Pseudoheterines A–I, Polyheterocyclic Alkaloids from <i>Pseudostellaria heterophylla</i> with Neuroprotective Activities

Nine undescribed polyheterocyclic pyrrole alkaloids, pseudoheterines A-I (<b>1</b>-<b>7</b>, <b>11</b>, and <b>12</b>), along with four known analogues (<b>8</b>-<b>10</b> and <b>13</b>), were isolated from the plant <i>Pseudostellaria heterophylla</i>. The structures and absolute configurations of compounds <b>1</b>-<b>7</b>, <b>11</b>, and <b>12</b> were determined by extensive spectroscopic analysis, ECD calculations, and X-ray diffraction. Compounds <b>1</b>-<b>6</b> are six unprecedented tetracyclic alkaloids with a triheterocyclic moiety, pyrrole-dihydrofuran-pyrrolidone core. Compounds <b>1</b>, <b>3</b>, and <b>5</b> present a fourth aromatic heterocyclic ring D, while <b>2</b>, <b>4</b>, and <b>6</b> possess an aromatic ring attached by an ester linkage. Compounds <b>6</b> and <b>9</b> exhibited neuroprotective activities by inhibiting apoptosis in CdCl₂-induced PC-12 cells, and ameliorated CdCl₂-induced neural damage in zebrafish.