Hannah Yu: Biomimetic Synthesis Towards (±)-Hypeisoxazole A Under Biogenic Conditions

<p dir="ltr">(±)-Hypeisoxazole A, a novel spiro-benzylisoquinoline-derived alkaloid, was isolated from the medicinal herb Hypecoum erectum as a racemic pair in 2022.1 Hypecoum erectum is a winter annual herb widely distributed in China that has been traditionally used in folk medicine for its antipyretic, analgesic and anti-inflammatory effects, particularly in the treatment of fever, pharyngitis and pain-related conditions.1 (±)-Hypeisoxazole A has a complicated hexacyclic system consisting of two indeno rings that are connected via an isoxazolidine ring. This rare angularly fused triquinane-type scaffold contains a highly strained 5/5/5 fused ring system. The aim of the project is to synthesise (±)-hypeisoxazole A, by using a biomimetic strategy with a particular focus on the key intramolecular 1,3-dipolar cycloaddition under biogenic conditions, such as water, buffer and surfactant. A model study was conducted to explore the transformation from hydroxylamine to the core 5/5/5 fused ring structure via the formation of the key intermediate nitrone.</p>