Semisynthesis of jerantinine alkaloids

This thesis details the synthetic studies undertaken on natural products with anti-cancer activity. The general aim was to explore the synthesis and find an efficient and effective method to generate compounds, which would be used to further examine novel biological action. The first half of this thesis details the synthetic studies on the jerantinine family of natural products. The approach utilised the complex alkaloid (-)-tabersonine as a starting material, which was isolated from an abundant and sustainable source. Ultimately the first synthesis of (-)-jerantinine A and first enantioselective synthesis of (-)-jerantinine E were achieved. The biological activity of the synthetic material proved to be identical to that isolated from natural sources. The final part of this work describes the synthesis of a series of compounds derived from piperlongumine, which is of the Piperaceae family of natural products. The synthesis was accomplished using a novel methodology, which enabled the generation of a focussed library of derivatives. The compounds were tested by collaborators and their anti-cancer activity assessed in a variety of cell lines, revealing features of the structure activity relationship