Design and synthesis of a trans-fused polycyclic ether skeleton as an α-helix mimetic scaffold

Inspired by the common skeletal feature of potent marine toxins, a ladder-like polycyclic ether scaffold was designed as the basis for the synthesis of structurally defined α-helix mimics. A synthetic route to trans-fused 6/6/6/6/6 pentacyclic ether skeletons is presented, involving the iterative assembly of tetrahydropyran rings via the SmI2-mediated coupling reaction of α-sulfonyl ketones with aldehydes.