Synthesis of New Derivatives of Heterocyclic Systems Containing Triazolopyrimidine, thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b] thiazine Moiety Showing Promising Antimicrobial Activity

Author(s): Samvel N. Sirakanyan*, Domenico Spinelli*, Athina Geronikaki, Viktor A. Kartsev, Elmira K. Hakobyan, Anush A. Hovakimyan.

Journal Name: Current Organic Chemistry

Volume 22 , Issue 26 , 2018

Graphical Abstract:


Background and Objective: Continuing our research in the field of heterocyclic compounds and exploiting our experience in the synthesis of pyridothieno(furo)[3,2- d]pyrimidine derivatives decorated by suitable reactive groups (in turn able to give rise to the formation of new heterocyclic rings), we now carried out a research with the aim of building in different position of the pyrimidine some new hetero-rings: the 1,3,4-triazole, thiazole and thiazine. Moreover their possible antimicrobial activity against some grampositive and gram-negative bacilli strains has been evaluated.

Methods: Starting from the hydrazino derivative of pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines 2 (7) by reflux with triethyl orthoformate or formic acid, some substituted isomeric pyrido[3',2':4,5]thieno(furo)[2,3-e][1,2,4]triazolopyrimidines 3 and 4 (10) have been synthesized. By alkylation of compounds 8 with alkyl dichlorides, the cyclization to a thiazoline or to a thiazine ring on the [a] side of the pyrimidine ring occurs, with the formation of the new pentacyclic systems: pyrido[3',2':4,5]thieno[ 3,2-d][1,3]thiazolo[3,2-a]pyrimidin-7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1- b][1,3]thiazin-7(8)-ones 16.

Results: 11-Alkyl(aryl)-8,8-dimethyl-7,10-dihydro-8H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4] triazolo[4,3-c]pyrimidines 3 gave a Dimroth rearrangement in acidic media. It was observed that the cyclization of compounds 7 and 8 occurred linearly with the expected formation of pyrido[3',2':4,5]thieno(furo)[3,2- d][1,2,4]triazolo[4,3-a]pyrimidin-7(8)-ones 10 and pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin- 7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-7(8)-ones 16: that is triazole, thiazole and thiazine ring condensation occurs at the [b] side of the pyrimidine ring. During the alkylation of compounds 7, the unusual cleavage of the hydrazino group took place with the formation of 8(9)- methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12.

Conclusion: The synthesis of some new ‘complex’ pentaheterocyclic systems containing triazolopyrimidine, thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b]thiazine moiety based on the pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines is described. During the alkylation of 9(10)-hydrazinopyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidin-7(8)-ones 7 an unexpected cleavage of the hydrazino group has been observed with the formation of 8(9)-methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12. Biological tests on the newly synthesized compounds evidenced that some of them showed promising antimicrobial activity.

Keywords: Triazolopyrimidine, thiazolo[3, 2-a]pyrimidine, pyrimido[2, 1-b]thiazine, cyclization, alkylation, antimicrobial activity.

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Article Details

Year: 2018
Page: [2576 - 2588]
Pages: 13
DOI: 10.2174/1385272822666181122111339
Price: $58

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