UCD School of Chemistry & Chemical Biology

Our research group focuses on synthetic organic chemistry, with interests in both the development of asymmetric synthetic methodology through the application of new chiral ligands in homogeneous metal-catalysed transformations and in the total synthesis of compounds of biological interest.

The preparation of enantiomerically pure compounds is an important area of contemporary synthetic organic chemistry with the market for dosage forms of single enantiomer drugs predicted to rise to $200 billion by 2008. Asymmetric catalysis, one approach for their preparation and the focus of research in both academia and industry, is a technology that is attractive both economically and environmentally. The preparation of new ligands that influence the stereochemistry of reactions occurring at the metal template to which they are complexed is a current focus in our group. We have developed a range of bidentate [N,N] , [N,O] and [P,N] ligands exemplified by structures 1-4, and applied them to the synthetically important asymmetric transformations of the Heck reaction (both intermolecular and intramolecular examples with enantiomeric excesses (ees) up to 99%), allylic substitutions (ees up to 98%), transfer hydrogenation of ketones (up to 96% ee) and rhodium-catalysed hydroboration of alkenes (up to 99.5% ee), Figures 1,2.

Lipoxins are a group of biologically active mediators derived from arachidonic acid through the action of lipoxygenase enzyme systems. Single-cell types generate lipoxins at nanogram levels during human neutrophil-platelet and eisonophil transcellular biosynthesis of eicosanoids, a class of well known biologically active products. Lipoxins are conjugated tetraene-containing eicosanoids and recent results suggest that they are associated with human disease as they modulate cellular events in several organ systems. Lipoxin A4 (LXA4) (7) and lipoxin B4 (LXB4) (8) are the two major lipoxins, Fig. 4. LXA4 (7) has been identified in bronchoalveolar lavage cells while a defect in LXA4) (7) production is observed with cells from patients with chronic myeloid leukaemia. In light of the biological activity associated with this relatively new class of regulators their total synthesis is actively investigated by a range of workers worldwide. Our work aims to prepare Lipoxin analogues with an active region for biological activity but which resist, or more slowly undergo metabolism and therefore have a longer pharmacological activity. The design feature will also take into account that the analogues should be more lipophilic than the natural lipoxins and therefore are more readily taken up by biological membranes. We also have a long-standing interest in the chemistry and biology of amphetamines and substituted MDMA analogues exemplified by 4-MTA (4-methylthioamphetamine 9).