N-7-DNA - SYNTHESIS AND BASE PAIRING OF OLIGONUCLEOTIDES CONTAINING 7-(2-DEOXY-BETA-D-ERYTHRO-PENTOFURANOSYL)ADENINE (N(7)A(D))

Abstract

The synthesis of oligonucleotides containing 7-(2-deoxy-beta-D-erythro-pentofuranosyl)adenine (N(7)A(d); 1) is described. Compound 1 was obtained from the precursor 4-amino-1H-imidazole-5-carbonitrile 2-deoxyribonucleoside 6 and was found to be much more labile than A(d). The N-6-benzoyl protecting group (see 8) destabilized the N-glycosylic bond further and was difficult to remove by NH3-catalyzed hydrolysis. Therefore, a (dimethyl-amino)methylidene residue was introduced (--> 9). Amidine 9 was blocked at OH-C(5') with the dimethoxytrityl residue ((MeO)(2)Tr), and phosphonate 4 as well as phosphoramidite 5 were prepared under standard conditions. Phosphonate 4 was employed in solid-phase oligonucleotide synthesis. Homooligonucleotides as well as self-complementary oligonucleotides were prepared. The oligomer d[(N(7)A)(11)-A] (11) formed a duplex with d(T-12) (13). Antiparallel chain polarity and reverse Watson-Crick base pairing was deduced from duplex formation of the self-complementary d[(N(7)A)(8)-T-8] (14).