Here, we present efficient syntheses of the R and S diastereomers of 8,5'-cyclo-2'-deoxyadenosine and 6,5'-cyclo-2'-deoxyuridine. We incorporated these interesting nucleosides into DNA to study how the cyclo linkage affects the stability of duplex formation.

A concise synthesis of both C5 0 diastereomers of 5 0 -(hydroxymethyl)-6,5 0 -cyclo-2 0 ,5 0 -dideoxyuridine is presented. Individual crystal structures of the fully deprotected S-and R-stereoisomers indicate that the addition of a methylene group between the C5 0 and O5 0 positions of 6,5 0 -cyclo-2 0 -deoxyuridine increases the distance between the nucleobase and backbone. The resulting nucleosides adopt a conformation that more closely mimics A-form rather than B-form nucleotides. Nucleotides of 5 0 (R)-(hydroxymethyl)-6,5 0 -cyclo-2 0 ,5 0 -dideoxyuridine were successfully incorporated into DNA oligonucleotides during automated synthesis, but full-length oligonucleotides were not obtained after post-synthetic cleavage from the solid support due to a base-catalyzed strand cleavage at the site of insertion.