Pseudoheterines A–I, Polyheterocyclic Alkaloids from Pseudostellaria heterophylla with Neuroprotective Activities

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