Design and synthesis of novel alkene based liver X receptor ligands

Liver X receptor (LXR), a member of a nuclear receptor superfamily of proteins, regulates a variety of metabolic processes including efflux of cholesterol and synthesis of fatty acids by regulating the transcription of genes involved in these processes. The primary step of the gene transcription involves binding of a small molecule ligand to the receptor, which triggers a conformational change of the receptor and leads to its binding to the coactivator proteins. We are synthesizing a library of ligands of various shapes and sizes, which will be used to control the binding of coactivator proteins to LXR. We have synthesized several 3-halo-3-substituted allylic alcohols and explored the modifications of these scaffolds using palladium-catalyzed coupling reactions at the vinyl halide position, as well as alkylations and Mitsunobu reactions at the alcohol position. The results of these studies are presented.