| Summary: | <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>
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