Total synthesis and dual PPARα/γ agonist effects of amorphastilbol and its synthetic derivatives
- Bioorg Med Chem Lett. 2012 Jun 15;22(12):4122-6. doi: 10.1016/j.bmcl.2012.04.062.
- 1. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
Amorphastilbol (APH-1), isolated from a Robinia pseudoacacia var. umbraculifer [corrected] seed extract, is a biologically interesting natural trans-stilbene compound with dual Peroxisome Proliferator-activated Receptor (PPAR) α/γ 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 PPARα/γ transcriptional activators, compared with APH-1. Therefore, we suggest that APH-4 and APH-11 are novel dual PPARα/γ agonists and are potentially useful for treating type 2 diabetes by enhancing glucose and lipid metabolism.