Bromotyrosine-derived natural products: synthetic and biological studies

摘要

Bromotyrosine-derived natural products are a fascinating class of compounds that areproduced by marine sponges of the order Verongida. Furthermore, they exhibit a richvariety of chemical structures and display a diverse range of bioactivities whichmakes them of great interest to both the chemical and biological researchcommunities.This thesis is divided into four Chapters and describes the total syntheses of fivebromotyrosine-derived natural products and analogues thereof. The anticancer activityof these compounds was also investigated. In addition, studies towards the totalsyntheses of the ceratamines are reported.The first Chapter gives a general introduction into the history, biosynthesis, structuresand biological activities of bromotyrosine-derived natural products. A backgroundinto the anticancer properties of ceratamines A and B is also provided.The research in Chapter two is concerned with bromotyrosine-derived oximes and isdivided into two parts. The syntheses of the natural products (5)-bromoverongamine,ianthelline and JBIR-44 are described in Part one and the structure-activityrelationship 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 theirabsolute stereochemistry was unambiguously assigned.The first section of Chapter four provides an in-depth review of the research carriedout by the Andersen and Coleman groups into the ceratamines. This is followed by anaccount of the Ley group approach towards the syntheses of these natural products.