Solid-Phase Synthesis for the Construction of Biologically Interesting Molecules and the Total Synthesis of Trioxacarcin DC-45-A2

This thesis covers three research projects in addition to a literature survey on solid-phase organic synthesis and photolabile linkers. Synthesis of Doxorubicin Derivatives on Photolabile Solid Support. The synthesis of doxorubicin derivatives on photolabile solid support, compatible with bead-based screening, was investigated. Two different strategies for the synthesis of doxorubicin derivatives were developed leading to the synthesis of doxorubicin derivatives with both amino acids and peptide fragments attached in good to excellent crude purities. Total Synthesis of Trioxacarcin DC-45-A2. In efforts towards the total synthesis of trioxacarcin DC-45-A2 by the Nicolaou group anew and efficient route for a key fragment was optimized. The new route featured distinct and high yielding steps and thus provided superior access to this key building block in terms of overall yield, step count and scalability. Furthermore a route to another key building block was developed featuring a Stille cross-coupling.Synthesis of Poly-fused Heterocycles. In the search for new biologically active compounds a methodology for the synthesis of polyfused heterocycles was investigated. This led to the development and optimization of a key aldol condensation/conjugate addition sequence for the synthesis of poly-fused heterocycles.