Piperidine Alkaloids with Diverse Skeletons from Anacyclus pyrethrum

Fifteen new piperidine derivatives, pyracyclumines A–J (1–10), including five pairs of enantiomers, (+)-1/(−)-1 to (+)-5/(−)-5, together with three known compounds, agrocybenine (11), 4,6,6-trimethyl-5,6-dihydro-2­(1H)-pyridone (12), and 3,5,5-trimethyl-1,5-dihydro-2H-pyrrol-2-one (13), were isolated from the roots of Anacyclus pyrethrum. Pyracyclumines A, B, and H (1, 2, and 8) possess a novel 6/5/6/6 dimeric piperidine skeleton, a unique 6/5/6 dimeric piperidine skeleton, and a 1,4,6-triazaindan skeleton, respectively. Pyracyclumine C (3) is based on a rare cyclopentane–piperidine framework. The structures of the isolated compounds were established by analysis of their NMR and HRESIMS data. The racemic pyracyclumines A–E (1–5) were further separated by chiral HPLC to give the enantiomers (+)-1/(−)-1 to (+)-5/(−)-5, for which the absolute configurations were determined by comparison of their experimental and calculated ECD spectra. The plausible biogenetic pathways of these piperidine alkaloids were proposed starting from the basic units of compounds 12 and 13. All of the isolated compounds were tested for their inhibitory effects on menin–mixed lineage leukemia 1 protein–protein interaction.