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Synthesis 2010(23): 4119-4130  
DOI: 10.1055/s-0030-1258271
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Two Convergent Approaches toward Novel Carbocyclic C-Nucleosides

Radim Nencka, Michal Šála, Milan Dejmek, Martin Dračínský, Antonín Holý, Hubert Hřebabecký*
Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic, v.v.i., Gilead Sciences & IOCB Research Center, 166 10 Prague 6, Czech Republic
Fax: +420(2)20183560; e-Mail: nencka@uochb.cas.cz;
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Publication History

Received 3 August 2010
Publication Date:
28 September 2010 (online)

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Abstract

Two convergent methodologies for construction of novel carbocyclic C-nucleosides allowing the syntheses of derivatives with uracil heterobase substituted at the position C-5 as well as C-6 were developed. The crucial step of the first methodology was the reaction of (6-chloro-2,4-dimethoxypyrimidin-5-yl)lithium, the nucleobase precursor, with suitable ketones, the carbocyclic pseudosugar precursors. The second approach was based on the copper-catalyzed cross-coupling between magnesiated pyrimidine and appropriate allyl chlorides. These methodologies were applied for the synthesis of novel carbocyclic C-nucleosides bearing cyclohexene or cyclohexane as a pseudosugar.

Key words

carbocyclic C-nucleosides - convergent approach - uracil - pyrimidines - cross-coupling reaction

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