Synthesis of riccardin C and its seven analogues. Part 1: The role of their phenolic hydroxy groups as LXRα agonists

Riccardin C and its 7 analogues were synthesized. The structure–activity relationship of these compounds indicated that all hydroxy groups in riccardin C are essential for its binding to LXRα. Riccardin C, a nuclear receptor LXRα selective agonist, is an 18-membered macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin C and its seven O-methylated derivatives was accomplished. The synthetic sequence highlights an intramolecular Suzuki–Miyaura coupling in the formation of the 18-membered biaryl linkage present in riccardin C. The structure–activity relationship of these compounds suggests that all of the phenolic hydroxy groups present in riccardin C are essential for the activation of LXRα.