Diphenylemestrins A−E: Diketopiperazine-Diphenyl Ether Hybrids from Aspergillus nidulans

Chemical investigation on the secondary metabolites of Aspergillus nidulans led to the identification of five new dioxopiperazine-diphenyl ether hybrids, diphenylemestrins A−E (1−5). Compounds 1−5 represent the first dimers of dioxopiperazine and diphenyl ether, the diphenyl ether moiety in compound 4 was a rare dibenzofuran. Their structures and absolute stereochemistry were determined by spectroscopic data and electronic circular dichroism (ECD) calculations. Diphenylemestrin C (3) showed moderate cytostatic effect against NB4 cells with IC₅₀ value of 21.99 μM and induced apoptosis at a higher concentration.