Natural ligands of RXR receptors.

Given the role of retinoid X receptors (RXRs) as promiscuous partners of heterodimeric complexes with other members of the Nuclear Receptor (NR) superfamily, RXR ligands (rexinoids) play fundamental roles in gene transcription, since upon ligand binding either transcriptionally activate the "permissive" subclass of heterodimers or synergize with partner ligands in the "non-permissive" subclass of heterodimers. The collection of natural products thus far reported to bind RXR are described, including those discovered by high-throughput screening (HTS), mere serendipity, and a combination of those. Detailed protocols for the diastereo- and enantioselective synthesis of (R)-9-cis-13,14-dihydroretinoic acid, a putative natural RXR ligand, are provided.