Cytotoxic dehydromonacolins from red yeast rice.

Two new dehydromonacolins (1 and 3), together with nine known monacolins (4-12), were isolated from red yeast rice. Compounds 4-6 were isolated from a natural resource for the first time. Their structures were elucidated by means of NMR and mass spectroscopic analyses. The structure of dehydromonacolin N (1) was further confirmed by its semisynthesis from monacolin K (lovastatin) (11). Dehydromonacolin J (2), an intermediate in the semisynthesis of 1, was obtained as a new dehydromonacolin. The structure of dehydromonacolin L (3) was also confirmed by an elimination reaction of monacolin L (12). Compound 1, possessing a C2 side chain, is unprecedented in the natural monacolin family and exhibited moderate cytotoxic activity against Hep G2, Caco-2, and MCF-7 cancer cell lines. Dehydromonacolin K (8) demonstrated the most potent cytotoxicity to all three of these cell lines. The structure-activity relationship of natural and synthesized monacolins was discussed. This is the first report on the cytotoxic effects of dehydromonacolins.