans (THFs) are a common structural motif in a multitude of biologically active natural products. This thesis explores new synthetic routes for their synthesis and subsequent application towards the C<sub>31-40</sub> fragm...
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| Format: | Thesis |
| Language: | English |
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2013
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| _version_ | 1797112848418078720 |
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| author | Tucker, MJ |
| author2 | Donohoe, TJ |
| author_facet | Donohoe, TJ Tucker, MJ |
| author_sort | Tucker, MJ |
| collection | OXFORD |
| description | <p><em>trans</em>-2,5-Disubstituted tetrahydrofurans (THFs) are a common structural motif in a multitude of biologically active natural products. This thesis explores new synthetic routes for their synthesis and subsequent application towards the C<sub>31-40</sub> fragment of pectenotoxin-4.</p> <p><b>Chapter 1: Introduction</b> This chapter reviews methods for the synthesis of <em>trans</em>-2,5-disubstituted tetrahydrofurans with a special emphasis on those that have been applied towards the synthesis of natural products.</p> <p><b>Chapter 2: Results and Discussion</b> <em>The Acyloin Coupling Reaction towards trans-THFs</em> A brief overview of the acyloin coupling reaction is followed by description of the aim for this part of the project, using this process as a key step towards <em>trans</em>-THFs. Work directed towards the stereoselective protonation of the bis-enolate intermediate formed during the acyloin coupling is discussed. The exploitation of A<sup>1,3</sup> strain was the most effective strategy found to control the diastereoselectivity in the protonation of the <em>bis</em>-enolate intermediate.</p> <p><em>Desymmetrisation Using Sharpless Asymmetric Epoxidation towards trans-THFs</em> Strategy developed towards the synthesis of a 2,5-disubstituted 3-hydroxy <em>trans</em>-THF is studied. The optimisation of the synthesis of <em>meso</em>-hepta-1,6-diene-3,5-diol was examined and subsequent desymmetrisation using the Sharpless asymmetric epoxidation was explored.</p> <p><em>Approaches towards the FG Fragment of Pectenotoxin-4</em> The previous synthesis of the FG fragment was reviewed. Details of the retrosynthesis to be employed for the preparation of the southern hemisphere of pectenotoxin-4 are discussed. The desymmetrisation strategy previously explored was applied towards forming the F ring of pectenotoxin-4. The C<sub>31-40</sub> carbon skeleton was successfully formed in 12 steps using a convergent synthesis. The elucidation of an X-ray crystal structure requires further exploration to confirm the relative and absolute configuration of the THF formed.</p> <p><b>Chapter 3: Experimental</b> Full experimental procedures and characterisation of compounds are reported.</p> |
| first_indexed | 2024-03-07T04:06:45Z |
| format | Thesis |
| id | oxford-uuid:c66ef745-df60-47a3-a167-5046fdb2a50e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-09T03:55:19Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:c66ef745-df60-47a3-a167-5046fdb2a50e2024-03-07T15:30:19ZNovel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4Thesishttp://purl.org/coar/resource_type/c_db06uuid:c66ef745-df60-47a3-a167-5046fdb2a50eOrganic chemistryOrganic synthesisEnglishOxford University Research Archive - Valet2013Tucker, MJDonohoe, TJ<p><em>trans</em>-2,5-Disubstituted tetrahydrofurans (THFs) are a common structural motif in a multitude of biologically active natural products. This thesis explores new synthetic routes for their synthesis and subsequent application towards the C<sub>31-40</sub> fragment of pectenotoxin-4.</p> <p><b>Chapter 1: Introduction</b> This chapter reviews methods for the synthesis of <em>trans</em>-2,5-disubstituted tetrahydrofurans with a special emphasis on those that have been applied towards the synthesis of natural products.</p> <p><b>Chapter 2: Results and Discussion</b> <em>The Acyloin Coupling Reaction towards trans-THFs</em> A brief overview of the acyloin coupling reaction is followed by description of the aim for this part of the project, using this process as a key step towards <em>trans</em>-THFs. Work directed towards the stereoselective protonation of the bis-enolate intermediate formed during the acyloin coupling is discussed. The exploitation of A<sup>1,3</sup> strain was the most effective strategy found to control the diastereoselectivity in the protonation of the <em>bis</em>-enolate intermediate.</p> <p><em>Desymmetrisation Using Sharpless Asymmetric Epoxidation towards trans-THFs</em> Strategy developed towards the synthesis of a 2,5-disubstituted 3-hydroxy <em>trans</em>-THF is studied. The optimisation of the synthesis of <em>meso</em>-hepta-1,6-diene-3,5-diol was examined and subsequent desymmetrisation using the Sharpless asymmetric epoxidation was explored.</p> <p><em>Approaches towards the FG Fragment of Pectenotoxin-4</em> The previous synthesis of the FG fragment was reviewed. Details of the retrosynthesis to be employed for the preparation of the southern hemisphere of pectenotoxin-4 are discussed. The desymmetrisation strategy previously explored was applied towards forming the F ring of pectenotoxin-4. The C<sub>31-40</sub> carbon skeleton was successfully formed in 12 steps using a convergent synthesis. The elucidation of an X-ray crystal structure requires further exploration to confirm the relative and absolute configuration of the THF formed.</p> <p><b>Chapter 3: Experimental</b> Full experimental procedures and characterisation of compounds are reported.</p> |
| spellingShingle | Organic chemistry Organic synthesis Tucker, MJ Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title | Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title_full | Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title_fullStr | Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title_full_unstemmed | Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title_short | Novel synthetic routes towards trans-THFs and application towards the FG fragment of pectenotoxin-4 |
| title_sort | novel synthetic routes towards trans thfs and application towards the fg fragment of pectenotoxin 4 |
| topic | Organic chemistry Organic synthesis |
| work_keys_str_mv | AT tuckermj novelsyntheticroutestowardstransthfsandapplicationtowardsthefgfragmentofpectenotoxin4 |