Rearranged Homoadamantane-Type Polycyclic Polyprenylated Acylphloroglucinols from Hypericum pseudohenryi

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Organic Chemistry

Background:

• *Hypericum pseudohenryi* is a plant source of bioactive compounds.
• Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of natural products with diverse biological activities.
• Rearranged homoadamantane structures are rare in natural products.

Purpose of the Study:

• To isolate and characterize new compounds from *Hypericum pseudohenryi*.
• To elucidate the structures of novel rearranged homoadamantane-type PPAPs.
• To evaluate the acetylcholinesterase (AChE) inhibitory activity of the isolated compounds.

Main Methods:

• Isolation and purification using chromatographic techniques.
• Structure elucidation via spectroscopic analysis (NMR, MS) and X-ray crystallography.
• Quantum-chemical calculations for structural confirmation.
• Acetylcholinesterase (AChE) inhibition assays.
• Molecular docking studies to investigate compound-enzyme interactions.

Main Results:

• Three novel compounds, Hypseudohenones A-C (1-3), were isolated and characterized.
• The compounds possess a unique tricyclo[4.3.1.1^3,8]undecane-2,4,10-trione core, representing the first reported rearranged homoadamantane-type PPAPs.
• A reliable method for determining relative configuration at C-3 was established.
• Compounds 2 and 3 demonstrated significant AChE inhibitory activity.
• Molecular docking provided insights into the binding modes of compounds 2-3 with AChE.

Conclusions:

• Hypseudohenones A-C are novel natural products with unprecedented structural features.
• The isolated compounds, particularly 2 and 3, are potent inhibitors of AChE.
• These findings highlight the potential of *Hypericum pseudohenryi* as a source of new therapeutic agents for neurodegenerative diseases.