PREPARATION OF 4-RETINAMIDOPHENYL- AND 4-RETINAMIDOBENZYL-C-GLYCOSYL AND C-GLUCURONOSYL ANALOGS OF THE GLUCURONIDE OF 4-HYDROXYPHENYL-RETINAMIDE AS POTENTIAL STABLE CANCER CHEMOPREVENTIVE AGENTS

Glucuronide metabolites of retinoic acid and its analogues have been s uggested to be active cancer chemopreventive analogues of the parent m olecules. However, these metabolites are susceptible to beta-glucuroni dase and acid-catalyzed cleavage and it is not clear whether these car bohydrate conjugates must be hydrolyzed back to the parent molecule to show activity. Thus, the multistep syntheses of stable C-glycosyl and C-glucuronosyl analogues of the known glucuronide metabolite of the b reast cancer chemopreventive agent 4-hydroxyphenylretinamide (4-HPR) a re outlined. The chemical and enzymatic stability of these compounds h as been evaluated relative to the glucuronide of 4-HPR.