6'-Carbon-substituted carbocyclic analogs of 2'-deoxyribonucleosides - Synthesis and effect on DNA/RNA duplex stability

Article abstract of DOI:10.1016/0040-4020(96)00755-7

6'-α-Methyl and 6'-α-hydroxymethyl carbocyclic thymidines 11 and 22 have been synthesized via bicyclic lactone 2 and amines 9 and 19, respectively, as key intermediates. Both nucleoside analogs were subsequently elaborated into 5'-O-DMTr protected 3'-phosphoramidites of 6'-α-methyl and 6'-α-hydroxymethyl carbocyclic thymidines as well as appropriately base protected 5-methyl 2'-deoxycytidines. Analysis of the RNA-binding affinity of modified oligodeoxyribonucleotides incorporating these 6'-substituted carbocyclic nucleoside analogs revealed a strongly position dependent effect on DNA/RNA duplex stability. While duplex stability is significantly reduced by point modifications at separated sequence positions, it is only marginally affected by stretches of contiguous modified building blocks.