My interests
are concerned with synthetic organic chemistry, particularly
in relation to the synthesis of biologically relevant compounds,
the functionalisation of materials and the development of new
methodology.
Synthesis
of Biologically Relevant Compounds
Pyrrolidine and
piperidine nitrogen heterocycles occur widely in nature, and
are of considerable pharmaceutical and biochemical importance
because of their antibiotic, antibacterial, antifungal and
cytotoxic effects. There is a need for the development of simple,
short, efficient and versatile routes to such heterocycles,
which allow control of both relative and absolute stereochemistry,
to enable the expedient synthesis of natural products, and
related analogues, which have promising biochemical activity.
Our approach
has involved the application of bicyclic lactam templates for
heterocycle synthesis. These compounds offer several important
advantages as synthetic starting materials: they are fully
protected, with a single protecting group, and prepared using
cheap reagents; they are of low molecular weight; they have
potential for ring functionalisation; and they possess a bicyclic
system for stereocontrol. All of these compounds have been
used to access highly functionalised pyrrolidinones and piperidinones,
and work is now underway to apply these compounds in natural
product synthesis and for the construction of compounds of
well-defined molecular architecture. Our
interest is primarily related to novel antibiotics, but also
includes other bioactives, including neurological and anticancer
agents.
Functionalisation
of Materials
This project
uses carbenes as reactive intermediates for the modification
of various materials and polymers; this may be achieved under
thermolytic or photolytic conditions, allowing the incorporation
of functionality (e.g. chromophoric, biocidal or fluorescent
groups) into otherwise inert substrates. This
highly novel approach has proved to be widely applicable, allowing
the conversion of commodity materials into functional materials;
significantly, this modification is achieved only on the surface
of the material, without alteration of its bulk properties. Current
work aims to understand the molecular events involved in the
surface modification, and to explore and develop the scope
of the process.
Development
of New Methodology
Whilst organometallic
compounds derived from transition metals have been extensively
applied to organic synthesis, those of lead(IV) and bismuth(V)
are less so. Why could these metals be so useful? In fact,
they are good electrophiles, have high co-ordination numbers
and oxidation potential, and there is precedent for their application
in oxidation reactions and ligand coupling. However,
the design of ligands for lead(IV), for example, is much more
challenging than for so many other (non-oxidising) metals,
since we require an electron donor which is not readily oxidised;
this restricts substantially the choice of possible functional
groups. We have chosen chelating carboxylates, often with pendant
nitrogen donors, for investigation. Lead tetracarboxylates
derived from monocarboxylic acids and dicarboxylic acids are
readily accessible, by metathesis of lead tetraacetate; this
method allows the preparation of mixed ligand complexes by
appropriate choice of stoichiometry of the desired ligands.
Our specific aim has been to identify ligands which give organic-soluble
lead(IV) systems, capable of reacting both as 2-electron oxidants
and in carbon-carbon bond forming reactions. In
addition to studying their synthesis and reactivity, we have
recently initiated detailed structural studies of many of these
compounds using crystallographic, mass spectroscopic and 207Pb nmr spectroscopic (solution and solid state)
techniques; this has in turn given us a greater understanding
of the reactivity of these lead(IV) compounds.
Selected recent
publications
- “A Chemical Method
for the Surface Functionalisation of Polymers”, K. Awenat,
P.J. Davis, M.G. Moloney, Chem. Commun., 2005, 990 - 992.
- “ Aryldiazirine Modified
Pyroglutamates: Photoaffinity Labels for Glutamate”, E. Bentz,
H. Gibson, C. Hudson, M. G. Moloney, D. A. Seldon, and E.
S. Wearmouth, Synlett., 2006, 247.
- “2,5-Disubstituted
Pyrrolidines: Rapid Stereocontrolled Access from Sulfones”,
M.G. Moloney, T. Panchal, and R. Pike, Org.
Biomol. Chem.,
2006, 3894-3897.
- "Enantioselective Synthesis of Tetramic Acids and
Lactams from Threonine ", M. Anwar and M.G. Moloney, Tetrahedron
Lett., 2007, 48, 7259–7262.
Dr M.G. Moloney