Auranthine, a Benzodiazepinone from Penicillium aurantiogriseum: Refined Structure, Absolute Configuration, and Cytotoxicity

The structure of the known Penicillium aurantiogriseum-derived secondary metabolite auranthine was refined using a combination of synthetic, spectroscopic, and X-ray diffractometric approaches. Thus, auranthine was shown to be a fused quinazolino benzodiazepinedione (2) bearing an acyclic aliphatic nitrile moiety, thereby significantly differing from the originally proposed structure 1 published in 1986. Its absolute configuration was confirmed by CD spectroscopy and DFT calculations. The cultivation of P. aurantiogriseum was optimized, allowing high production of auranthine. The cytotoxicity profile of auranthine and its semisynthetic analogues is reported. The refined structure of auranthine provides a valid target for the total synthesis of this underexplored natural product and its derivatives.