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Organic Chemistry
Organic Synthesis, Methodology and Host-Guest Chemistry
Dr Mick Sherburn
http://rsc.anu.edu.au/research/sherburn.php
Cascade (domino) reactions are
spectacular events in which many bonds are made and broken in a
single step. These reactions hold much promise for achieving more
efficient syntheses: a pressing need in times of increasing
production costs and the importance of protecting the environment by
reducing waste. Our research program involves the design and
implementation of sequences of cycloaddition reactions, free radical
reactions and transition metal-mediated reactions to prepare
polycyclic molecules with important biological properties. This
program also targets new ways to achieve molecular recognition,
complexation and catalysis. Overall, the primary goal is to
synthesise such complex molecules in a practical manner.
Efficient Total Synthesis: Anti-tumour and Anti-Alzheimer's
Natural Products
Lignans
like podophyllotoxin have cancer-fighting properties and are used in
chemotherapy. An efficient and highly modular approach for the
synthesis of these compounds has been developed. This strategy has
several advantages over previous syntheses, the most significant of
which being that it allows a high level of convergency at the end of
the synthetic route.
Himbacine
is natural product isolated from Galbulimima baccata, a
species of tree found in Northern Australia and Papua New Guinea.
Himbacine was found to exhibit strong, selective binding to
muscarinic receptors of the M2 subtype. Speculation that selective
presynaptic muscarinic receptor antagonists might find application in
the treatment of neurodegenerative disorders such as Alzheimer's
disease provoked our interest in Galbulimima alkaloids. A modular
strategy for the synthesis of himbacine and analogues has been
developed. The synthesis draws upon new chemistry developed in other
projects currently under way in the group. (with J. Fischer,
A.J. Scott, L.A. Sharp, L.S.-M. Wong, A.J. Reynolds
[U. Sydney])
The crystal structure of an
analogue of himbacine,
prepared for biological testing
A Deeper Understanding of the Most Important Organic Reaction
The Diels-Alder reaction is one of the most powerful and most commonly
used reactions in synthetic organic chemistry. Predicting,
controlling and explaining the stereochemical outcome of its
intramolecular variant continues to be a major activity within the
group. The location of transition structures at high levels of
theory is providing stimulating new insights into the reaction. This
deeper understanding is driving the development of new methodology.
We have developed a novel, efficient and very general way to produce
complex polycyclic molecules with useful biological properties from
simple, unsaturated, acyclic precursors using a sequence of
intramolecular Diels-Alder reactions. (with T.N. Cayzer,
N. Miller, C.I. Turner, L.S. M. Wong [U. Sydney],
M.N. Paddon-Row [U. NSW])
A computed transition structure along with the X-ray crystal
structure of its corresponding cycloaddition product
Host-guest Chemistry
Research
in this area is concerned with the design and synthesis of host
molecules based upon cavitands (rigid, bowl-shaped molecules) for
molecular recognition, complexation and catalysis. Investigations
into potential uses of these intriguing hosts as molecule-sized
devices is under way. (with E.S. Barrett, J.R. Hansen
[U. Sydney])
A model of one of our hosts (a
bis-bowl molecule, represented in
wire frame format) binding three guest molecules (dichloromethane,
represented as space filling models) in the solid state.
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