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Cytotoxic Dehydromonacolins from Red Yeast Rice

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journal contribution
posted on 01.02.2012, 00:00 by Lin Zhu, Lee-Fong Yau, Jing-Guang Lu, Guo-Yuan Zhu, Jing-Rong Wang, Quan-Bin Han, Wen-Luan Hsiao, Zhi-Hong Jiang
Two new dehydromonacolins (1 and 3), together with nine known monacolins (412), were isolated from red yeast rice. Compounds 46 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.