Unreported cytochalasins from an acid-mediated transformation of cytochalasin J isolated from Diaporthe cf. ueckeri.

Chemical investigation of an endophytic fungus herein identified as Diaporthe cf. ueckeri yielded four known compounds, named cytochalasins H and J and dicerandrols A and B. Reports of acid sensitivity within the cytochalasan family inspired an attempt of acid-mediated conversion of cytochalasins H and J, resulting in the acquisition of five polycyclic cytochalasins featuring 5/6/5/8-fused tetracyclic and 5/6/6/7/5-fused pentacyclic skeletons. Two of the obtained polycyclic cytochalasins constituted unprecedented analogues, for which the trivial names cytochalasins J and J were proposed, whereas the others were identified as the known phomopchalasin A, phomopchalasin D and 21-acetoxycytochalasin J. The structures of the compounds were determined by extensive spectral analysis, namely HR-ESIMS, ESIMS and 1D/2D NMR. The stereochemistry of cytochalasins J and J was proposed using their ROESY data, biosynthetic and mechanistic considerations and by comparison of their ECD spectra with those of related congeners. All compounds except for cytochalasins H and J were tested for antimicrobial and cytotoxic activity. Cytochalasins J and J showed neither antimicrobial nor cytotoxic activity in the tested concentrations, with only weak antiproliferative activity observable against KB3.1 cells. The actin disruptive properties of all cytochalasins obtained in this study and of the previously reported cytochalasins RKS-1778 and phomopchalasin N were examined, and monitored by fluorescence microscopy using human osteo-sarcoma (U2-OS) cells. Compared to their precursor molecules (cytochalasins H and J), phomopchalasins A and D, 21-acetoxycytochalasin J, cytochalasins J and J revealed a strongly reduced activity on the F-actin network, highlighting that the macrocyclic ring is crucial for bioactivity.