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Gold‐Catalyzed Cycloisomerization and Diels–Alder Reaction of 1,4,9‐Dienyne Esters to 3 a,6‐Methanoisoindole Esters with Pro‐Inflammatory Cytokine Antagonist Activity
Author(s) -
Susanti Dewi,
Liu LiJuan,
Rao Weidong,
Lin Sheng,
Ma DikLung,
Leung ChungHang,
Chan Philip Wai Hong
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500795
Subject(s) - cycloisomerization , chemistry , tumor necrosis factor alpha , catalysis , diels–alder reaction , derivative (finance) , antagonist , cytokine , receptor , stereochemistry , biochemistry , biology , immunology , economics , financial economics
A synthetic method to prepare 3a,6‐methanoisoindole esters efficiently by gold(I)‐catalyzed tandem 1,2‐acyloxy migration/Nazarov cyclization followed by Diels–Alder reaction of 1,4,9‐dienyne esters is described. We also report the ability of one example to inhibit binding of tumor necrosis factor‐α (TNF‐α) to the tumor necrosis factor receptor 1 (TNFR1) site and TNF‐α‐induced nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) activation in cell at a half‐maximal inhibitory concentration (IC 50 ) value of 6.6 μ M . Along with this is a study showing the isoindolyl derivative to exhibit low toxicity toward human hepatocellular liver carcinoma (HepG2) cells and its possible mode of activity based on molecular modeling analysis.