Synthesis and biological evaluation of demethyl-retinoic acids

Abstract

A palladium catalyzed coupling reaction of enol triflates, derived from cyclohexanones, with a tetraenyl stannyl ester in the presence of cesium fuloride afforded 9Z-demethyl retinoates in good yields. These esters were converted to the corresponding acids by basic hydrolysis, and then the biological activities of the synthetized demethyl-retinoic acids were evaluated. All demethyl-retinoic acids had no antiproliferative, differentiation-inducing, and apoptosis-inducing activities. However, all demethyl-retinoic acids showed higher transcriptional activity for the retinoid X receptor responsive element gene than did 9Z-retinoic acid (a natural ligand) and 5-demethyl retinoic acid (3a) exhibited the highest transcriptional activity among all demethyl-retinoic acids.