Bromotyrosine-derived natural products: synthetic and biological studies

Abstract

Bromotyrosine-derived natural products are a fascinating class of compounds that are produced by marine sponges of the order Verongida. Furthermore, they exhibit a rich variety of chemical structures and display a diverse range of bioactivities which makes them of great interest to both the chemical and biological research communities. This thesis is divided into four Chapters and describes the total syntheses of five bromotyrosine-derived natural products and analogues thereof. The anticancer activity of these compounds was also investigated. In addition, studies towards the total syntheses of the ceratamines are reported. The first Chapter gives a general introduction into the history, biosynthesis, structures and biological activities of bromotyrosine-derived natural products. A background into the anticancer properties of ceratamines A and B is also provided. The research in Chapter two is concerned with bromotyrosine-derived oximes and is divided into two parts. The syntheses of the natural products (5)-bromoverongamine, ianthelline and JBIR-44 are described in Part one and the structure-activity relationship studies into these products is described in Part two. The total syntheses of subereamollines A and B are discussed in Chapter three. Furthermore, both enantiomers of the natural products were accessed and their absolute stereochemistry was unambiguously assigned. The first section of Chapter four provides an in-depth review of the research carried out by the Andersen and Coleman groups into the ceratamines. This is followed by an account of the Ley group approach towards the syntheses of these natural products.