Synthesis of novel fluorophenylaryl / heteroaryl ether derivatives

Gold complexes with N-heterocyclic carbene (NHC) ligands represent a promising class of metallodrugs for the treatment of cancer or infectious diseases. In this report, the synthesis and the biological evaluation of halogen-containing NHC-Au -Cl complexes are described. The complexes 1 and 5 a-5 f displayed good cytotoxic activity against tumor cells, and cellular uptake studies suggested that an intact Au-NHC fragment is essential for the accumulation of high amounts of both the metal and the NHC ligand. However, the bioavailability was negatively affected by serum components of the cell culture media and was influenced by likely transformations of the complex. One example (5 d) efficiently induced apoptosis in vincristine- and daunorubicin-resistant P-glycoprotein overexpressing Nalm-6 leukemia cells. Cellular uptake studies with this compound showed that both the wild-type and resistant Nalm-6 cells accumulated comparable amounts of gold, indicating that the gold drug was not excreted by P-glycoprotein or other efflux transporters. The effective inhibition of mammalian and bacterial thioredoxin reductases (TrxR) was confirmed for all of the gold complexes. Antibacterial screening of the gold complexes showed a particularly high activity against Gram-positive strains, reflecting their high dependence on an intact Trx/TrxR system. This result is of particular interest as the inhibition of bacterial TrxR represents a relatively little explored mechanism of new anti-infectives.

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Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram‐Positive Directed Antibacterial Effects

Schmidt

Karge

Misgeld

et al. 2017

Chemistry A European J

155

139

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Building Heterocyclic Systems with RC(OR)₂⁺ Carbocations in Recyclable Brønsted Acidic Ionic Liquids: Facile Synthesis of 1‐Substituted 1H‐1,2,3,4‐Tetrazoles, Benzazoles and Other Ring Systems with CH(OEt)₃ and EtC(OEt)₃ in [EtNH₃][NO₃] and [PMIM(SO₃H)][OTf]

Aridoss

Laali

2011

Eur J Org Chem

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Abstract1‐Aryl/alkyl‐1H‐1,2,3,4‐tetrazoles can conveniently be synthesized in one‐pot reactions from the corresponding amines by reaction with TMSN3 and CH(OEt)3 using the readily available, recyclable, Brønsted acidic ionic liquids [EtNH3][NO3] IL‐1 and [PMIM(SO3 H)][OTf] IL‐2 under mild conditions in high yields. Based on comparative reactions, whereas both ILs are excellent promoters, reactions are completed with shorter reaction times and in higher yields with IL‐2. Among 24 examples provided, identical products were obtained via the two ILs, except in the case of 2‐aminobenzoic acid where tetrazole was formed with IL‐2 and 2‐ethylquinazolin‐4(3H)‐one was formed with IL‐1. By leaving out TMS‐N3 from the reaction, the in‐situ formed CH(OEt)2+ and EtC(OEt)2+ (via their corresponding orthoesters) react under sonication with o‐phenylenediamine bearing various substituents, o‐aminothiophenol and o‐aminophenol to form a wide array of benzazoles (benzimidazole, benzothiazole and benzoxazole) and quinazolin‐4(3H)‐one in high yields (18 examples). The two ILs reacted differently in reaction with 2‐aminobenzamide, whereas quinazolin‐4(3H)one was formed with IL‐2/CH(OEt)3, the “unexpected” N‐ethylquinazolin‐4(3H)one was isolated with IL‐1/CH(OEt)3. The latter was also formed from 2‐aminobenzoic acid in IL‐1/CH(OEt)3. Mechanistic implications are addressed. The reported protocols enable rapid assembly of a host of heterocyclic systems in high yields with the added advantage of recycling and re‐use of the ILs.

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Synthesis of arylated norbornyl amino acid esters

et al. 2010

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Synthesis of novel fluorophenylaryl / heteroaryl ether derivatives

Cited by 4 publications

References 3 publications

Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram‐Positive Directed Antibacterial Effects

Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram‐Positive Directed Antibacterial Effects

Building Heterocyclic Systems with RC(OR)₂⁺ Carbocations in Recyclable Brønsted Acidic Ionic Liquids: Facile Synthesis of 1‐Substituted 1H‐1,2,3,4‐Tetrazoles, Benzazoles and Other Ring Systems with CH(OEt)₃ and EtC(OEt)₃ in [EtNH₃][NO₃] and [PMIM(SO₃H)][OTf]

Synthesis of arylated norbornyl amino acid esters

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Synthesis of novel fluorophenylaryl / heteroaryl ether derivatives

Cited by 4 publications

References 3 publications

Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram‐Positive Directed Antibacterial Effects

Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram‐Positive Directed Antibacterial Effects

Building Heterocyclic Systems with RC(OR)2+ Carbocations in Recyclable Brønsted Acidic Ionic Liquids: Facile Synthesis of 1‐Substituted 1H‐1,2,3,4‐Tetrazoles, Benzazoles and Other Ring Systems with CH(OEt)3 and EtC(OEt)3 in [EtNH3][NO3] and [PMIM(SO3H)][OTf]

Synthesis of arylated norbornyl amino acid esters

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Product

Resources

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Building Heterocyclic Systems with RC(OR)₂⁺ Carbocations in Recyclable Brønsted Acidic Ionic Liquids: Facile Synthesis of 1‐Substituted 1H‐1,2,3,4‐Tetrazoles, Benzazoles and Other Ring Systems with CH(OEt)₃ and EtC(OEt)₃ in [EtNH₃][NO₃] and [PMIM(SO₃H)][OTf]