Kombinatorische Synthese von amphiphilen Porphyrinoiden für die Photodynamische Tumortherapie (PDT)

Photodynamic therapy (PDT) is a promising new treatment of small and superficial tumors. This therapy is based on selective tumor accumulation of photosensitizers, which form in the presence of oxygen and upon irradiation with visible light singlet oxygen (1O2), which finally destroys tumor cells. The synthetic route begins with transformation of heme. Along few synthetic steps into a mixture of 3/8-formyl deuteroporphyrin IX dimethyl ester wich were separated by a new method. Conversion of the formyl functions of the porphyrin into vinyl groups was accomplished by Wittig reaction. The optimization of amphiphilic properties of sensitizers crucial for tumor enrichment was achieved by combinatorial synthesis of chlorin derivatives with lipophilic side chains of different length. For biological and medical studies chlorins with 7 or 15 carbon atom containing side chains and Pd-chlorins were synthesized. Pd-chlorins form singlet oxygen with quantum yield ca. 100%.