Discovery and synthesis of (+)/(–)-muyoquinone A, a pair of rare cyclopropane bridge-containing pentacyclic benzoquinone dimers with cytotoxic activity

Abstract

(±)-Muyoquinone A (1a/1b), a pair of rare racemic cyclopropane bridge-containing pentacyclic benzoquinone dimers with a tricyclo[2.2.2.0^2,7]octane core, were isolated from the endophytic fungus Muyocopron laterale. The structure was unambiguously established by spectroscopic and single-crystal X-ray diffraction analysis. We identified a biomimetic total synthesis of muyoquinone A (1) in seven steps by taking advantage of an intermolecular Diels–Alder homodimerization/dehydrogenation/intramolecular Diels–Alder cycloaddition cascade. (±)-Muyoquinone A (1a/1b) exhibited a selective in vitro cytotoxic effect against several human cancer cell lines (IC₅₀ 3.06–8.29 μM). Meanwhile, the racemic mixture showed stronger cytotoxic activities than the corresponding enantiomers.