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Synthesis 2009(16): 2689-2696  
DOI: 10.1055/s-0029-1216882
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis and Chemoselective N- and O-Alkylation of Thiadiazolopyrimidine Nucleosides and Uridines

Abugafar M. L. Hossion, Rafiqul Islam, Rafiya K. Kandahary, Tomohisa Nagamatsu*
Department of Drug Discovery and Development, Division of Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayma University, 1-1-1, Tsushima-Naka, Okayama 700-8530, Japan
Fax: +81(86)2517926; e-Mail: nagamatsu@pheasant.pharm.okayama-u.ac.jp;
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Publication History

Received 18 March 2009
Publication Date:
01 July 2009 (online)

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Abstract

A facile and selective N- or O-alkylation of 4-β-d-ribofuranosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione as well as uridines was accomplished via bimolecular base alkylation or bimolecular nucleophilic substitution reaction controlled by the reagents. In the presence of 18-crown-6 and anhydrous K2CO3, the highly chemoselective O-methylation was performed using dimethyl carbonate (DMC) in DMF at 22-25 ˚C, i.e. the 2′,3′-O-isopropylidene derivatives of 4-β-d-ribofurnosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione, uridine, and 5-bromouridine, underwent only the primary alcoholic O-methylation reaction without affecting the NH group of the pyrimidne ring. The novel N-alkylated derivatives of 4-β-d-ribofurnosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione were also prepared using the appropriate alkyl halides with a base.

Key words

ribofuranosylthiadiazolopyrimidines - uridines - chemo­-selectivity - alkylations - heterocycles