Azaphilones are a class of fungal natural products that contain a highly oxygenated pyranoquinone bicyclic core. Many of these fungal pigments possess potent biologically activity (exhibiting anticancer, anti-inflammatory, and antimicrobial properties), making them interesting synthetic targets for the development of new pharmaceutical agents. However, their construction has proven challenging due to their nonaromatic, bicyclic structure and the presence of a stereocenter. Nature has evolved efficient biocatalysts to perform oxidative dearomatization with exquisite site- and stereoselectivity, making them an exciting alternative to the current state of the art synthetic methods. These enzymes can operate on a number of substrates under mild conditions, using O<sub>2</sub> as the stoichiometric oxidant. Therefore, this work seeks to develop a chemoenzymatic, stereodivergent route to azaphilone natural products through the use of these biocatalysts. Thus far, progress has been made towards these compounds by the production of a common substrate that can be dearomatized by two homologous flavin-dependent monooxygenases, giving each C3-epimer of the general azaphilone scaffold.

Chemoenzymatic, stereodivergent total synthesis of azaphilone natural products

256th National Meeting (2018)

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