Diversity-oriented total synthesis of Riccardin C and development of its analogs

Abstract

Liver X receptors (LXRα and β) play critical roles in cholesterol metabolism via controlling the related gene expression. Therefore, LXR is one of the significant molecular targets for the development of drugs for life-style related diseases. Recently, Riccardin C, a bisbibenzyl natural product isolated from liverworts, was reported to have LXRα-selective agonistic activity (T. Mogami, et al., FEBS Lett., 2005, 579, 5299-5304). In this study, diversity-oriented total synthesis of Riccardin C was carried out by using some ring-closure methodology in the critical macrocyclization. The synthetic method using S_NAr coupling reaction as the key ring-closing reaction succeeded in the synthesis of Riccardin C with 5.3% of overall yield (16 steps). The method is useful to apply the synthesis of various Riccardin C derivatives.