Bioactive Nonanolide Derivatives Isolated from the Endophytic FungusCytosporasp.

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.

Incensfuran: isolation, X-ray crystal structure and absolute configuration by means of chiroptical studies in solution and solid state

“…Consequently, all uncertainties related to the conformational search are avoided. Over the last decade, it has been shown that this methodology is particular benecial for exible medium-size natural products, 5,[9][10][11][12][13][14][15][16] and can be also applied to differentiate the conformational polymorphic forms of active pharmaceutical ingredients. 17 In Fig.…”

Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an <i>in Situ</i> Protecting Groups

“…66) Decytospolide B shows in vitro cytotoxic activity toward tumor cell lines A549 and QGY. There are two reports of the total synthesis of these natural products; the synthetic routes involve multiple steps.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…Zhang et al . in 2011 initially isolated a family of nonanolides, so‐called cytospolides, by simple extraction by acetone from Cytospora sp. Which is an endophytic fungus from an ever green shrub (Ilex canariensis) found on the island of Gomera, Spain several molecules present in this family exhibited cytotoxic potency to diverse human carcinogenic cell lines.…”

“…Among them, Cytospolide P ( 136 ) is the most active member in the wide variety of cytospolides family, showing powerful inhibitory potency for the human lung carcinogenic cell line A‐549. Noticeably, target 136 has an interesting structure as a 10‐membered lactone entrenched with four chiral centers wherever the C‐5 ‐OH remains in acetate‐protected form. Notably, the presence of a further –CH 3 group situated at the C‐2 in 136 is exclusive among the members of the cytospolide family since it is absent in other nonanolide families .…”

“…Notably, the presence of a further –CH 3 group situated at the C‐2 in 136 is exclusive among the members of the cytospolide family since it is absent in other nonanolide families . It is clear that the stereochemistry of the C‐2 –CH 3 group plays an important role in the biological behavior of the molecules in the cytospolides family …”