Synthesis of fluorinated analogs of natural porphyrins potentially useful for the diagnosis and therapy of cancer

We have synthesized a number of fluorinated analogs of naturally important porphyrin derivatives, such as protoporphyrin and hematoporphyrin, which would be useful for the diagnosis and therapy of cancer, starting from deuteroporphyrin or using ring-closure methodology. Fluorovinyl derivatives of protoporphyrin were synthesized using the Wittig reaction or by employing organozinc reagents. The introduction of trifluorohydroxyethyl groups into deuteroporphyrin gave fluorinated analogs of hematoporphyrin, some of which were resolved to chiral isomers. Ring-closure of pyrrole derivatives carrying trifluorohydroxyethyl groups gave much better yields of chiral fluorinated analogs of hematoporphyrin than the resolution method. This review presents our syntheses of these fluorinated analogs and provides information on localizations of these porphyrins in some tumor cells and tissues.