Synthesis of the 4-oxygenated retinoid metabolites.

The efficient synthesis of 4-hydroxylated metabolites of various retinoids is described. Allylic bromination of beta-ionone, retinal, and methyl retinoate followed by treatment with aqueous AcOH and saponification afforded the 4-hydroxy analogues in 64-79% yields. With the conjugated polyenes, retinal and methyl retinoate, about 25% of the products were found to be the 13-cis isomers. Purification of isomer mixtures by HPLC permitted stereochemical assignments after 1H NMR analysis.