5 ACAT阻害剤terpendole類の構造と活性(口頭発表の部)

概要

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During our continuous screening for acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors of microbial origin, a soil-isolated new genus fungus, Albophoma yamanashiensis, was found to produce a new series of ACAT inhibitors named terpendoles A〜L (1〜12). Structures of 1〜12 were elucidated by NMR and other spectroscopic studies. They consist of diterpene and indole moieties in common like indoloditerpene group of paspaline (13) and emindole SB (14). Compounds 5〜7 had the same carbon skeleton as 13. One methyl residue of 13 was removed to form epoxide in 2, 8 and 9 and additional isoprene unit was bonded to them in 4 and 10. The additional isoprene was cyclized to form 1,3-dioxane in 1, 3 and 11 and 12 had one more prenyl residue at indole. The relative configurations of 3, 4 and 5 were confirmed by NOE experiments and X-ray crystallographic analyses. Compounds 3 and 4 showed the most potent ACAT inhibitory activity with an IC_<50> value of 2.1μM and 3.2μM, respectively in an in vitro enzyme assay. Two known compounds, 13 and 14, were also isolated from the culture broth of the producer. But they showed weak activities. Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that 4 inhibited the formation of cholesterylester specifically.
天然有機化合物討論会の論文
1994-09-20