TSASPERA · Total Synthesis of (+)-Aspercyclide A and Analogues

The incidence of allergic disease, from hay fever to asthma and anaphylactic shock, is increasing world-wide, nowhere more than in the UK where it has risen three-fold in 20 years and is now the highest in the world. Allergies including asthma afflict 40% of the UK population and bronchial asthma currently affects 5.2 million. The yearly cost to the UK National Health System in primary care alone exceeds €1,200M, and the loss of 18 million working days costs a further €1,400M. The quality of life for many sufferers is severely impaired. Historical medications (e.g. steroids) simply alleviate the side effects of allergy and are associated with debilitating side-effects. Recently, the humanised monoclonal antibody Zolair® has been approved for treatment of chronic asthma; this acts by inhibiting a specific protein-protein interaction (PPI) common to all allergic responses and is very effective but it is highly expensive and is administered via injection in a regime that is unsustainable for many body sizes. This research is aimed at the development of new a series of small, drug-like molecules based on a natural product lead as potential anti-asthma therapeutic leads with the same mode of action as Zolair®. The molecules will be prepared by synthesis and tested for activity in Enzyme-Linked Immunosorbent Assay (ELISA) and Surface Plasmon Resonance (SPR) assays and promising candidates subjected to co-crystallisation studies with their protein partner.