title: 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.
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.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore).
authors.forename: Dewi
authors.initials: D
authors.lastname: Susanti
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao (China).
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore).
authors.forename: Weidong
authors.initials: W
authors.lastname: Rao
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China).
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong (China).
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao (China). duncanleung@umac.mo.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
authors.affiliation: School of Chemistry, Monash University, Clayton, Victoria 3800 (Australia). phil.chan@monash.edu, P.W.H.Chan@warwick.ac.uk.|Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK). phil.chan@monash.edu, P.W.H.Chan@warwick.ac.uk.|Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore). phil.chan@monash.edu, P.W.H.Chan@warwick.ac.uk.
authors.forename: Philip Wai Hong
authors.initials: PW
authors.lastname: Chan
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D016207:Cytokines / Q000737:chemistry*; D004952:Esters; D006046:Gold / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D054833:Isoindoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000737:chemistry*; D015394:Molecular Structure; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000480:Alkynes; D016207:Cytokines; D004952:Esters; D054833:Isoindoles; D014409:Tumor Necrosis Factor-alpha; D006046:Gold
keywords: alkynes; cycloisomerization; cytokine antagonists; gold; homogeneous catalysis