Chloropupukeanolides C–E: Cytotoxic Pupukeanane Chlorides with a Spiroketal Skeleton from <i>Pestalotiopsis fici</i>

Abstract

Abstract Chloropupukeanolides C–E ( 8 – 10 ), three highly functionalized secondary metabolites featuring a novel spiroketal skeleton derived from the chlorinated tricyclo‐[4.3.1.0 3, 7 ]‐decane (pupukeanane) and the 2,6‐dihydroxy‐4‐methylbenzoic acid moieties, were isolated from the scale‐up fermentation extract of the plant endophytic fungus Pestalotiopsis fici . The constitutions of compounds 8 – 10 were elucidated primarily by NMR experiments. Their relative configurations were deduced by analogy to metabolites 4 – 6 , which were previously isolated from the same fungus. The absolute configuration of 8 was assigned by X‐ray crystallography and those of 9 and 10 by quantum‐chemical CD calculations. Biogenetically, chloropupukeanolides C–E ( 8 – 10 ) are presumably derived from the same oxidation‐induced Diels–Alder reaction pathway as compounds 1 and 4 – 7 , via the putative biosynthetic precursors 2 and 3 . The opposite configurations of the complete “Southern parts” of 8 and 9 suggests that this Diels–Alder reaction is stereochemically not very selective. Compounds 8 – 10 showed significant cytotoxicity against a small panel of human tumor cell lines and weak activities against the pathogens of tropical diseases.