gymnocin-a and gambierol

Marine polycyclic ether natural products continue to fascinate chemists and biologists due to their exceptionally large and complex molecular architectures and potent and diverse biological activities. Tremendous progress has been made over the past decade toward the total synthesis of marine polycyclic ether natural products. In this area, a convergent strategy for assembling small fragments into an entire molecule always plays a key role in successful total synthesis. This review describes our efforts to develop convergent strategies for the synthesis of polycyclic ethers and their application to the total synthesis of gambierol, gymnocin-A, and brevenal, and to the partial synthesis of the central part of ciguatoxins and the nonacyclic polyether skeleton of gambieric acids.

Topics: Ciguatoxins; Ethers, Cyclic; Marine Biology; Molecular Structure; Polycyclic Compounds; Thiopental

The combination of a trimethylsilyl group, a Brønsted base, a fluoride source, and a hydroxylic solvent enables the first construction of the tetrad of tetrahydropyran rings found in the majority of the ladder polyether natural products by way of a cascade of epoxide-opening events that emulates the final step of Nakanishi's proposed biosynthetic pathway. The trimethylsilyl group disappears during the course of the cascade, and thus these are the first epoxide ring-opening cascades that afford ladder polyether subunits containing no directing groups at the end of the cascade.

Topics: Ciguatoxins; Epoxy Compounds; Ethers, Cyclic; Furans; Molecular Conformation; Mollusk Venoms; Oxocins; Polycyclic Compounds; Polymers