1) Synthetic Studies Toward Rubioncolin B
Takaaki Aijima, Shuji Akai, Yoshinari Sawama
Eur. J. Org. Chem. 2026, 29, e202501103.
DOI: 10.1002/ejoc.202501103
Abstract: 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.