Rapid construction of polycyclic ether skeletons using two-directional olefinic ester cyclization; total synthesis of (-)-brevenal and efforts towards the synthesis of yessotoxin and adriatoxin

Marine polycyclic ether natural products have attracted considerable attention from the scientific community because of their unique structures and intriguing biological activities. Olefinic ester cyclization is a highly efficient way to synthesize cyclic enol ethers, which are versatile synthetic precursors to polycyclic ether natural products and analogues. Chapter 1 describes our approach for rapid construction of polycyclic ether skeletons using a two-directional olefinic ester cyclization strategy. (-)-Brevenal is a pentacyclic polycyclic ether natural product isolated from the marine dinoflagellate Karenia brevis. Brevenal has shown to antagonize the toxic effect of brevetoxins in vivo, and can be potentially used as a lead compound for therapeutic treatment of mucociliary dysfunction. Chapter 2 describes our total synthesis of brevenal using a convergent and flexible esterification/olefinic ester cyclization strategy. Yessotoxins are a class of marine polycyclic ether natural products isolated from dinoflagellate and/or shellfish. Although over 40 of yessotoxins have been identified and characterized, their biological properties are still not clear due to very limited availabilities from natural source. Chapter 3 describes our efforts towards the synthesis of yessotoxin and one of its analogues, adriatoxin. The A-F and F-I ring systems of yessotoxin and adriatoxin were successfully synthesized utilizing both our iterative cyclic enol ether/C-glycoside formation and convergent esterification/olefinic ester cyclization strategies.