Document Type

Journal Article

Department/Unit

Department of Chemistry

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

Language

English

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.

Keywords

alkynes, cycloisomerization, cytokine antagonists, gold, homogeneous catalysis

Publication Date

2015

Source Publication Title

Chemistry - A European Journal

Volume

21

Issue

25

Start Page

9111

End Page

9118

Publisher

Wiley-VCH Verlag

DOI

10.1002/chem.201500795

Link to Publisher's Edition

http://dx.doi.org/10.1002/chem.201500795

ISSN (print)

09476539

ISSN (electronic)

15213765

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