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.