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 |
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| Authors: | Dewi Susanti Li‐Juan Liu Dr Weidong Rao Sheng Lin Prof?Dr Dik‐Lung Ma Prof?Dr Chung‐Hang Leung Prof?Dr Philip Wai Hong Chan |
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| Institution: | 1. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore);2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao (China);3. Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China);4. School of Chemistry, Monash University, Clayton, Victoria 3800 (Australia);5. Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK) |
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| Abstract: | 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 (IC50) value of 6.6 μM . 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. |
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| Keywords: | alkynes cycloisomerization cytokine antagonists gold homogeneous catalysis |
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