Development of Efficient Methods for the Synthesis of Polycyclic Ethers

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Since the first isolation of brevetoxin B, a neurotoxin produced by the red tide organism Gymnodinium breve, many marine polycyclic ethers of this type have been reported. The most characteristic structural feature of these natural products is trans-fused polycyclic ether ring system. The synthetically challenging unique structures and their potent biological activities have attracted the attention of numerous synthetic organic chemists.In this project, we have developed an extremely facile and highly efficient strategy for the iterative synthesis of a trans-fused polytetrahydropyran ring system based on the SmI_2-induced reductive intramolecular cyclization. This method is also effective for the synthesis of polycyclic ether ring systems including oxepane and also an angular methyl group. Based on the present SmI_2-induced cyclization, a strategy for two directional synthesis of polycyclic ether was developed.A very efficient convergent strategy for the construction of the trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed based on the acetylide-triflate coupling of two tetrahydropyrans, oxidation of the alkyne group to an a-diketone, double cyclization to 6,6,6,6-membered tetracyclic diacetal, and stereoselective reduction of the diacetal with Et_3SiH-TMSOTf.In conclusion, we have developed very simple and efficient strategies for the construction of trans-fused polycyclic cyclic ether ring system. This strategy would be widely applicable to efficient syntheses of natural polycyclic ethers