Diversification of ( E,E )-1,6-Dioxo-2,4-Dienes for the Synthesis of (+)-Aspicillin, Isolaurepan, and β-Parinaric Acid.

A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product β-parinaric acid and the total synthesis of non-terpenoid metabolite isolaurepan have been achieved using a ruthenium-catalyzed stereo- and chemoselective oxidative coupling reaction of easily accessible vinyl ketones and acrylates. The crucial transformation involves the efficient synthesis and functionalization of stereodefined ( E,E )-1,6-dioxo-2,4-dienes using simple reaction protocols, which enabled straightforward access to a diverse range of bioactive natural products.