OPTIMIZATION OF THE FIRST COUPLING IN PHIDIANADINE FURAN ANALOG SYNTHESIS

Two compounds, phidianadine A and B, were recently found in the marine mollusk Phidiana militaris. These compounds have three key areas: indole, 1,2,4-oxadiazole, and the side chain. Analogues of these molecules that replace the alkyl side chain with a biaryl side chain have shown to protect nerve cells from oxidative damage. This type of damage has been correlated to the onset and progression of neurodegenerative diseases such as Alzheimer\u27s. The goal of this project is to develop new a synthetic approach to these phidianidine analogues that allows for the indole region to be easily modified. This process installs the side chain first followed by addition of the desired indole to complete the analog. The current approach relies on multiple Pd crosscoupling reactions which required optimization. The initial Suzuki reaction in the sequence was examined to determine the effect of changing the coupling partner, catalyst and other reaction conditions