Piperidine Alkaloids with Diverse Skeletons from Anacyclus pyrethrum

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Organic Chemistry

Background:

• Anacyclus pyrethrum is a plant known for its medicinal properties.
• Piperidine alkaloids represent a diverse class of natural products with significant biological activities.
• The exploration of plant-derived compounds is crucial for discovering novel therapeutic agents.

Purpose of the Study:

• To isolate and characterize new piperidine derivatives from Anacyclus pyrethrum roots.
• To elucidate the structures of novel dimeric and tricyclic piperidine skeletons.
• To investigate the inhibitory effects of these compounds on menin-mixed lineage leukemia 1 protein-protein interaction.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation through Nuclear Magnetic Resonance (NMR) and High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS).
• Separation of enantiomers using chiral High-Performance Liquid Chromatography (HPLC) and determination of absolute configurations via Electronic Circular Dichroism (ECD) spectroscopy.

Main Results:

• Fifteen new piperidine derivatives (pyracyclumines A-J) and three known compounds were isolated.
• Novel dimeric piperidine skeletons (6/5/6/6 and 6/5/6) and a 1,4,6-triazaindan skeleton were identified.
• The inhibitory effects of all isolated compounds on menin-mixed lineage leukemia 1 protein-protein interaction were evaluated.

Conclusions:

• The study successfully identified and characterized novel piperidine alkaloids from Anacyclus pyrethrum.
• The structural diversity includes unique dimeric and tricyclic frameworks, expanding the known chemical space of piperidine alkaloids.
• The isolated compounds provide a basis for further investigation into their potential as inhibitors of menin-mixed lineage leukemia 1 protein-protein interaction.