Enantioselective Synthesis of (−)‐Exiguolide by Iterative Stereoselective Dioxinone‐Directed Prins Cyclizations

Three become one: The title compound can be prepared in 26 steps by employing a unified Prins cyclization strategy to construct both tetrahydropyran rings (see scheme). The route combines two similar dioxinone fragments and one aldehyde component to generate the core structure. (−)-Exiguolide selectively inhibits the growth of A549 cancer cells at low concentrations; the triene side chain and the Z-enoate geometry are both necessary for this cytotoxicity.