| dc.description.abstract | Phenanthridone alkaloids, many of which have been studied in vitro and in vivo, have been extracted from the bulbs and petals of Amaryllidaceae plants. Due to their specific tri- and tetracyclic skeletons, these alkaloids have been shown to possess antiviral, antimitotic, and anti- tumor qualities. The specific phenanthridone alkaloids Narciclasine, Lycoricidine and Pancratistatin have been shown to exhibit potent cytotoxic activity and to inhibit cell division in E. coli and sarcoma cells. Previous syntheses of phenanthridone alkaloids have focused on a retrosynthetic approach whereby a modified hexose sugar comprises the C-ring. This is added to a starting material containing the A-ring, and the last step in these syntheses uses an expensive metal to catalyze the formation of the B-ring. Our novel synthesis, however, begins with an aromatic dicarboxylic acid that contains the A-ring. Cyclization of this compound allows the B- ring to be formed early in the synthesis without the need of expensive metals. Carbon 4 on the B- ring is then available for functionalization. The C-ring results from a ring-closing metathesis reaction and subsequent ring expansion to give the phenanthridinone ring system. Current research on a model system has shown this route to be high-yielding. If an efficient method to synthesize the phenanthridinone ring system is developed, it will provide a template to produce numerous modified alkaloids in sizable quantities sufficient for pharmacological testing. | |
