Natural tanshinone-like heterocyclic-fused ortho-quinones from regioselective Diels–Alder reaction: Synthesis and cytotoxicity evaluation

Abstract

A series of new natural tanshinone-like oxoheterocyclic-fused ortho-quinone derivatives were synthesized from readily available benzofuranol and N-substituted dienes via IBX oxidation–cycloaddition–aromatization procedure. The regiospecific Diels–Alder cycloaddition reactions of N-dienes were achieved efficiently with a variety of dienophiles. It is found that the amide moiety in the molecular could be preserved or eliminated by control of the aromatization conditions. Selected oxoheterocyclic-fused ortho-quinones as well as several thioheterocyclic-fused ortho-quinones we obtained before were evaluated for their cytotoxicities on different cancer cell lines and the Structure–Activity Relationship (SAR) was discussed.