1,7-Dideaza-2′-deoxyadenosine: Building blocks for solid-phase synthesis and secondary structure of base-modified oligodeoxyribonucleotides

The 1,7-dideaza-2′-deoxyadenosine (c¹c⁷A_d; 1 ) was converted into building blocks 3a , b for solid-phase oligodeoxyribonucleotide synthesis. Testing various N-protecting groups – benzoyl, phenoxyacetyl, (fluoren-9-yl)methoxy]carbonyl, and (dimethylamino)methylidene – only the latter two were found to be suitable ( 1 → 4b, d ). Ensuing 4,4′-dimethoxytritylation of 4d and phosphitylation afforded the 3′-phosphonate 3a or the 3′-(2-cyanoethyl)diisopropylphosphoramidite] 3b . Self-complementary oligonucleotides with alternating dA or c¹c⁷A_d and dT residues ( 7 and 8 ) as well as palindromic oligomers such as d(C-G-C-G-c¹c⁷ A-c¹c⁷ A-T-T-C-G-C-G) ( 10 ) and d(G-T-A-G-c¹c⁷ A-c¹c⁷ A-T-T-C-T-A-C) ( 12 ) were synthesized. Duplex stability was decreased because 1 cannot form Watson-Crick or Hoogsteen base pairs if incorporated into oligonucleotides. On the other hand, the structural modifications in 10 and 12 forced these palindromic oligomers to form hairpin structures.