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.