Chlorotheolides A and B, Spiroketals Generated via Diels–Alder Reactions in the Endophytic Fungus Pestalotiopsis theae

Chlorotheolides A (1) and B (2), two new spiroketals possessing the unique [4,7]methanochromene and dispiro-trione skeletons, respectively, and their putative biosynthetic precursors, 1-undecen-2,3-dicarboxylic acid (3) and maldoxin (4), were isolated from the solid substrate fermentation of the plant endophytic fungus Pestalotiopsis theae (N635). Their structures were elucidated based on NMR spectroscopic data and electronic circular dichroism calculations. Biogenetically, compounds 1 and 2 could be generated from the co-isolated 3 and 4 via Diels–Alder reactions. Chlorotheolide (2) showed an antiproliferative effect against the human tumor cell line HeLa and induced an autophagic process in the cells.