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Title: Synthetic studies on halogenated metabolites from Laurencia species
Author: Bonney, Karl James
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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This thesis is presented in three parts: the first entitled “Proposal and Validation of an Alternative Biogenesis for Halogenated Medium-Ring Ethers From Laurencia Species”; the second “Towards the Total Synthesis of the Obtusallene Natural Products”; and the third provides experimental details and characterising data for compounds. Laurencia, which is a species of marine red algae produces an astonishingly diverse array of halogenated acetogenic natural products, including 7-, 8- and 9-membered medium-ring ethers, as well 11- and 12-membered ether-containing macrocycles. Part I of this thesis provides an alternative biogenesis to the long-standing Irie-Murai biogenesis for the halogenated medium-ring ether natural products. The Irie-Murai biogenesis proposes that diol containing compounds undergo an electrophilic bromoetherification reaction to produce the various compounds, whereas we instead postulate that the compounds arise from electrophilic bromonium ion-assisted ring-opening of an enantiopure epoxide. Some initial studies on a model system for the key bromonium ion-assisted epoxide ringopening reaction are described, including an interesting concentration effect. The synthesis of an enantioenriched epoxy-diene precursor to cyclisation is discussed, where a regioselective asymmetric homoallylic epoxidation reaction was required. Some initial unsuccessful cyclisation attempts are presented, as is a successful cyclisation in which bromine-containing 7-, 8- and 9- membered ring-ethers were produced, which represent the core motifs of 5 structurally-diverse natural products. Initial studies to prepare the novel β,γ-epoxy-enyne motif which is found in our proposed biogenetic precursor are also described, culminating in the synthesis of a model system. Part II of this thesis is a continuation of on-going work within this group towards the total synthesis of the obtusallene family of natural products, the halogenated macrocyclic natural products mentioned above. The gram-scale optimisation of reactions involving late-stage intermediates in the total synthesis of obtusallenes II and IV is described. This includes improving the reproducibility of a biomimetic bromoetherification reaction, as well as providing insight into the mechanism of an interesting cyanation reaction which is a synthetically-useful adaptation of a known procedure. Also, an interesting diastereomer-dependent and catalyst-dependent ring-closing metathesis reaction is discussed. Synthetic routes to highly advanced macrocyclic intermediates in the synthesis of obtusallenes II and IV have now been firmly established.
Supervisor: Braddock, Chris Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available