Synthesis of 3-hydroxy-3-cyclohexylbutyric acid derivatives. 1. Cyclic homologues of 3-hydroxy-3-methylglutaric acid.
Z and E isomers of 3-methyl-3-(carboxymethyl)hexahydro-1 (3H)-isobenzofuranones (I), lactones of 3-hydroxy-3-(2-carboxycyclohexyl) butyric acids (II), were prepared and tested on cholesterol biosynthesis in vitro. Compound I of the Z series was prepared through its ethyl ester by hydrogenation, over Rh/Al2O3 catalyst, of the phenyl ring of 3-methyl-3-[(ethoxycarbonyl)methyl]-1(3H)-isobenzofuranone. Compound I of the E series was prepared, through its ethyl ester, by Reformatsky reaction from ethyl (E)-2-acetylcyclohexanecarboxylate. 3-Methyl-3-(carboxymethyl)-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, 3-methyl-3-ethyl-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, and 3-methyl-3-(carboxymethyl)-1(3H)-isobenzofuranone were also prepared and tested. The above compounds inhibited acetate incorporation in cholesterol and fatty acids in rat liver slices at 5 X 10(-3) M but lack specific inhibitory activity on HMG-CoA reductase.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D005977:Glutarates / Q000138:chemical synthesis*; D006885:Hydroxybutyrates / Q000138:chemical synthesis*; D007536:Isomerism; D008099:Liver / Q000378:metabolism; D008297:Male; D015093:Meglutol / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D051381:Rats
D000085:Acetates; D005977:Glutarates; D006885:Hydroxybutyrates; C039844:3-hydroxy-3-cyclohexylbutyric acid; D002784:Cholesterol; D015093:Meglutol