| Part 1. A new method for the rapid preparation of the commercially important meso substituted aryl porphyrins, such as 5,10,15,20-tetraphenylporphyrin (TPP), is presented. This one-step solvent free method involves heating the aromatic aldehyde to ∼200°*C in a vial fitted with a septum cap, followed by addition of the pyrrole and maintaining the temperature for another 20 minutes. The dioxygen in air serves as the oxidant, and the addition of benzoic acid as a catalyst improves the yields of TPP and many other porphyrins to 5–32%. Herein is also presented an examination of the many factors that influence the yield, the ease of purification, and the ability to scale-up the reaction. Since the tarry bi-products from this method are much less soluble than in most other synthetic strategies, much less solvent is required for purification. Thus, this method provides an attractive alternative to others because of its minimal waste generation in terms of both solvent and chromatography support.; Part 2. The synthesis and characterization of combinatorial libraries of meso-tetraphenylporphyrin (TPP) derivatives—core structured libraries—is reported. The libraries are readily further derivatized to create libraries of amphipathic porphyrins. These amphipathic porphyrins are then screened for DNA binding, isolated, and examined for their ability to cleave plasmid DNA. Several novel porphyrins are identified and indicate multifunctional, amphipathic porphyrins bind more strongly than heretofore known homosubsituted porphyrins, thus may be lead compounds for photodynamic therapeutics.; Part 3. A method for the synthesis of porphyrins on a solid support was developed. Using a non-swollen Wang resin, the major product (>90%) is the trans substituted ABAB pattern porphyrin. The yield is 4.5% based on the loading of the aldehyde, which is 10mg porphyrin/g resin. When the resin was pre-swollen and a second aldehyde was used, a mixture of porphyrins was resulted. This may arise from the density of active sites on the Wang resin. Thus, at this point in the development process, this is not an attractive route to porphyrin libraries on solid support, but is an unusual alternative to the multi-step procedures to make trans substituted porphyrins.; Part 4. A tetra-Grignard reagent zinc-5,10,15,20-Tetrakis-(4-bromomagnesiumphenyl)porphyrin was likely synthesized with a yield of ∼33%. This poly-Grignard reagent was used as an attempt to synthesize a porphyrin cube. A interesting porphyrin 5,10,15,20-Tetrakis-(4-diphenylmethanolphenyl)porphyrin, which has 4 triphenyl carbonals was synthesized with a yield of ∼37%. This latter compound was made by reaction of excess phenyl Grignard with 5,10,15,20-Tetrakis-(4-methoxycarbonylphenyl)porphyrin. |
