Abstract

Combretastatin A-4, a naturally occurring compound isolated from the South African bush willow Combretum Caf rum, has derivatives such as chalcones. These compounds contain antibacterial, anti mitotic, anticancer, and antibiotic properties. For the purposes of this research, the chalcones are the basis for the synthesis of pyrroles. Lamellarin pyrroles have been synthesized from chalcones using electron cyclization chemistry of chalcones with glycine ethyl esters. The focus here is to generate pyrroles from chalcones en route to ynedienes. Ynedienes can be generated by the coupling of a halopyrrole with a terminal alkyne. These ynedienes will be examined for their ability to induce DNA cleavage via diradicals following the ynediene electrocyclization. The synthesis and purification of an O-protected hydroxyl chalcone has proven to be challenging. The scope of chalcones that can be utilized in the electrocyclization process has been expanded and will be discussed. The use of N-iodosuccinimide in the reaction process provides a halo-substituted pyrrole that will be coupled with terminal alkynes. The alkyne provides a handle for versatility in the next step(s) of the synthetic route. In-silico docking, as shown below in Figure 1, has helped form hypotheses for the results of future in-vitro testing of these analogs once they are available.

How to Cite