Preparation of 4-Retinamidophenyl- and 4-Retinamidobenzyl-C-glycosyl and C-Glucuronosyl Analogues of the Glucuronide of 4-Hydroxyphenyl-Retinamide as Potential Stable Cancer Chemopreventive Agents

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Abstract
Glucuronide metabolites of retinoic acid and its analogues have been suggested to be active cancer chemopreventive analogues of the parent molecules. However, these metabolites are susceptible to β-glucuronidase and acid-catalyzed cleavage and it is not clear whether these carbohydrate 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 breast cancer chemopreventive agent 4-hydroxyphenylretinamide (4-HPR) are outlined. The chemical and enzymatic stability of these compounds has been evaluated relative to the glucuronide of 4-HPR.