trans-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. <b>Chapter 1: Introduction</b> This chapter reviews methods for the synthesis of trans-2,5-disubstituted tetrahydrofurans with a special emphasis on those that have been applied towards the synthesis of natural products. <b>Chapter 2: Results and Discussion</b> The Acyloin Coupling Reaction towards trans-THFs 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 trans-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 bis-enolate intermediate. Desymmetrisation Using Sharpless Asymmetric Epoxidation towards trans-THFs Strategy developed towards the synthesis of a 2,5-disubstituted 3-hydroxy trans-THF is studied. The optimisation of the synthesis of meso-hepta-1,6-diene-3,5-diol was examined and subsequent desymmetrisation using the Sharpless asymmetric epoxidation was explored. Approaches towards the FG Fragment of Pectenotoxin-4 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. <b>Chapter 3: Experimental</b> Full experimental procedures and characterisation of compounds are reported.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:635206 |
| Date | January 2013 |
| Creators | Tucker, Michael J. |
| Contributors | Donohoe, Timothy J. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:c66ef745-df60-47a3-a167-5046fdb2a50e |
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