This thesis details the studies towards the total synthesis of the calyciphylline A-type Daphniphyllum alkaloids, with a particular focus on daphniyunnine D (23). Chapter 1 introduces these biologically and synthetically interesting polycyclic natural products and describes our designed approach towards their synthesis. Separate studies targeting the construction of two tricyclic ring systems have been developed. These provide rapid entry to synthetically versatile intermediates, allowing for the potential synthesis of numerous members of the alkaloid family. Chapter 2 describes the first study which focuses on the construction of the main tricyclic [6‒5‒7] ACD core 172 via a proton transfer/IMDAF reaction cascade as the main step. Large scale synthesis of the precursor to this cascade 164 has allowed for the successful investigation of an asymmetric variant giving rise to an enantioenriched adduct 104. Chapter 3 describes a novel design for the construction of the [7‒5‒5] DEF tricycle common to 100+ Daphniphyllum alkaloids. An IMPKR, double-bond migration, allylic oxygenation protocol was first validated on a model system and later applied in combination with the synthetic route developed in chapter 2 to achieve the construction of the [6‒5‒7‒5‒5] ACDEF pentacycle 249. Chapter 4 focuses on the construction of the piperidine ring B via an intramolecular gold-catalysed 6-exo-trig hydroalkylation. During the development of the route to daphniyunnine D, various intermediates were afforded which were further elaborated to provide appropriate cyclisation substrates for this study. Their synthesis combined with proof of principle experiments for the desired cyclisation conclude this dissertation work.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:627881 |
| Date | January 2014 |
| Creators | Michaelides, Iacovos Neal |
| Contributors | Dixon, Darren 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:e506466b-5954-4245-babe-f7bdc6a022c2 |
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