Synthesis of highly potent RXR-specific retinoids: The use of a cyclopropyl group as a double bond isostere

Retinoids act through two distinct hormonal pathways activated by RAR and RXR ligands. We describe the synthesis of C9---C10 locked retinoid analogs, including the most potent RXR - specific agonist known to date (Compound 5), and discuss the structural features that lead to this specificity.