Polyether marine natural products, exemplified by brevetoxins, ciguatoxins, and maitotoxin, present formidable and challenging synthetic targets due to their structural complexity and exceptionally potent biological activities. In order to address the issue of their total syntheses, we have developed new synthetic methodologies and strategies for the construction of medium-sized ether rings and convergent assembly of polyether system. These include (i) a base-induced 7-endo selective cyclization of a hydroxy epoxide, (ii) convergent synthesis of the fused nine-membered ether ring system, featuring an intramolecular reaction of a γ-alkoxyallylsilane with an acetal group and an SmI₂-mediated intramolecular Reformatsky reaction, (iii) intramolecular radical cyclization to construct O-linked oxepane ring system, (iv) convergent assembly of polyether frameworks based on B-alkyl Suzuki coupling of cyclic ketene acetal triflates and phosphates, and (v) construction of cyclic ethers from lactones based on Pd (O) -catalyzed carbonylation. These new methodologies and strategies were successfully applied to the synthesis of selected fragments of ciguatoxins and gambierol.