Convenient Synthesis of Biologically Important Retinoids

The toxic and teratogenic effects caused by the highly biologically active (all‐E)‐retinoic acid and its derivatives prompted us to synthesize a number of retinoids. We developed synthetic approaches to (all‐E)‐retinyl β‐D‐glucuronide 3, methyl (retinoyl β‐D‐glucopyranoside)uronate 5, (all‐E)‐retinoic acid β‐D‐glucopyranosyl ester 8 and (all‐E)‐retinoyl β‐D‐glucuronide 6 in high purity and yield. Compound 3 was synthesized under Koenigs‐Knorr conditions from (all‐E)‐retinol and an α‐halogenose. Compounds 5 and 8 were prepared by esterification of a silver salt of (all‐E)‐retinoic acid with an α‐glycosyl halide in pyridine. (all‐E)‐Retinoyl β‐D‐glucuronide 6 was prepared by reaction of (all‐E)‐retinoyl fluoride with underivatized β‐D‐glucuronic acid. Compounds 5, 6 and 8 show biological effects similiar to those of retinoic acid.