Amorphastilbol derived from Amorpha fruticosa : Total synthesis and biological evaluation of dual PPAR α/γ agonist

Abstract

Peroxisome proliferator–activated receptors (PPARs) are ligand-activated transcription factors involved in the transcriptional regulation of key metabolic pathways such as lipid metabolism, adipogenesis, and insulin sensitivity. Three PPAR isotypes have been identified α, γ, and δ. The amorphastilbol (APH-1) is a small molecules of natural stilbene isolated from the Amorpha fruticosa, and stimulates PPARα/γ transcriptional activity at the lower concentration than previously reported natural PPARs ligands. Therefore, we focused on the total synthesis of APH-1 from RPU extract (0.04% yield) and its derivatives and their biological evaluation as PPAR transcriptional activators.