Collect. Czech. Chem. Commun. 2004, 69, 1955-1970

Covalent Analogues of DNA Base-Pairs and Triplets VII. Synthesis and Cytostatic Activity of Bis(purin-6-yl)acetylene and -diacetylene Nucleosides

Petr Nauš, Ivan Votruba and Michal Hocek*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-166 10 Prague, Czech Republic


The title bis(purin-6-yl)acetylene and -diacetylene nucleoside derivatives were prepared as covalent base-pair analogues starting from acyl-protected 6-ethynylpurine and 6-iodopurine nucleosides by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by deprotection. The key starting acyl-protected 6-ethynylpurine nucleosides were prepared by a sequence of cross-coupling reactions of protected 6-halopurine nucleosides with (trimethylsilyl)acetylene followed by a modified desilylation with TBAF in presence of acetic acid. Surprisingly, the acyl-protected nucleosides exhibited significant cytostatic activity higher than the fully deprotected title compounds.

Keywords: Purines; Nucleobases; Nucleosides; Base-pairs; Alkynes; Cross-coupling reactions; Protecting groups; Desilylation; Oxidative dimerization; Cytostatics.

References: 37 live references.