Synthetic and mechanistic studies of polyazole Cyclopeptide natural products : Aurantizolicin and Urukthapelstatin A This PhD thesis describes the development of an effective total synthesis of the strongly cytotoxic polyazole cyclopeptide natural product aurantizolicin. The synthesis design combined building block synthesis in solution with solid phase peptide synthesis to enable the rapid diversification of the natural product. Macrothiolactonization and aza Wittig chemistry allowed the formation of the macrocyclically embedded thiazole. Thereby the stereochemical assignment of the natural product and the formation of an extensive library of analogs have been achieved. Profiling the analog library for its growth inhibitory effect on human cancer cells revealed crucial structural features and significantly expanded the knowledge of the structure–activity relationships (SAR) of this natural product class. Based on the SAR chemical probes have been designed and synthesized to enable further investigations towards the elucidation of the mechanism of action of aurantizolicin. These probes included cyclopeptide–dye conjugates compounds for photoaffinity labeling and immobilized cyclopeptides. Initial investigations utilizing the immobilized cyclopeptides in compound centric chemical proteomics experiments suggested an RNA associated mechanism of action. Beyond natural product chemistry 5 sulfamoyloxy oxazoles have been developed as competent C–O electrophiles for Suzuki–Miyaura cross coupling reactions as well as for aromatic nucleophilic substitutions conjugate additions of various heteroatom nucleophiles. The reactivity of peptide integrated oxazolyl sulfamates has been profiled to allow the divergent synthesis of oxazolyl arenes 5 amino oxazoles oxazolyl sulfides and oxazolyl aryl ethers. The relevance of the organic synthesis method has been demonstrated by the total synthesis of the natural product almazole D.