Chloropestolide A, an Antitumor Metabolite with an Unprecedented Spiroketal Skeleton from <i>Pestalotiopsis fici</i>

Chloropestolide A (1), a highly functionalized spiroketal with an unprecedented skeleton derived from a chlorinated bicyclo-[2.2.2]-oct-2-en-5-one ring and a 2,6-dihydroxy-4-methylbenzoic acid unit, has been isolated from the scale-up fermentation extract of Pestalotiopsis fici. The structure of 1 was elucidated by NMR spectroscopy and X-ray crystallography. 1 could be derived from the same Diels−Alder precursors as 2 and showed significant inhibitory effects on growth of two human cancer cell lines, HeLa and HT29, with GI50 values of 0.7 and 4.2 μM, respectively.