Synthesis of Phenanthridine-Containing Polycyclic Ring Systems through Intramolecular Diels-Alder Reaction on Furan (IMDAF)

Abstract

The work described in this thesis focused on developing a method to synthesise a variety of organic molecules with imidazophenanthridine or pyrrolophenanthridine ring structures. These are complex structures with previously reported activities against certain cancer cell lines, and as acetylcholinesterase inhibitors, among else. Acetylcholinesterase inhibitors are potentially useful as drugs for the treatment of Alzheimer’s disease. This newly developed route to imidazophenanthridines allow for a substitution pattern not previously reported for similar structures, namely the inclusion of electron-withdrawing groups in the phenanthridine A-ring. These types of imidazophenanthridines are relatively unexplored territory, so the synthesis route’s potential to produce a variety of different substitution patterns is important. Some of the products that were tested for biological activities displayed significant activity against certain protozoa parasites responsible for tropical diseases. In the method developed towards pyrrolophenanthridines, an elegant solution was found to introduce one of the two characteristic hydroxyl groups observed in naturally occurring analogs. It was also discovered that some of the synthesised compounds were sensitive towards oxidation, which can be exploited in further studies to introduce additional functionality.