Synthesis of 9-deazapurine derivatives and 1,2,3-triazolyl sulfonamido-ribofuranoside conjugates

Ban, Željka (2015) Synthesis of 9-deazapurine derivatives and 1,2,3-triazolyl sulfonamido-ribofuranoside conjugates. Doctoral thesis, Faculty of Science > Department of Chemistry.

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Abstract

In this doctoral thesis, new C-9 and N-7 substituted derivatives of 9-deazapurine as well as new 1,2,3-triazolyl ribofuranoside conjugates were synthesized as potential inhibitors of purine nucleoside phosphorylase and carbonic anhydrase, respectively. Modified purine nucleobases 9-deazaguanine and 2,6-dichloro-9-deazapurine, and a series of modified ribofuranosides were prepared. Reversed nucleosides were obtained by linking C5 position of ribose to N7 position of 2,6-dichloro-9-deazapurine. They were subsequently transformed to 9-deaza derivates of hypoxanthine, guanine and adenine. 9-ethynyl-9-deazaguanine was synthesized using Sonogashira coupling. By subsequent Cu(I) catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) with sugar azide, 1,2,3-triazolyl conjugate of 9-deazaguanine was obtained. CuAAC reaction is also used for the synthesis of new 1,4-disubstituted 1,2,3-triazolyl ribofuranoside conjugates. The introduction of sulfonamido group at C1 position of the 1,2,3-triazolyl ribofuranoside conjugate or 5-azido ribose is achieved by using various sulfonamides and BF3·Et2O as the catalyst. Reaction was performed in the microwave reactor or by using classical method. The more successful method for the preparation of 1,4-disubstituted 1,2,3-triazolyl sulfonamido-ribofuranoside conjugates includes CuAAC cycloaddition of 5-azido-1-sulfonamido-ribofuranosides and 1-O-propargyl ribose. In the same manner, 1,4-disubstituted 5'-iodouracil triazole conjugates were synthesized using propargyl derivative of 5'-iodouracil reversed nucleoside and 5-azido derivative of ribose. Selected compounds were tested for the antiproliferative activity on the panel of eight cell lines (MDCK, HeLa, CaCO-2, NCI-H358, K562, Jurkat, HuT 78 and Raji).

Item Type: Thesis (Doctoral thesis)
Keywords: reversed nucleosides, purine nucleoside phosphorylase, carbonic anhydrase, 1,2,3-triazolyl conjugates, 9-deazaguanine
Supervisor: Žinić, Biserka
Date: 2015
Number of Pages: 171
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Branka Maravic
Date Deposited: 15 May 2015 10:11
Last Modified: 15 May 2015 10:11
URI: http://digre.pmf.unizg.hr/id/eprint/3989

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