Collect. Czech. Chem. Commun. 2011, 76, 957-988
Published online 2011-07-07 13:16:17

Sugar-modified derivatives of cytostatic 6-(het)aryl-7-deazapurine nucleosides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides

Petr Nauš, Pavla Perlíková, Radek Pohl and Michal Hocek*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleosides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides bearing an alkyl, aryl and hetaryl group in position 6 were prepared by palladium catalyzed cross-coupling reactions of corresponding (protected) 6-chloro-(7-fluoro)-7-deazapurine nucleosides with (het)arylboronic, hetarylstannanes and trimethylaluminium eventually followed by deprotection. Key intermediate 6-chloro-7-deazapurine 2′-C-methyl-β-D-ribofuranoside was prepared via a stereoselective nucleobase anion glycosylation with toluoyl-protected 1,2-anhydro-2-C-methylribofuranose. The 1,2-anhydro sugar was synthesized in 3 steps starting from readily available 2-C-methylribonolactone. The 6-chloro-7-deazapurine arabinofuranoside intermediate was obtained by epimerization from 3′,5′-protected 6-chloro-7-deazapurine ribofuranoside via 2′-hydroxyl oxidation followed by reduction. None of the prepared compounds showed any considerable cytostatic or antiviral activity.

Keywords: Nucleosides; Cross-coupling; Antitumor agents; Purines; 7-Deazapurines; 7H-Pyrrolo[2,3-d]pyrimidine; Cytostatic agents.

References: 39 live references.