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 CdCl 2 -induced PC-12 cells, and ameliorated CdCl 2 -induced neural damage in zebrafish.