UCD School of Chemistry & Chemical Biology

We are working on a family of nitrogen-containing compounds, imidazolines, which are easily tunable strong donors and bases. They have great potential as catalysts and ligands in a wide variety of enantioselective reactions. We have prepared a range of enantiopure imidazolines and bisimidazolines using a novel synthetic method developed in our group. We are now exploring their use in asymmetric catalysis and have obtained excellent results in some synthetically useful reactions. Changing the electronic properties and the conformational preferences of the imidazolines, by changing the N1-substituent (easily done using our new synthetic method), caused pronounced changes in the enantioselectivity of some reactions. The potential for easy tuning in this way is an advantage of imidazolines compared to the closely related oxazolines. Many imidazolines have notable biological activity, so the biological evaluation of our new imidazolines will also be of interest.

Organosulfur chemistry
We have a long term interest in developing new synthetic methods using organosulfur compounds. We carried the first systematic studies of the addition of sulfoxide-stabilised anions to a,b-unsaturated carbonyl compounds and obtained excellent stereoselectivity. New reactions, such as the stereoselective conversion of conjugate adducts into lactones and carbocycles, have been developed. The present focus of the research is on applications to total synthesis, particularly of podophyllotoxin, which is a precursor for important anticancer drugs. A short formal total synthesis of (±)-podophyllotoxin has been achieved and work on an enantioselective version is in progress.

Synthesis of biologically active targets
We have developed a new stereoselective method for forming tetralins and related compounds using cationic cyclisations. This reaction is being applied to the development of efficient syntheses of analogues of naturally occurring anti-cancer compounds, and of the pseudopterosins, which are potent anti-inflammatory agents. Some of this work is being carried out in collaboration with fellow members of the Conway Institute, who will test the compounds for biological activity and study their molecular mechanisms of action. We are also working on a novel route to the potent anti-muscarinic compound himbacine.