Synthetic studies on halogenated metabolites from Laurencia species
Author(s)
Bonney, Karl James
Type
Thesis
Abstract
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.
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.
Date Issued
2011-11
Date Awarded
2012-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Braddock, Chris
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)