Synthetic Studies Toward Rubioncolin B

Herein, we report our synthetic studies toward rubioncolin B ( 1 ), a heptacyclic naphthohydroquinone dimer with antitumor activity. Our strategy is based on the intermolecular [4 + 2]‐cycloaddition reaction between an ortho ‐naphthoquinone methide ( o ‐NQM), which is generated in situ from a 1‐naphthol derivative under catalytic Lewis acid conditions, and a naphthofuran derivative, thereby enabling the construction of a hexacyclic compound. We then explored three synthetic approaches for appending the remaining ring structure to the hexacyclic compound. Among them, the sequence involving the introduction of a Wittig reagent and subsequent cyclization proved effective, furnishing a cyclic acetal with the same ring structure as 1 . This strategy not only demonstrates that accessing the highly congested architecture of 1 is feasible but also provides a versatile platform for the synthesis of structurally diverse analogs, thereby facilitating subsequent biological investigations, including structure–activity relationship studies.