Fig. 2

Strategies for the construction of tetracyclic meroterpenoids. a The polyene cyclization reaction of aryl enol ether 7 enabled rapid assembly of the trans-decalin substructure of 5-epi-aureol (9) and cyclosmensopongine (5). However, this strategy could not be adapted for the preparation of meroterpenoids containing a cis-decalin subunit. b Synthesis of the 5,6-dehydrodecalin intermediate III should be accomplished by a highly modular, three-component coupling strategy of phenol IV, diene V, and dienophile VI. The ability to construct both cis- and trans-decalins from a common precursor would allow for the synthesis of 1–6 and a variety of non-natural derivatives for biological screening. Color coding: blue, cis-decalin, green, trans-decalin. R¹ = alkyl, R² = H or OBn, X_c = chiral auxiliary