This account describes the convergent synthesis of (−)-okilactomycin. The first-generation approach focused on the assembly of two complex fragments through a Prins reaction of a dioxinone and α-hydroxy aldehyde. While this route was not ultimately successful, a related Maitland–Japp process employing a β-keto ester in place of the dioxinone fragment provided the necessary union of functionalized intermediate, thereby establishing the full carbon framework of the natural product. The synthesis also employed a highly diastereoselective Lewis acid-promoted Diels–Alder reaction and an olefin ring-closing metathesis to close the strained 11-membered macrocycle of the natural product.