Hypoxia-Protective Azaphilone Adducts from Peyronellaea glomerata

Peyronellones A and B ( 1 and 2 ), a pair of rare tetracyclic caged adducts of azaphilone with pyruvic acid, along with four new analogues ( 3 – 6 ), were isolated from solid cultures of the endophytic fungus Peyronellaea glomerata . Their structures were elucidated through spectroscopic analysis, and their absolute configurations were unambiguously determined by a combination of single-crystal X-ray crystallography, Rh 2 (OCOCF 3 ) 4 -induced ECD experiments, ECD calculations, and modified Mosher methods. Compound 2 (5 μM) was found to have a significant hypoxia-protective effect that improved the survival rate of hypoxia/reoxygenation-treated human umbilical vein endothelial cells from 35% to 70%, which was equal to the potency of the positive control, verapamil. Flow cytometry analysis suggested 2 could inhibit H/R-induced late-stage apoptosis of this cell line.