Current research

Heterocyclic chemistry, biological chemistry, synthetic organic chemistry, especially synthesis of natural products and substances of biological importance; current targets include muscarinic and sigma receptor ligands, indoles, halogenated lactones, lignans and isoquinolines; fluorous chemistry, automated synthesis and combinatorial chemistry.

Current major projects include:

(i) the synthesis of radiopharmaceuticals for the diagnosis of age-related diseases - with Assoc Prof M. Kassiou (Royal Prince Alfred Hospital and Sydney University).
Parallel approaches have been taken to the design of radiolabelled m2 selective muscarinic ligands that might be used with non-invasive emission tomographic techniques for the diagnosis of early onset dementia. In one strand a versatile synthesis of a key dibenzodiazepinone molecule has been achieved and a range of derivatives prepared and tested before labelling with 123I or 11C (AINSE, 1996; ARC Small, 1997).  High affinity but low selectivity have been observed. The effect of substitution by small heterocyclic rings is under examination at present. Also, a synthesis of analogues of himbacine, a naturally-occurring alkaloid with m2 selective muscarinic antagonist properties, is being developed. Radiolabelling aspects of this research are assisted by Dr Kassiou.

In a new, closely related project, several structural and stereochemical features of trishomocubane, sigma receptor ligands are under investigation. The sigma receptors bind to many recreational drugs, including cocaine, and therefore trishomocubanes have generated interest for their potential as agonists and antagonists and in the study of addiction (ARC DP, 2006-2010).

(ii) the chemistry of natural anti-fouling agents.
This is a highly multidisciplinary project in which fimbrolide natural products, halogenated furanoid substances that have remarkable microbial properties and show profound effects on the N-acyl homoserine lactone mediated bacterial autoinduction system, are being studied from a chemical and biological standpoint.  The two biological responses have enormous economic and social consequences with potential applications in anti-fouling technology and control of virulence in bacteria.  I was invited to join with Professor Staffan Kjelleberg (Microbiology and Immunology) and Dr Peter Steinberg (Biological Sciences) in the establishment of the Centre for Marine Biofouling and BioInnovation, UNSW, in 1996, in order to study these molecules and others like them. This Centre has received multi-million dollar support from institutions and industry, and in 2000 a start-up company, Biosignal, was established to commercialise the Centre's research findings. Biosignal Pty Ltd was floated on the stock exchange in 2004 and I remain a shareholder as co-inventor on a number of its patents.

(iii) synthetic approaches to potential selective estrogen receptor modulators (SERMs).
This industry supported project (ARC SPIRT, 2000-2002) was directed towards establishing efficient methods for the synthesis of naturally derived SERM analogues and involved modern organometallic chemistry designed to be adaptable to combinatorial methods. Current interest is in the application of the more successful approaches to automated synthesis and lead development.

Fluorous Chemistry and Combinatorial Chemistry

A new direction has been set in my research group in the last 5 years. This has involved an interest in the maturing field of combinatorial chemistry. Our interest lies not in simply using known methods or strategies to prepare libraries of compounds, although this is now a useful research technique, but rather to make research contributions that will add to the power of combinatorial methods. Accordingly, we initiated a discovery program, looking into new ways of applying fluorous chemistry to methods of combinatorial synthesis. A first step was to investigate the design and synthesis of new fluorous taggants (ARC Large, 2000-2002) and from this study has emerged an interest in acetal chemistry and dynamic covalent chemistry (ARC DP, 2006-2010). Subsequently, we have expanded our interest towards fluorous reagents, catalyst ligands and surfactants (UNSW URSP, 2002; ARC DP, 2003-2005). My group has acquired considerable expertise in the fluorous field and much of the basic equipment for basic parallel or mixed, solution phase combinatorial synthesis. I have also established a combinatorial research network in the Sydney metropolitan region and have been awarded, with colleagues from Macquarie University and Sydney University, substantial ARC LIEF funding (ARC LIEF, 2002, 2004, 2005) and have consequently assembled equipment for a multi-user Sydney Regional Combinatorial Research Facility, with a major Chemistry Laboratory node at UNSW, in which to work.