An Efficient Synthesis of Novel 3-[(Heteroaryl-2-ylimino)-methyl]-4-hydroxy-chromen-2-ones and Analogue of Tetrazole Derivatives and Their Antibacterial Activity

Ramiz Hoti,Agon Bytyqi,Gjyle Mulliqi-Osmani,Malësore Pllana-Zeqiri,Hamit Ismaili,Veprim Thaçi

doi:10.3390/m1303

Ramiz Hoti, Agon Bytyqi + Show 4 more

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https://doi.org/10.3390/m1303

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Abstract

Synthesis of a series of the substituted [(pyridinyl and pyrimidin-2-ylimino)-ethyl]-4-hydroxy-chromen-2-ones and their tetrazole derivates is presented in this study. By catalytic condensation of 4-hydroxy-3-acetylcoumarine 2 and 2-aminopyridines 3(a-d), 3-[(pyridin-2-ylimino)-ethyl]-4-hydroxy-chromen-2-ones 4(a-d) are synthesized in high yield. During the condensation reaction of 2 and 4-amino-2,6-dihydroxypyrimidine 3e, 3-[1-(2,6-Dihydroxy-pyrimidin-4-ylimino)-ethyl]-4-hydroxy-chromen-2-one 4e as condensation products is synthesized. In following series, by cyclization reactions of compounds 4 (a-e) with sodium azide, analogue 3-substituted pyridin-2-yl and pyrimidin-2-yl-5-methyl-2,5-dihydro-1H-tetrazol-5-yl]-4-hydroxy-chromen-2-one 5(a-e) are synthesized the products. Structural characterization of the synthesized products is done on the basis of spectrometric data. Antibacterial activity of the compounds 4(a-e) and 5(a-e) against S. aureus, E. coli and Klebsiella was examined by measuring the inhibition zones around the disks marked with the corresponding products solution. The impact of substitutions in antimicrobial is also explored. Compounds with polar groups have shown significant antibacterial activity against these microorganisms.

Highlights

Coumarin (2H-Chromen-2-one) derivatives are a large class of oxygen-containing heterocyclic compounds with particular importance
We have previously reported on the synthesis and antibacterial activity of some substituted chromen-2-one derivatives [27,28,29]
The 3-acetyl-4-hydroxycoumarin is synthesized by direct acetylation of 4-hydroxycouma rin with acetic acid in the presence of Phosphorous oxychloride as a catalyst, according to the procedure described in the literature [30]

Summary

Introduction

Coumarin (2H-Chromen-2-one) derivatives are a large class of oxygen-containing heterocyclic compounds with particular importance. Coumarin derivatives first were known as important agents for the treatment and prevention of various diseases [3]. Some naturally occurring coumarins such as novobiocin, chlorobiocin and coumermycin are an unprecedented class of antibiotics, showing expressed activity against Gram-positive bacteria [4]. It was reported that some coumarin analogues exhibited antioxidant [10,11], cytotoxic [12,13] and anti-tubercular activity [14]. A significant number of substituted coumarins show sedative, analgesic, anticoagulant [15], anti-HIV [16,17], antidiabetic [18] and hepatoprotective activity [19]

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