RECENT IMPROVEMENTS TOWARDS THE SYNTHESIS OF THE C-GLUCURONOSYL CANCER CHEMOPREVENTIVE (β-d-GLUCOPYRANOSYLURONATE)-4-RETINAMIDOPHENYLMETHANE
| Autor: | K. L. Weiss, Robert W. Curley, M. F. Wong |
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| Rok vydání: | 1996 |
| Předmět: | |
| Zdroj: | Journal of Carbohydrate Chemistry. 15:763-768 |
| ISSN: | 1532-2327 0732-8303 |
| Popis: | Evidence suggests that the glucuronide conjugates of retinoids may be active metabolites of the parent compounds with potential utility as drugs.1 We have recently shown that the O-glucuronide metabolite 1 of the synthetic retinoid N-4-hydroxyphenylretinamide (2) shows reduced toxicity and a significant chemopreventive advantage relative to the parent retinoid in a carcinogen-induced rat mammary cancer model.2 In efforts to determine whether these conjugates function as intact molecules or must be hydrolyzed back to 2, we designed and synthesized a series of C-glycosyl and C-glucuronosyl analogues of 1 3. Our syntheses of these compounds are lengthy (10-12 steps) and lead to the desired products in less than 4% overall yields. Limitations on the availability of these compounds led us to evaluate them using a modified protocol for the carcinogen-induced rat mammary tumor model. While many of our analogues showed cancer chemopreventive activity in this assay, C-glucuronosyl analogue 3 has proven to be the m... |
| Databáze: | OpenAIRE |
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