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.