The primary focus of this investigation is the development of methodology that will lead to an enantioselective total synthesis of diazonamide A. Particular attention will be given to synthesizing the quaternary center in the molecule. An epoxy alcohol-aldol rearrangement will be explored as a means to synthesize this challenging protein of the molecule in a catalytic asymmetric fashion. Additionally, unique syntheses of both oxazoles have been proposed in order to efficiently assemble the directly linked, fully substituted bisoxazole subunit. Finally, a convergent and versatile strategy for the use of this methodology in a total synthesis has been designed. Diazonamide A is of particular interest because of the extremely low IC50 values reported against HCT-116 human colon carcinoma and B-16 murine melanoma cancer cell lines in vitro. The diazonamides were isolated from the ascidian Diazona chinensis in 1990. Many biologically and structurally interesting compounds have been obtained from ascidians in recent years. The diazonamides are also related structurally to a number of natural products from different sources which also have promising biological relevance.
