Vitamin A derivatives / Retinoic acid derivatives / Tumor inhibitors / Koenigs-Knorr reaction / Glucuronides
The toxic and teratogenic effects caused by the highly biolo-synthesized under Koenigs-Knorr conditions from (all-E)-retigically active (all-E)-retinoic acid and its derivatives n&l and an a-halogenose. Compounds 5 and 8 were prepared prompted us to synthesize a number of retinoids. We develo-by esterification of a silver salt of (all-E)-retinoic acid with an ped synthetic approaches to (all-E)-retinyl p-D-glucuronide 3, a-glycosyl halide in pyridine. (all-E)-Retinoyl P-D-glucuromethyl (retinoyl p-D-g1ucopyranoside)uronate 5, (all-E)-reti-nide 6 was prepared by reaction of (all-E)-retinoyl fluoride noic acid P-D-glucopyranosyl ester 8 and (all-E)-retinoyl pwith underivatized P-D-glucuronic acid. Compounds 5,6 and D-glucuronide 6 in high purity and yield. Compound 3 was 8 show biological effects similiar to those of retinoic acid.
Retinol, retinoic acid and their derivatives are involved in processes of controlling growth and differentiation of normal and neoplastic cells through interaction with a nuclear receptor. In addition to the high biological activity, toxicity and teratogenic effects of retinoic acid and some of it's derivatives, it is known that there are problems arising in the application of these substances. New retinoids are to be synthesized, combining bioavailability in a wide range of aqueous cell compartments with a reduction of toxic and teratogenic effects.
The synthesis of some polar and highly biologically active retino-According to well-known ~trategies[~-~] applied in the synthesis of (a/l-E)-retinyl pwglucuronide 3, (al/-E)-retinoic acid p-D-glUCOpyranosyl ester 8 and (all-E)-retinoyl p-D-ghcuronide 6 we optimized a variety of convenient methods, and obtained higher yields of the expected retinoids than previously reported. will be discussed.
COOCH3 COOH
During the synthesis of methyl (2,3,4-tri-O-acetyl-I-retinoyl p-D-g1ucopyranoside)uronate 4, (all-E)-retinoic acid had to be converted into a silver salt by treatment with silver(1) oxide in pyridine. Under exclusion of air, light, heat and acidic conditions, 82Y0 of the esterification product was obtained (compound 4).