SYNTHESES OF HIGH SPECIFIC ACTIVITY 2,3-[H-3](2)-9-CIS-RETINOIC-ACID AND 3,4-[H-3](2)-9-CIS-RETINOIC-ACID

B-cis-Retinoic acid (9-cis-RA) is an endogenous hormone which binds an d activates the retinoic acid receptors (RARs) and the retinoic X rece ptors (RXRs). In order to investigate the function of 9-cis-RA in vitr o and in vivo high specific activity labeled 9-cis-RA was prepared. Tw o tritium labels were efficiently introduced at the 2,3- or 3,4-positi ons, respectively, in the cyclohexene ring moiety resulting in labeled 9-cis-RA with specific activity of 58-60 Ci/mmol. The critical ring-l abeling step relies on a highly regioselective tritiation of either a terminal or an isolated double bond in the presence of the conjugated retinoate side chain. Moreover, the labeling is performed at the penul timate synthetic step resulting in optimization of radiochemical yield s and ease of synthesis. This is the first reported synthesis of ring- labeled [H-3](2)-9-cis-RA, and the methodology described herein is app licable to the synthesis of other retinoic acid isomers.