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 c1c'A(d) and dT residues (7 and 8) as well as palindromic oligomers such as d(C-G-C-G-c1c7A-c1C7A-T-T-C-G-C-G) (10) and d(G-T-A-G-c1c7A-c1c7A-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.