Total synthesis of new photosensitizers like benzopophyrins with potential activities in photodynamic therapy

Abstract

In this project we propose the total synthesis of new benzoporphyrin derivatives. The key objective of the project is to contribute to methodological and synthetic development inside the chemistry of heterocyclic compounds, and explore structures with appropriate features to be used in Photodynamic Therapy (PDT).In the first synthetic approach, we propose the synthesis of some tetrapyrimidinoporphyrin derivatives, starting from the synthesis of strategically functionalized pyrroles for synthetic and PDT studies.In the second approach, we intend to invest efforts on the synthesis of some substituted pyrroles, all converging for the synthesis of tetrapyridoporphyrins. In this part of the proposal, we suggested alternative pathways for pyrroles and porphyrin intermediates synthesis, which represent important synthetic challenges and are also interesting to photophysical and photobiological studies.The third proposal of this project is a synthetic alternative approach to the previous strategies and represent, in some aspects, an application of some results obtained by the candidate in previous studies. The latter approach is focused on the synthesis of benzoporphyrin derivatives fused with a variety of imide and pharmacophoric groups. Besides the synthesis, chemical, physical and preliminary photophysical (on photodynamic activity) characterization will be performed. The synthetic results which will be obtained in this project must represent remarkable importance; they justify this research from the perspective of developing methodologies and synthesis of new benzoporphyrin core structures. Moreover, if identified as good candidates for PDT studies, the compounds should be further evaluated in conjunction with groups in the PDT area, which collaborate with our newly established research group at the chemistry department of UFSCar.