Chapter 8 Total synthesis of myriaporones 1, 3, and 4

Publisher Summary The work in the total synthesis of myriaporones 1, 3, and 4was initiated by interest in the complex marine polyketide, Tedanolide. Tedanolide is a potent cytotoxic macrolide isolated from the Caribbean sponge, Tedania ignis . Tedanolide demonstrated cytotoxicity against cancer cell lines, but detailed biological studies were hampered by material supply issues. Despite significant synthetic interest, only 13-desoxytedanolide has been prepared to date. The structural similarities between the myriaporones and tedanolide suggest an evolutionary relationship among the organisms (PKS genes) that produce such elegant chemical entities. Moreover, it was wondered if their biological activity could be related as well and whether synthetic work toward the simpler of the two, the myriaporones, might lead to an understanding of both and an opportunity for new leads in cancer chemotherapy. The primary goal has been designing and executing efficient and elegant total syntheses of these natural products. To this end, obvious synthetic challenges have been identified and solutions have been proposed that offered high probabilities for success. Where possible, the aim has been to incorporate strategies applicable to the overall goals of the program and tactics that would highlight recent advances in chemical synthesis.