Synthesis of 3-hydroxy-3-cyclohexylbutyric acid derivatives. 2. Cyclic analogues of mevalonic acid.
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 X 10(-3) M, but they lack specific inhibitory activity on HMG-CoA reductase.
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D006885:Hydroxybutyrates / Q000138:chemical synthesis*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000378:metabolism; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats
D006885:Hydroxybutyrates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C039844:3-hydroxy-3-cyclohexylbutyric acid; D002784:Cholesterol; D008798:Mevalonic Acid