Oligonucleotides Containing 8,1′‐Ethano‐2′‐deoxyadenosine: Synthesis and Properties

Abstract

Oligonucleotides containing 8,1′‐ethano‐2′‐deoxyadenosine (ethano‐dA) were synthesized in which the adenine base (^ethA) is fixed in the syn conformation. Ethano‐dA phosphoramidite was synthesized by using a 1,5‐hydrogen‐atom transfer/radical cyclization process and introduced into oligonucleotides, which were successfully obtained by employing the 4,4′‐dimethoxytrityl‐off synthesis mode. The duplex‐forming ability of the oligonucleotides containing ethano‐dA was evaluated. In the antiparallel Watson–Crick duplex, the ^ethA formed stable base pairs with thymine and guanine, in which two Hoogsteen‐type hydrogen bonds could be formed. By contrast, the parallel Hoogsteen duplex containing the ^ethA:thymine base pair showed thermal stability comparable to that containing a natural adenine:thymine base pair because ^ethA and thymine can form two Watson–Crick‐type hydrogen bonds. These results indicated that ethano‐dA may be helpful for elucidating the function of adenine bases through the syn conformation in DNA.