DNA containing side chains with terminal triple bonds: Base-pair stability and functionalization of alkynylated pyrimidines and 7-deazapurines

The synthesis of a series of oligonucleotides containing 5-substituted pyrimidines as well as 7-substituted 7-deazapurines bearing diyne groups with terminal triple bonds is reported. The modified nucleosides were prepared from the corresponding iodo nucleosides and diynes by the Sonogashira cross-coupling reaction. They were converted into phosphoramidites and employed in solid-phase synthesis of oligonucleotides. The effect of the diyne modifications on the duplex stability was investigated. The modified nucleosides were used for further functionalization using the protocol of Huisgen-Sharpless [2 + 3] cycloaddition ('click chemistry').