3,5-Dimethylorsellinic Acid (DMOA)-Derived Meroterpenoid Ortholactones (−)-Novofumigatonin, (−)-Asnovolin F, and (−)-Asnovolin G: Total Syntheses and Related Studies

We disclose a full account of the total synthesis of (-)-novofumigatonin and the first syntheses of (-)-asnovolin F and (-)-asnovolin G. The overarching approach to these 3,5-dimethylorsellinic acid (DMOA)-derived spiromeroterpenoid ortholactones relies on two central features: highly convergent coupling of fragments of roughly equal complexity and subsequent formation of the embedded ortholactone cages. The scope of coupling by 1,2-addition of a hindered, neopentylic organolithium with a collection of highly congested tetrasubstituted cyclohexanones, integral to concise assembly of the stereochemically dense carbon skeleton, is described. The study of ortholactone formation provides insights into synthetic pathways to the embedded dioxabicyclo[3.2.1]octane. An advanced intermediate featuring the ortholactone-acetal core enables access to all three spiromeroterpenoid natural products.