| Summary: | <p><strong>Chapter 1</strong> introduces the synthesis of natural products and the <em>Daphniphyllum</em> family of alkaloids. Prior literature syntheses of these natural products are described as well as our own group’s efforts. The daphlongeranine sub-family are introduced and our previous campaign towards these molecules is summarised.</p>
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<p><strong>Chapter 2</strong> describes a redesigned strategy towards the natural product daphlongeranine B. Multiple competing strategies are investigated before successfully developing an efficient route to the racemic pentacycle of daphlongeranine B. This strategy hinges upon a Michael addition followed by a Claisen rearrangement and ring-closing metathesis to establish three rings.</p>
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<p><strong>Chapter 3</strong> solves two outstanding problems with the synthesis: a site of peripheral oxidation on the pyrrolidine ring and the introduction of enantioselectivity in the synthesis. Following a concerted investigation into C−H oxidation for the former and a transfer of chirality approach for the latter, a Baker’s yeast reduction is adopted as an efficient route towards an enantioenriched, oxidised pyrrolidine building block which is advanced to a pentacyclic intermediate.</p>
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<p><strong>Chapter 4</strong> advances from this enantioenriched intermediate and focuses on the re-positioning of an alkene and the installation of the final all-carbon quaternary centre. From this point, attention turns to the final ring and, grappling with unprecedented levels of steric hindrance, a successful route is developed which employs the intramolecular S<sub>N</sub>2 reaction of an alkyl triflate with a carboxylic acid.</p>
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<p><strong>Chapter 5</strong> focuses on the natural product madangamine E. This additional chapter describes the completion of its total synthesis, advancing from a 25-step intermediate to install the final 11-membered ring in an efficient 5-step sequence.</p>
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