The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist

Abstract A concise route to the pregnane X receptor (PXR) agonist solomonsterol B, a natural product isolated from the marine sponge Theonella swinhoei , has been developed starting from commercially available hyodeoxycholic acid. The synthesis features a one‐carbon side chain degradation and the refunctionalization of the A and B rings to install the desired trans junction and the two hydroxy groups at C2 and C3 in a trans relationship. The protocol proceeded with good yields (10 % over 13 steps), also allowing the preparation of a side chain‐modified derivative useful for a preliminary structure–activity relationship on PXR. The pharmacological characterization of solomonsterol B demonstrated that this compound was a PXR agonist in a transactivation assay, and when it was incubated with liver cells, it increased the expression of PXR‐regulated genes. These data support the development of sponge steroids as PXR ligands endowed with therapeutic potential.