The α-pyrone natural products pyrophen and campyrones A–C, originally isolated from the fungus <i>Aspergillus niger</i>, exhibit promising antimicrobial and cytotoxic activity. Herein we describe the first total syntheses of these compounds starting from commercially available amino acid derivatives. Key steps in this route include a vinylogous Claisen condensation with an acylbenzotriazole and subsequent formation of the characteristic α-pyrone ring via a dioxinone thermolysis / cyclization cascade. This scalable six-step route affords the natural products in 15-25% overall yield, allowing for the preparation of sufficient quantities of these compounds and their analogs for further testing in biological assays. Synthetic efforts towards several structurally related natural products, including aspernigin B and a naphthoquinone adduct of pyrophen, are also described.

Total synthesis of pyrophen and campyrones A-C

255th National Meeting (2018)

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