Enantioselective synthesis of (-)-exiguolide by iterative stereoselective dioxinone-directed Prins cyclizations.

Exiguolide (1, Scheme 1) is an unusual natural product isolated in 2006 by Ohta, Ikegami, and co-workers from the marine sponge Geodia exigua Thiele.[1] This molecule inhibits the fertilization of sea urchin gametes (H. pulcherrimus) at a concentration of 20 μm but does not affect the development of the already fertilized eggs at higher concentrations (100 μm), thus indicating that it might possess relevant anticancer activity.[2] The similarity of compound 1 to the bryostatin family of natural products, which are known antitumor compounds, was proposed by Cossy[3] and also intrigued us. In particular, the bispyran architecture and the exocyclic enoate appended onto a tetrahydropyran ring are motifs common to both exiguolide and the bryostatins.[4]