Synthesis of 3-hydroxy-3-cyclohexylbutyric acid derivatives. 2. Cyclic analogues of mevalonic acid

J Med Chem. 1983 Dec;26(12):1767-9. doi: 10.1021/jm00366a021.

Abstract

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.

MeSH terms

  • Animals
  • Cholesterol / biosynthesis
  • Hydroxybutyrates / chemical synthesis*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver / metabolism
  • Mevalonic Acid / analogs & derivatives*
  • Mevalonic Acid / chemical synthesis
  • Mevalonic Acid / pharmacology
  • Rats

Substances

  • Hydroxybutyrates
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 3-hydroxy-3-cyclohexylbutyric acid
  • Cholesterol
  • Mevalonic Acid