ABSTRACT: Cytospolides F-Q (6-17) and decytospolides A and B (18 and 19), 14 unusual nonanolide derivatives, were isolated from Cytospora sp., an endophytic fungus from Ilex canariensis. The structures were elucidated by means of detailed spectroscopic analysis, chemical interconversion, and X-ray single crystal diffraction. The solution- and solid-state conformers were compared by the combination of experimental methods (X-ray, NMR) supported by DFT calculations of the conformers. Absolute configurations were assigned using the modified Mosher's method and solution- and solid-state TDDFT ECD calculations. In an in vitro cytotoxicity assay toward the tumor cell lines of A549, HCT116, QGY, A375, and U973, the γ-lactone 17 demonstrated a potent growth inhibitory activity toward the cell line A-549, while nonanolide 16 with (2S) configuration showed the strongest activity against cell lines A-549, QGY, and U973. A cell cycle analysis indicated that compound 16 can significantly mediate G1 arrest in A549 tumor cells, confirming the important role of the C-2 methyl in the growth inhibition toward the tumor line. The discovery of an array of new nonanolides demonstrates the productivity of the fungus, and it is an example of chemical diversity, extending the nonanolide family by derivatives formed by ring cleavage, oxidation, esterification, and Michael addition.
The Journal of Organic Chemistry 12/2011; 76(23):9699-710. · 4.45 Impact Factor