Synthesis and structure-activity relationship of violaceoid D, a cytotoxic alkylated phenol isolated from Aspergillus violaceofuscus Gasperini.

The enantioselective synthesis of violaceoid D, a cytotoxic phenolic compound isolated from the culture broth of Aspergillus violaceofuscus Gasperini, was achieved. The total synthesis involves stereoselective construction of the stereogenic center of violaceoid D via Sharpless asymmetric dihydroxylation, followed by Smiles rearrangement. The absolute configuration of natural violaceoid D was determined to be R from the specific rotation value. Synthesized violaceoid D and its analogs were evaluated for cytotoxicity against two human cancer cell lines, Jurkat and HCT116. Because the enantiomer of violaceoid D showed no cytotoxicity, it is plausible that violaceoid D binds selectively to specific target molecules, such as proteins in the cancer cells.

Synthesis and cytotoxic activities of 8- and 6-demethyleucalyptins.

Secondary metabolites in plants influence the health of herbivores such as Japanese rock ptarmigans that feed on the leaves and fruits of alpine plants. Thus, it is important to understand the secondary metabolites of alpine plants and their biological activities for conserving Japanese rock ptarmigans. We isolated C-methylflavone from the leaves of Kalmia procumbens, on which Japanese rock ptarmigans feed. Although its structure was deduced to be 8-demethyleucalyptin by comparing its nuclear magnetic resonance (NMR) data with the reported ones, the possibility that the isolated compound is 6-demethyleucalyptin cannot be ruled out. Thus, both isomers were synthesized. The isolated compound was unambiguously determined to be 8-demethyleucalyptin by comparing its NMR data with those of the synthetic ones. Cytotoxic evaluation of 8- and 6-demethyleucalyptins revealed that only the former showed cytotoxicity against HCT116 and MRC-5 cells. The present study provides not only easy access to 8- and 6-demethyleucalyptins, but also their biological information.