TANDEM · Developing Tandem Reaction Sequences for the Rapid Synthesis of Selected Bioactive Natural Products Followed by Parallel synthesis of analogue libraries and Biological Evaluation

A proposal for the concise synthesis of a family of cytotoxic natural products obtained from Polythia Crassa is contained herein. The short and highly effcient synthesis accesses all the structurally diverse family members from two simple common precursors. The synthesis makes use of novel tandem reaction sequences to access these molecules. The molecules and their syntheses are amenable to the inclusion of structural modifications and libraries of structurally diverse analogues will therefore be made using parallel synthesis techniques. Natural and synthetic compounds will then be tested against a panel of human tumour cell lines allowing iterative redesign of analogues to be undertaken in order to hone the activity and pharmacokinetic profile of promising lead compounds.