We intend to devise concise and efficient laboratory syntheses of biologically active compounds representing three unrelated classes of natural products. The products of this study are phyllanthocin [the aglycone of the promising antileukemic agent phyllanthocide - in vivo activity aganst P388 leukemia in mice (30-40 percent increase in life span) and against B16 melanoma in mice (60-90 percent increase in life span)], nagilactone F (representing the nagilactone diterpenoid dilactones which show activity as antitumor agents, plant growth promoters, and insect larvae toxins), and the compounds dihydromevinolin and dihydrocompactin (potent competitive inhibitors of HMG-CoA reductase, the enzyme involved in the rate-limiting step of cholesterol biogenesis). The synthetic routes proposed should lead to the target molecules in enantiomerically homogeneous states. The methods to be developed, expanded, and applied include intramolecular cycloadditions, sigmatropic rearrangements, polyene cyclizations organosilicon-mediated reactions, and the use of chiral carbohydrate templates.
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