Synthetic studies towards the marine natural product phorboxazole A
The thesis describes synthetic studies towards the marine natural product phorboxazole A. This unprecedented compound was recently isolated from an Indian Ocean sponge and displays extraordinary levels of cytostatic activity against a broad range of human cancer cell lines. The Introduction summarises a variety of different natural products which have been targeted as anti-cancer agents, and compares their mode of action with that of phorboxazole A. A review of structurally related natural products is then included, followed by an account of how phorboxazole A was isolated and its structure determined. The Introduction concludes with a brief discussion on our planned retrosynthetic analysis and contemporaneous studies within our research group towards phorboxazole A. The Results and Discussion section of the thesis contains details of our synthetic studies towards two of the key fragments present from our retrosynthetic analysis, namely the oxazole bis-pyran unit and the side chain. A detailed discussion is presented throughout this section including a review of the hetero Diels-Alder reaction and methods of oxazole formation. This section culminates with a successful synthesis of the entire side chain of phorboxazole A. The third chapter of the thesis is the Experimental section containing full details of the preparative work completed and listing spectroscopic and analytical data for all new compounds synthesised during the study. The thesis is concluded by a schematic account of the contemporaneous total synthesis of phorboxazole A by the Forsyth research group at the University of Minnesota.