Synthesis of Phidianidines A and B

Phidianidines A and B are compounds originally isolated from the shell-less sea mollusk, Phidiana militaris, in 2011. Testing of phidianidines A and B revealed significant cytotoxicity against C6 rat glioma cells, 3T3-L1 murine embryonic fibroblasts and HeLa human epithelial cervical cancer cells. The phidianidines are unique because they are the first natural products discovered with a 1,2,4-Oxadiazole ring system. Many other man-made medicinal drugs have a 1,2,4- or 1,3,4-Oxadiazole ring. Therefore, there is the possibility for derivatives of phidianidines to be more potent. Total synthesis of phidianidines A and B has been published, but with low yields and an unstable starting material. It is our intent to provide a more concise synthesis of phidianidines A and B using stable starting materials and improve the overall yield of the synthesis. Our convergent approach will start from 1,5-pentadiamine and 6-bromoindole that will be used to create the two precursors that will be combined near the end of the synthesis. This would make our method a more appealing synthesis route for further study and for effective synthesis in industry