Synthesis of 3-Hydroxy-3-cyclohexylbutyric Acid Derivatives. 2. Cyclic Analogues of Mevalonic Acid

Article abstract of DOI:10.1021/jm00366a021

The sodium salt of (Z)-3-hydroxy-3-(2-hydroxycyclohexyl)butyric acid (I) and its lactone (II) were prepared through the corresponding tert-butyl ester by hydrogenation, over Rh/Al2O3 catalyst, of the phenyl ring of tert-butyl 3-hydroxy-3-(2-hydroxyphenyl)butyrate (III). (Z)-3-Hydroxy-3-(2-methoxycyclohexyl)butyric acid was prepared similarly. (Z)-4-Methyloctahydro-2H-1-benzopyran-2-one was prepared by hydrogenation, over Rh/Al2O3 catalyst, of 4-methylcoumarine, prepared in turn from III by a one-pot procedure comprising hydrolysis, lactonization, and dehydration.The above compounds inhibit acetate incorporation in cholesterol and fatty acids in rat liver slices at 5 * 10^-3 M, but they lack specific inhibitory activity on HMG-CoA reductase.