title: Total synthesis and dual PPARα/γ agonist effects of amorphastilbol and its synthetic derivatives.
abstract: 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.
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors.forename: Taejung
authors.initials: T
authors.lastname: Kim
authors.forename: Woojung
authors.initials: W
authors.lastname: Lee
authors.forename: Kyu Hyuk
authors.initials: KH
authors.lastname: Jeong
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Song
authors.forename: Soon-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Pilju
authors.initials: P
authors.lastname: Choi
authors.forename: Su-Nam
authors.initials: SN
authors.lastname: Kim
authors.forename: Seokjoon
authors.initials: S
authors.lastname: Lee
authors.forename: Jungyeob
authors.initials: J
authors.lastname: Ham
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001881:Borates / Q000737:chemistry; D002186:Cannabinoids / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D031301:Robinia / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D001881:Borates; D002186:Cannabinoids; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D010936:Plant Extracts; D013267:Stilbenes; C575104:amorphastilbol