Total synthesis and dual PPAR alpha/gamma agonist effects of Amorphastilbol and its synthetic derivatives

Abstract

Amorphastilbol (APH-1), isolated from a Robinia pseudoacacia var. umbraculifer seed extract, is a biologically interesting natural trans-stilbene compound with dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist activity. After total synthesis of APH-1 and its derivatives by Pd-catalyzed Suzuki-Miyaura cross-coupling of a common (E)-styryl bromide intermediate and various aromatic trifluoroborate compounds, we biologically evaluated APH-2-APH-12 for PPAR agonist activity. APH-4 and APH-11 were effective PPAR alpha/gamma transcriptional activators, compared with APH-1. Therefore, we suggest that APH-4 and APH-11 are novel dual PPAR alpha/gamma agonists and are potentially useful for treating type 2 diabetes by enhancing glucose and lipid metabolism. (C) 2012 Elsevier Ltd. All rights reserved.