Convergent Synthesis of Fused Ring Systems in Large Polycyclic Ethers

This article reviews our studies on the oxiranyl anion-based, [X+2+Y]-type convergent strategy for the synthesis of polycyclic ether natural products. The strategy is noteworthy for its flexibility, which allows for the generation of different-sized fused ring systems based on a ring expansion reaction. For a precise understanding of this key ring expansion, we first focused on the reaction mechanism, in which an equatorial attack of TMS-diazomethane was determined to be the crucial step. In the later part of this review, the application of our oxiranyl anion-based strategy to large fused ring systems is described. The advantageous flexibility is highlighted in the divergent synthesis of five octacyclic ethers involving the CDEFGHIJ-ring skeleton of yessotoxin and its ring-modified analogs. Total synthesis of gymnocin-A was achieved using the oxiranyl anion convergent strategy, which furnished its large system of fourteen contiguous ether rings.