Highly Conjugated Norditerpenoid and Pyrroloquinoline Alkaloids with Potent PTP1B Inhibitory Activity from <i>Nigella glandulifera</i>

Three norditerpenoid alkaloids, nigelladines A–C (<b>1</b>–<b>3</b>), and one pyrroloquinoline alkaloid, nigellaquinomine (<b>4</b>), all possessing new skeletons with highly conjugated systems, were isolated from <i>Nigella glandulifera</i>. The 8a<i>S</i>-configuration for <b>1</b> and <b>2</b> was determined by comparison of the experimental and calculated electronic circular dichroism spectra. These alkaloids exhibited potent protein tyrosine phosphatase 1B (PTP1B) inhibitory activity but are devoid of cytotoxicity against the A431 cell line at 100 μM

Piperidine Alkaloids with Diverse Skeletons from <i>Anacyclus pyrethrum</i>

Fifteen new piperidine derivatives, pyracyclumines A–J (<b>1</b>–<b>10</b>), including five pairs of enantiomers, (+)-<b>1</b>/(−)-<b>1</b> to (+)-<b>5</b>/(−)-<b>5</b>, together with three known compounds, agrocybenine (<b>11</b>), 4,6,6-trimethyl-5,6-dihydro-2­(1<i>H</i>)-pyridone (<b>12</b>), and 3,5,5-trimethyl-1,5-dihydro-2<i>H</i>-pyrrol-2-one (<b>13</b>), were isolated from the roots of <i>Anacyclus pyrethrum</i>. Pyracyclumines A, B, and H (<b>1</b>, <b>2</b>, and <b>8</b>) 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 (<b>3</b>) 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 (<b>1</b>–<b>5</b>) were further separated by chiral HPLC to give the enantiomers (+)-<b>1</b>/(−)-<b>1</b> to (+)-<b>5</b>/(−)-<b>5</b>, 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 <b>12</b> and <b>13</b>. All of the isolated compounds were tested for their inhibitory effects on menin–mixed lineage leukemia 1 protein–protein interaction